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Int J Artif Organs 2010 ; 33 ( 7): 445

Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia

Poster Sessions

Cardiovascular Miscellaneous, 446

Cardiovascular Modeling and Simulation, 448
Apheresis, 451
Tissue Engineering 1, 453
Tissue Engineering 2, 456
Artificial Pancreas, 458
Hemodialysis 1, 459
Hemodialysis 2, 461
Artificial Kidney 1, 464
Vascular and Biomaterials, 466
Cardiovascular Device Engineering, 469
Cardiac Clinical, 472
Transplantation, 474
Artificial Liver, 477
Polymeric Biomaterials, 478
Biomaterials, 480
Artificial Kidney 2, 483
Hemodialysis 3, 485
Hemodialysis 4, 487

This abstract book has been produced electronically by Wichtig Editore Medical Publisher and is also available on the Journal’s
web site at www.artificial-organs.com

Every effort has been made to faithfully reproduce the abstracts as submitted. However, no responsibility is assumed by the
organisers as well as by the Publisher for any injury and/or damage to persons or property as a matter of products liability,
negligence or otherwise, or from any use or operation of any methods, products, instructions or ideas contained in the mate-
rial herein. Because of the rapid advances in the medical sciences, we recommend that independent verification of diagnoses
and drug dosages should be made.

© 2010 Wichtig Editore - ISSN 0391-3988 445

Int J Artif Organs 2010 ; 33 ( 7): 446- 490
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
Cardiovascular miscellaneous
P1 (144)
EFFECT OF CARDIOPLEGIA ON RBC DEFORMABILITY AND ABILITY TO
DELIVER OXYGEN
K.H. Son1, C.B. Ahn2, I.S. Noh3, E.K. Shin3, M.J. So3, H.A. Kim3, K.T. Kim1,
S.H. Lee1
1
Department of Thoracic and Cardiovascular Surgery, College of Medicine,
Korea University, Seoul, Korea; 2Korean Artificial Organ Center, Seoul, Korea;
3
Department of Chemical Engineering, Seoul National University of Technology,
Seoul, Korea
Objectives: The advantage of blood cardioplegia is superior oxygen-
carrying capacity, better osmotic properties, and antioxidants than crystalloid
counterpart. Hyperkalemic cardioplegia has adverse effects on hemorheology.
Hyperkalemia is known to decrease RBC deformability which is essential for
tissue perfusion. As far as we know, there have been no studies on blood
cardioplegia-induced hemorheologic changes. The purpose of this study was to
measure RBC deformability and O2 delivery capacity changes in various blood
cardioplegia.
Methods: Blood from eight healthy volunteers was used. Each sample (100
mL) was divided into 6 groups of 16 mL, and blood cardioplegia was made
according to the following formulas.
Group STH: 4:1 mixture of oxygenated blood with St. Thomas II cardioplegic
solution; Group NS: blood + NS 10 ml/1 L blood; Group K: blood + KCl 20
mEq/1 L blood; Group D: blood + KCl 20 mEq/1 L blood + diltiazem 150 μg/
kg/1L blood; Group A: blood + KCl 20 mEq/1 L blood + adenosine 1 mmol/L L
blood; Group E: blood + KCl 20 mEq/1 L blood + Neutrophil elastase inhibitor
(Sivelestat) 1 mg/1 L blood.
All samples were incubated at a temperature of 8°C (identical to the temperature
used in clinical situations) for 10 minutes. Then, blood samples were prepared to
measure deformability, NO level, 2,3-DPG, and ATP.
Results: There was no statistically significant difference (p=0.984) in deformability
(STH: 0.285±0.02, NS; 0.2862±0.03, K; 0.2781±0.037, D; 0.2793±0.025, A;
0.2775±0.037, E; 0.2847±0.03). The NO levels (STH: 0.012±0.006 nmol/μL, NS;
0.015±0.008 nmol/μL, K; 0.015±0.007 nmol/μL, D; 0.015±0.007 nmol/μL, A;
0.013±0.005 nmol/μL, E; 0.015±0.007 nmol/μL) were not statistically significantly
different (p=0.831). 2,3-DPG levels (STH: 20.33±7.17 nmol/μL, NS;18.80±9.47
nmol/μL, K; 14.69±2.35nmol/μL, D; 15.94±2.31 nmol/μL, A; 12.25±5.69 nmol/μL,
E; 12.57±7.06 nmol/μL) showed no statistically significant difference (p=0.108).
ATP levels (STH: 0.113±0.0.02 nmol/μL, NS; 0.119±0.06 nmol/μL, K; 0.114±0.005
nmol/μL, D; 0.147±0.005 nmol/μL, A; 0.163±0.006 nmol/μL, E; 0.158±0.007 nmol/
μL) were not statistically significantly different (p=0.233).
Conclusions: Difference in components of hyperkalemic blood cardioplegia did
not have a significant effect on deformability and oxygen delivery.
P2 (260)
A HYBRID MOCK CIRCULATORY SYSTEM FOR CARDIOVASCULAR
ASSIST DEVICE VALIDATION
S.J. Cheng, P-L Hsu, R.A. McMahon
Department of Engineering, University of Cambridge, Cambridge, UK
Mock circulatory system (MCS) validation of cardiovascular assist devices
(CADs), such as axial blood pumps, is an important process for successful
development of a device. Since the application domain of these “high-risk”
devices is not accessible for ethical and safety reasons until a late stage of
development, accurate MCSs have an integral role in assessing the device’s
performance, longevity and safety. Furthermore, with increasing diversity
in intended sites of operation of CADs, a testing system with versatility and
robustness becomes more important. The authors report on the implementation
of a hybrid MCS with an afterload sensitive left ventricle simulator and numerical
as well as physical elements interacting via electric-hydraulic interfaces.
The MCS consists of adjustable, passive compliance chambers and resistance
elements following the windkessel model. A compact servo-motor driven piston
pump was specially designed to reproduce physiologically correct pressures
and stroke volumes for the left ventricle. In addition, afterload sensitivity was
achieved using a pressure sensor and microprocessor controller, allowing the
real-time acute interaction between the MCS and CADs. The mitral and aortic
valve functions were reproduced by two commercially available mechanical
heart valves. In order to test intra-aortic devices, separate ascending and
descending aortic sections were built. Other systemic components were
numerically simulated via a previously published computer model with pressure
input data from physical components.
446 © 2010 Wichtig Editore - ISSN 0391-3988
The hemodynamics of various physiological conditions can be reproduced in
the MCS by adjusting the stroke length and speed of the piston pump. The
piston pump is capable of generating flow rates of 2 to 10 l/min with heart rates
up to 130 bpm. Results closely mimic physiological conditions for rest, exercise,
and heart failure conditions. The new hybrid MCS provides a valuable tool for
the development of CADs placed in various aortic sites, potentially shortening
the time required for animal and clinical trials.
P3 (212)
TAVI hemodynamics: relevant bioengineering and fluid
dynamical problems
G. D’Avenio, S. Donatiello, C. Daniele, M. Grigioni
Department of Technology and Health, Istituto Superiore di Sanità, Rome, Italy
Objectives: The percutaneous valve (PV) is an implantable device, noninvasively
put inside a native or bioprosthetic calcified valve, thus in a not optimal annulus
with persistent rigid structures. Leakage flows and forward flow structures with
abnormal pressure gradients could be relevant for the quality of life of implanted
patients.
From a bioengineering point of view, flow structures and pressure drop depend
on the shape imparted perioperatively to the PV, due to its conformability. In
the past, patient-valve mismatch was related to bioengineering elements, which
were sometimes easily controllable by clinicians: e.g., appropriate valve sizing.
PVs are devices made more rigid than a conventional bioprosthesis due to the
presence of the stent. Thus, the orifice area of the PV can not vary as much as
a bioprosthesis with the transvalvular pressure. This hints that flow separation
occurs more easily, similarly to a rigid orifice. Moreover, the pressure recovery
distal to the vena contracta could be influenced by the shape of the outflow
region of the PV. The aim of the study is to highlight the possible consequences
of the procedures followed by clinicians during TAVI (Transcutaneous Aortic
Valve Implantation).
Methods: Numerical fluid dynamics analyses were carried out for assessing
the role of the outflow tract as for the hemodynamics, and to demonstrate the
relevance of conformability during implantation.
Results: The size of the vena contracta was found to be dependent on several
factors, such as the presence of vortical structures. Changes in hemodynamic
parameters depend on the final set-up of the PV at the site of implantation.
Conclusions: The increasing success of TAVI can overshadow the fact that
the clinicians often make an off-label use of devices (e.g., stents), which can
have dangerous consequences, or at least be non-optimal for the patient. Any
change in the device use should be authorized by the manufacturer and its
Notified Body, in order to assure safety and efficacy of the device.
P4 (38)
HYDRODYNAMIC ANALYSIS OF NEW GENERATION DISPERSIVE
PERFUSION CANNULAE
W. Fukuda, I. Fukuda, M. Minakawa, K. Daitoku, Y. Suzuki, K. Fukui, T. Inamura,
M. Shirota
Thoracic and Cardiovascular Surgery, Hirosaki University Graduate School of
Medicine, Department of Intelligent Machines and System Engineering, Faculty
of Science and Technology, Hirosaki University, Hirosaki, Aomori, Japan
Background and Objectives: New generation dispersive perfusion cannulae
were developed to attenuate flow in the aorta and avoid atheroembolism due to
jet flow. The objective of this study was to evaluate and compare the magnitude
of flow velocity and distribution of shear stress in the experimental aortic models
using different types of cannulae.
Materials and Methods: Hydrodynamic analysis of aortic cannulation (normal
direction and root direction) was performed using particle image velocimetry in
glass aortic perfusion models. Five different types of cannulae, Endhole (EH),
Dispersion (DSP), Softflow (SFT), EzGlide (EZG), and Stealthflow (STL), were
tested in three-dimensional normal aortic model and aneurysm model. Flow
velocity, stream line, distribution of shear stress were analyzed.
Results: In the normal model, the flow from the EH cannula went straight to
the greater curvature and the rapid flow collided to ostium of the arch vessels
without deceleration (Table). The distribution of shear stress was great along the
grater curvature of the aortic arch. In dispersive cannulae, decelarated flow was
observed at the cannula exit and the maximal shear stress appeared on the lesser
curvature. When the cannula tip was directed toward the aortic root, the flow
velocity was as slow as 0.1m/sec in the aortic arch. In aneurysm model, rapid
flow from the EH cannula hit the aneurysmal wall, creating counterclockwise
vortex and it went into the arch vessels. In dispersive cannulae, a small vortex
was observed in the proximal aortic arch but no backflow from the aneurysm
dorm went into the arch vessels.
Int J Artif Organs 2010 ; 33 ( 7): 447
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
Conclusions: In new generation dispersive cannulae, flow in the aortic arch was
soft and shear stress was small in the ascending aorta. Decreasing sandblast
effect of jet flow from the cannula tip is important to prevent postoperative
embolic stroke in cardiac surgery.
P5 (109)
Hall effect in blood flow measurements
M. Szwast, W. Piatkiewicz
Department of Chemical and Process Engineering WUT, Warsaw, Poland
Controlling of proper blood flow in case of artificial heart based on centrifugal
pumps is extremely important for its successful application. Measurement
devices shouldn’t disrupt blood flow and should be non-invasive.
The application of Hall effect in order to measure blood flow velocity was
proposed due to electrolyte properties of the blood plasma.
A device including constant magnetic field source (0,5 T), silver electrodes
(diameter 1 mm) and digital voltmeter (HIOKI digital hightester 3237) connected
with personal computer was used. Data were recorded by LabView software.
Studies were performed on NaCl electrolyte in different concentration, different
flows and different magnetic field polarization. Results were obtained as a Hall
voltage versus time.
Measured voltage was very stable in time and was on the level of milivolts.
Magnetic field polarization influenced only on voltage polarization, but not
on absolute value. It was proved that flow velocity results are independent of
electricity carriers’ concentration. However, what is very important, the linear
relationship between flow and Hall voltage was proved.
P6 (300)
DEVELOPMENT OF A TOROIDAL CONVOLUTION PUMP FOR EMERGENCY
LIFE SUPPORT SYSTEM
I. Saito1, I. Nemoto2, T. Isoyama1, T. Ono1, H. Nakagawa1, W. Shi1, Y. Inoue1,
K. Ishii1, Y. Abe1
1
Department of Biomedical Engineering, Graduate School of Medicine, The
University of Tokyo, Tokyo, Japan; 2iMed Japan Inc, Chiba, Japan
Objectives: Although the percutaneous cardiopulmonary support (PCPS) is
very useful to survive the cardiopulmonary arrest, the PCPS is not widely used
in the emergency medical setting because the PCPS is large and complicate.
We combine an artificial lung, a blood pump, a pump driver and a battery as
an energy source of the pump driver and develop an emergency life support
system (ELSS). Because the junction of the artificial lung and the blood pump
of the ELSS must be simple and smooth for reducing the size, the inlet and
outlet position of the pump is restricted by the artificial lung and the blood
pump position correlation. Although the centrifugal pump is widely used in the
PCPS, the centrifugal pump can’t work as the blood pump of the ELSS because
the inlet and outlet position of the centrifugal pump are strongly restricted. We
develop a suitable blood pump for the ELSS that is named toroidal convolution
pump (TCP).
Methods: The TCP is composed of a rotary vane and housing like the
regenerative pump. The outer shape of the rotary vane is like a bowl. There
are some spokewise slits in the rotary vane for dividing inner area of the rotary
vane. By rotating the vane of the TCP, the blood in each area separated with
the spokewise slits in the vane, is carried from inlet to outlet and convolute in
each area.
The pump performance of the TCP was measured on the mock circulation
system with saline as test fluid. We also performed hemolysis test of the
TCP on condition that the pump flow and head are 5 l/min and 100 mmHg,
respectively.
Results: The TCP can generate 8 l/min against 500 mmHg on the condition
that the pump revolution speed is 1600 rpm and 5 l/min against 350 mmHg on
the condition that the pump revolution speed is lower than 1300 rpm. The NIH
(Normalized Index of Hemolysis) of the TCP is 0.0017.
Conclusions: The TCP has enough performance as the blood pump of the ELSS.
P7 (63)
MODEL BASED DIAGNOSIS FOR EXTRACORPOREAL MEMBRANE
OXYGENATION
A. Stollenwerk1, J. Jörgens1, J. Arens2, M. Walter3, R. Kopp4, S. Kowalewski1
1
Embedded Software Laboratory; 2Dept. of Applied Medical Engineering;
3
Philips Chair of Medical Information Technology; 4Clinic of Operative Intensive
Care 1-4RWTH Aachen University, Aachen, Germany
Objectives: During the application of a state-of-the-art ECMO there are many
reasons for manual supervision in the ICU. Therefore, one reason is the duration
© 2010 Wichtig Editore - ISSN 0391-3988
of the treatment, which often exceeds the lifespan of some components,
especially that of the oxygenator. This leads to the demand of supervision
of the components’ wear-out. The aim of this work is the development of a
model-based diagnosis routine (MBD) of the oxygenator in order to predict the
functionality and wear level during operation.
Materials and Methods: MBD in general uses a model of the physical and
physiological behavior of a system to determine whether a system works as
intended. In this work a mathematical model of the gas exchange is used to
diagnose malfunction and wear-out of the oxygenator. A multi-compartment
model using gas, plasma and hemoglobin phases simulates the dynamics of
O2 and CO2 diffusion as well as the binding of these to hemoglobin. Significant
divergences from measured values indicate the wear level of the oxygenator.
Measured values of an online blood gas analyzer (OBGA), a blood pump and a
gas blender are available for calculation. The model validation is based on the
measured values of animal experiments (n=4, mini-pigs, mean 48 kg), each with
a Medos HILITE 7000 oxygenator.
Results: For all animal experiments the model shows good correlation.
The mean deviation is 15 mmHg, the standard deviation is 26 mmHg. On a
percentage basis the mean error is 6.5% overall and 80 mmHg.
Conclusions: The MBD for the oxygenator works reliably. Oxygenating
failures (like abnormal wearing) can be detected within 25 seconds at the
latest by observing the first derivate of the wear level variable. Replacement
of the oxygenator can be done demand-actuated based on the wear level
observation.
Acknowledgements: The authors gratefully acknowledge the contribution of
the German Research Foundation DFG.
P8 (108)
Microcapillary aspiration as a method of RBC stamina
measurements
M. Szwast, W. Piatkiewicz
Department of Chemical and Process Engineering WUT, Warsaw, Poland
Hemolysis level is an important issue while dealing with artificial organs,
particularly with artificial heart. There are many literature data concerning RBC
stamina; most of them were obtained by shearing in viscosimeters. We have
proposed other method – straining by micropipette aspiration.
Experimental research were done for human RBC using glass microcapillaries,
which diameters were 0.2 – 1 μm, while average RBC’s diameter was 7 μm.
Using our mathematical model, which describes cell aspiration process,
experimental results were elaborated.
Due to different age of tested RBC, experiments were conducted with randomly
chosen RBC collection. The applied stresses were classified as a totally
destructive while all tested RBC were destroyed. Obtained results are higher
comparing to the published one. Literature data show the beginning of the
potentially dangerous range, while our results show the upper border line.
P9 (261)
AN INNOVATIVE METHOD EVALUATING THE DIFFUSIVITY OF HOLLOW
FIBERS
H. Tabesh1,2, A. Khachab1, A. Kashefi1, K. Mottaghy1
1
Institute of Physiology, RWTH Aachen University, Germany; 2Dep. of Biomedical
Eng., Research Center for New Technologies in Life Science Eng., University of
Tehran, Iran
Objectives: Diffusivity is the main parameter concerning membrane’s gas
exchange properties applied e.g. in an oxygenator (artificial lung) where the
diffusion of oxygen molecules from inside to the outside of hollow fibers should
be defined, in accordance with natural lung, by Krogh Diffusion Coefficient
(coef.). Hence, establishing a rapid and comprehensive method to assess this
factor is crucial. Here, in the first step, the diffusion coef. for pure diffusive
silicon fibers is evaluated using an innovative method.
Method: To calculate diffusion coef., a method based on the oxygenation of
liquid and/or gas compartments inside a gas-liquid contactor is developed.
Perflourocarbons (FC), which has high oxygen solubility, is used as the liquid
phase in addition to distilled water. In this system, oxygen flows through hollow
fibers arranged in the contactor filled with FC. After total desoxygenation of FC
and the contactor using nitrogen gas, the oxygen flows inside the fibers with a
defined flow rate. A sensitive oxygen micro-sensor records the partial pressure
of oxygen dissolved in FC continuously till the saturation level. Consequently,
the diffusivity of hollow fibers regarding oxygen is achieved according to Fick’s
first law for diffusion.
Results: The oxygen partial pressure in FC as well as water shows a continuous
elevation till its saturation level. Considering total membrane surface area, wall
447
Int J Artif Organs 2010 ; 33 ( 7): 448
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
thickness and oxygen solubility coef. for FC and water, the diffusion coef. of
employed silicon hollow fibers is calculated of about 50.5e-9 [cm2/sec.cmHg].
Conclusions: The obtained results are highly in accordance with the values
given in the literature applying other methods. Therefore, the proposed method
can be recommended as a rather simple and reliable technique to evaluate the
diffusion coef. of diffusive and micro-porous hollow fibers. However, in the later
case the term permeability coef. is preferred over the term diffusion coef.
P10 (331)
Converting Redy 2000 single bath hemodialysis to an Artificial
Gills Machine
M. W. Elnachef
SIOF Institute, Orange, California, USA
We modified the Redy 2000 which is a single bath hemodialysis machine to
function as a machine that delivers dissolved oxygen in aquatic phase and
remove dissolved carbon dioxide in aquatic phase. The technique is similar to
fish breathing; this is why we call the machine the artificial gills. The dialysate of
the Redy 2000 Machine was replaced by oxygen carrying fluids. Several kinds
of fluids worked successfully. The best were the Ecanow liquid and to a lesser
extent the bovine hemoglobin dimer.
The machine fully oxygenated the blood with a single pass. Oxygen Saturation
went from 73% to 117%. Carbon dioxide removal was a bit more efficient
rendering the oxygenated blood slightly alkalotic. Ph rose from 7.40 to 7.43.
We conclude that the artificial gills machine offers several advantages over
membrane oxygenators that use bubbled oxygen. Dissolved (aquatic) oxygen is
faster to diffuse through the membranes and it is less likely to cause thrombotic
complications. The Redy 2000 Machine is easy to operate and there are
hundreds of thousands of nurses and technicians who know how to operate it.
P11 (68)
EVALUATION OF MECHANICAL PROPERTIES OF IN VIVO TISSUE-
ENGINEERED PROSTHETIC HEART VALVES, “BIOVALVES”
T. Oie1,2, T. Moriwaki1,3, Y. Murayama4, S. Omata4, M. Uechi5, M. Yamanami1,6,
K. Kanda6, Y. Nakayama1,3
1
Department of Bioengineering, National Cardiovascular Center Research
Institute, Osaka; 2Shinkan Kogyo Co., Osaka; 3Graduate School of Chemical
Science and Engineering, Hokkaido University, Sapporo; 4College of
Engineering, Nihon University, Fukushima; 5College of Bioresource Sciences,
Nihon University, Fujisawa; 6Kyoto Prefectural University of Medicine, Kyoto,
Japan
Objectives: We have developed fully autologous valved conduits with sinus,
“Biovalves”, which were prepared in dogs by “in-body tissue architecture”
technology. This study aimed to evaluate mechanical properties of the biovalve
before and after implantation as a pulmonary valve in an animal model.
Methods: Biovalves were obtained by placement of custom-designed molds in
dorsal subcutaneous pouches of beagle dogs for 1 month. Their allogenic- or
auto-implantations were performed as a pulmonary valve. After 3 months of
implantation Biovalves were harvested. The bulk elastic modulus of the conduit,
leaflet, and sinus parts were determined with the force-deformation method,
and the burst pressure was measured with the static water pressure. Scanning
haptic microscope (SHM) was used to obtain a surface elasticity image of a slice
of tissues over 200 × 200 μm area by resolution of less than 2 μm.
Results: Before implantation, the elastic modulus of the sinus of Biovalves was
3.2±0.7 MPa. The minimum burst pressure was 2842.4±1237.8 mmHg, it was
more than ten times of typical blood pressure range in root of pulmonary artery
(approximately 40 mmHg). The SHM image showed the random structure in
Biovalves, whereas the native tissue had multi-layered structure in elasticity.
After implantation, the elastic modulus of the sinus of Biovalves was 2.9±1.2
MPa, The strain at approximately 100 mmHg equivalent loading was 2.5±1.1%
and that of the native tissue was 17.1±1.7%. The SHM images showed random
structure equal to before implantation.
Conclusions: There was no distinguished deterioration of mechanical properties
of the biovalve after implantation, microscopically and macroscopically.
448 © 2010 Wichtig Editore - ISSN 0391-3988
Cardiovascular modeling and simulation
P12 (199)
PUCA PUMP COMPARED WITH IABP: A NUMERICAL MODEL TO STUDY
THEIR HEMODYNAMIC EFFECTS
L. Fresiello1,2, Y.J. Gu3, G. Rakhorst3, A. Di Molfetta1,4, G. Ferrari1
1
IFC, CNR, Rome, Italy; 2Istituto Nazionale per le Ricerche Cardiovascolari,
INRC, Italy; 3Biomedical Eng. and Cardio-thoracic Surg., Univ. Medical Centre,
Groningen, The Netherlands; 4Università degli studi di Roma “Tor Vergata”,
Rome, Italy
Objectives: Aim of this work is to compare the pulsatile catheter pump (PUCA
pump) with the intra-aortic balloon pump (IABP) for different hemodynamic
situations and working conditions.
Materials and Methods: Numerical models for both devices have been
developed and connected to the cardiovascular simulator CARDIOSIM©.
The validation of PUCA pump and IABP models was performed using in vivo
experimental data and literature data, respectively. After validation of the
models, the hemodynamic parameters, such as the cardiac output (CO) and
mean coronary blood flow (CBF) in different hemodynamic conditions were
assessed. For this purpose we considered different values of: left ventricular
systolic elastance (Emaxl= 0.6÷1.8 mmHg∙cm-3), systemic arterial compliance
(Cas=1÷4 cm3∙mmHg-1) and PUCA pump flow (QPUCA=2.75÷5 l/min).
Results: Both numerical models reproduce experimental and literature data
with a good approximation (percentage error <10%). Numerical experiments
evidence that both IABP and PUCA pump performances reduce for higher
values of Emaxl and Cas. IABP shows a higher sensitivity to these parameters
so that in some cases CO does not increase and CBF even drops. PUCA pump,
on the contrary, provides an effective performance in all conditions. On the other
hand, for lower values of Cas, a QPUCA of at least 5 l/min is necessary to assure
CO and CBF increments comparable to those of the IABP.
Conclusions: Numerical models can reproduce the in vivo short-time effects of
any assist device. Moreover, they have the advantages to permit the assessment
of different hemodynamic conditions by simply changing a single parameter in
a given cardiovascular model.
P13 (254)
NUMERICAL MODEL OF “CARDIOCIRCULATORY-LVAD–BAROREFLEX”
SYSTEM: ANALYSIS OF THEIR MUTUAL INTERACTIONS.
L. Fresiello1,2 G. Ferrari1, M.G. Trivella1, A. Di Molfetta1,3, K. Zielin´ski4,
K. Górczyn´ ska4, K.J. Pałko4, M. Kozarski4, M. Darowski4
1
IFC, CNR, Rome, Italy; 2Istituto Nazionale per le Ricerche Cardiovascolari,
INRC, Rome, Italy; 3Università degli studi di Roma Tor Vergata, Roma, Italy;
4
IBBE, PAS, Warsaw, Poland
Objectives: Development of a closed loop control able to simulate the effects
of the baroreflex on the cardiovascular system in presence of a pulsatile left
ventricular assistance device (LVAD).
Methods: The numerical model consists of a cardiovascular simulator,
comprising a pulmonary circulation and arterial circulation (divided into upper
and lower body). It is connected to a set-point model of the cardiopulmonary
and arterial baroreflex. This model can simulate the efferent activity of the
autonomic nervous system on the heart rate (HR), the upper/lower systemic
resistance (Rub/Rlb), the upper/lower venous tone (Vub/Vlb), left/right ventricular
contractility (Els/Ers). All these parameters are changed in order to keep the
systemic arterial pressure (Pas) and the right atrial pressure (Pra) close to the
respective set-point values. In a second step, a LVAD numerical model was
introduced in order to study the interaction of the three systems: cardiovascular
simulator-LVAD-baroreflex.
Results: A heart failure was simulated by reducing the Els to 0.5 mmHg/mL. In
this condition Els and Ers were kept constant while the baroreflex mechanism
caused an increment of HR, Rub, Rlb, and a decrement of Vub and Vlb. In a
second step the LVAD was activated with different flows (QLVAD=1.5-2.6-4.2
l/min) in order to assess its effects on the cardiovascular-baroreflex system. For
higher values of QLVAD, HR, Rub and Rlb decreased while Vub, Vlb, Pas and
Pra increased.
Conclusions: A preliminary validation, based on literature and experimental
data, confirms that the model permits to simulate a pathological condition and
the baroreflex compensatory effects. The LVAD provides an additional flow that
improves the general hemodynamic conditions, and the baroreflex upgrades
its control in order to react to this new circulatory situation. This study will be
continued in the frame of EU Sensorart project.
Int J Artif Organs 2010 ; 33 ( 7): 449
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P14 (169)
CRYOPRESERVATION OF ALGINATE ENCAPSULATED MESENCHYMAL
STROMAL CELLS
A.I. Pravduke, Yu.A. Petrenko, V.P. Grischuk, A.Yu. Petrenko
Institute for problems of cryobiology and cryomedicine, Kharkiv, Ukraine
Cryopreservation is an attractive approach for the long-term storage of
microencapsulated cells, since encapsulation technologies became widely
applied for cell and tissue transplantation, cell delivery and extracorporeal liver
support.
The aim of this study was to investigate the viability, metabolic activity and
differentiation properties of alginate encapsulated mesenchymal stromal
cells (MSC) after cryopreservation using different freezing protocols. MSC
were isolated from human adult bone marrow (in appliance with Ethical
guidelines), expanded in vitro and encapsulated into 1.2% alginate microbeads.
Cryopreservation was carried out under protection of 5% and 10% Me2SO
using three freezing protocols: uncontrolled fast freezing, slow 2-step controlled
freezing with the cooling rate 1°C per min to -80°C, followed by plunging into
LN2 and 3-step controlled freezing with the initial cooling rate 1°C per min to
–40°C, initiation of ice formation at -7°C, followed cooling with 10°C per min
down to -80°C and plunging into LN2. After thawing cell survival within alginate
microbeads was assessed by FDA/EB staining, metabolic activity by Alamar
blue assay. Differentiation capacity of encapsulated MSC was observed after
the addition of specific induction stimuli. It was obtained that the uncontrolled
fast freezing resulted in dramatic decrease of MSC viability. The application of
slow 2-step cooling under protection of 5% and 10% of Me2SO allowed to
achieve MSC viability rates 61±4% and 79±3%, correspondingly. Metabolic
activity of encapsulated MSC cryopreserved with 5% Me2SO decreased in
almost three times, compared to fresh cells, while under protection of 10%
of Me2SO this parameter was 63±2% of control group. The initiation of ice
nucleation during 3-step cooling of encapsulated MSC allowed to increase cell
survival and metabolic activity to 87±2% and 69±4%, correspondingly. Further
studies showed that cryopreserved MSC within alginate microbeads using
slow controlled freezing remained their ability to adipogenic, osteogenic and
chondrogenic differentiation.
P15 (84)
MODELING OF FLOW AND PRESSURE PATTERNS. EVALUATION OF
AN APPROPRIATE PUMP CHAMBER OF VAD FOR DIFFERENT SIZED
PATIenTS
D. Macku, J. Havlik, F. Jezek
Department of Cybernetics, FEE, Czech Technical University in Prague,
Technicka 2, Prague 6, Czech Republic
Objectives: We use MATLAB and Modelica for modeling flow and pressure
patterns in different sized patients. Every patient has his/her unique systemic
vascular bed size and pulmonary vascular bed size. We define vascular bed
parameters for describing the patient’s vascular bed. We acquire vascular bed
data by means of assessment and processing of flow and pressure biosignals.
Methods: Our effort is, for example, to explain the generation of unexpected
arterial hypertension on a pulsatile VAD in extremely small patients, which is
described in the literature. We are able to confirm our hypothesis that different
size vascular bed is adjusted for the appropriate stroke volume of the native
heart. So circulation in different size vascular bed should be supported by the
pump with an appropriate stroke volume. Berlin Heart EXCOR Pediatric has
five pump chamber sizes (10mL, 25mL, 30mL, 50mL and 60mL). The selection
of an appropriate pump chamber size depends on the patient’s size (patient´s
weight). Thoratec VAD uses only one pump chamber size for all patients with
different vascular bed size (65mL). After implantation, all patients have the same
stroke volume - 65mL, and the same average flow during the ejection period,
i.e. 65mL for 300ms (13 l/min!). The average flow for the ejection period, the
average velocity of blood during the ejection period through the entire systemic
and pulmonary circulatory system is higher in non-physiological terms for
extremely small patients and lower in non-physiological terms for extremely
large patients.
Conclusions: Modeling of flow and pressure patterns could help us to better
understand real flow and pressure in the human body. It seems that for the
reliable and safe function of a pulsatile VAD it is necessary to adjust the stroke
volume expelled into ascending aorta or pulmonary artery with regard to the
requirements and parameters of vascular beds.
© 2010 Wichtig Editore - ISSN 0391-3988
P16 (271)
Synchronized pulsatile flow with a continuous flow Left
Ventricular Assist Device
M.C.M. Rutten1, E. Tuzun2, F.N. van de Vosse1, B.A. de Mol1,3
1
Eindhoven University of Technology, The Netherlands; 2Texas Heart Institute,
Houston, TX, USA; 3Academic Medical Centre, Amsterdam, The Netherlands
Because of their durability, continuous flow LVADs have become the devices of
choice in end-stage heart failure treatment. However, one of their drawbacks is
the reduced pulsatility in the circulatory blood pressure and flow. This reduction
in pulse pressure leads to changes in mechanical load on valves and vessels,
and are speculated to cause aortic insufficiency and/or fusion, due to longer
closing times and possibly other vasculatory adverse effects.
To improve the pulsatility of a cf-LVAD, we built a control system, capable of
driving the pump with a sinusoidally varying speed, synchronized with the
heartbeat, in co- and counterpulsating mode. The effect of these pumping
modes were assessed using a mock loop featuring a complete circulation,
including left- and right ventricles of the heart. The ventricles were computer-
controlled to simulate the Frank-Starling mechanism of the heart. Furthermore,
the heart rate in the model depended on blood pressure and therefore was not
constant.
The mock loop was operated to resemble a healty heart, and mild and severe
levels of left ventricular failure. A HeartMate II was used as cf-LVAD, with speeds
varying between 7,000 and 12,000 rpm. Tests at constant pump speed were
done as well.
In all cases, in counterpulsating mode (peak flow in diastole), the maximum flow
through the aortic valve was highest, and so was the opening time of the valve
and stroke volume reduction. In co-pulsating mode, the pressure unloading of
the left ventricle and diastolic volume reduction were the highest.
So, it is possible to drive a cf-LVAD in pulsatile mode, synchronized with the
heartbeat, and to use it either as a counterpulsating or a co-pulsating device.
In counterpulsation, the opening time of the aortic valve is longest, suggesting
better relief of insufficiency risk. On the other hand, co-pulsation leads to a
higher level of pressure and volume unloading, suggesting better circulatory
support for the patient.
P17 (181)
STUDY OF THE HEMODYNAMIC ENERGY CHANGES AFTER CONTROL
ALGORITHM TO IMPROVE FULL-FILLING STATE OF THE BLOOD PUMP
FOR A BELLOE-TYPE PNEUMATIC VENTRICULAR ASSIST DEVICE
C.B. Ahn1,2, K.H. Son1,3, S.H. Lee1,3, J.J. Lee1, J. Choi1, K. Sun1,2,3
1
Korea Artificial Organ Center; 2Brain Korea 21 Project for Medical Science;
3
Department of Thoracic and Cardiovascular Surgery, College of Medicine,
Korea University, Seoul, Korea
Objectives: In a bellows-type electro-pneumatic ventricular assist device, it is
required to maximally maintain full-fill state of the blood sac as less sensitive
to the pressure and resistance conditions of inlet port as possible. A control
algorithm that estimates current filling status and controls pumping motion
variables to maintain full-fill status, has been developed. The concept of the
algorithm is to change the ratio of systole versus diastole times in accordance
with the estimated filling status. Current study is on tests to ascertain the
efficiency of the developed control algorithm in the aspect of the hemodynamic
energy.
Methods: Measurements were performed in terms of hydrodynamic
performance, flow, pressure and the hemodynamic energy equivalents, energy
equivalent pressure (EEP) and surplus hemodynamic energy (SHE). The control
algorithm performance was measured with three control parameters (the time
ratio of systole-diastole, pump rate, and increased inflow resistance) varied. All
the tests were performed with an electro-pneumatic ventricular assist device
developed in our institution, named KH-VAD in a mock loop system with the
afterload pressure fixed to 100 mmHg.
Results: The developed algorithm could adjust the control parameters
automatically to maintain full-filling state of the blood pump in the in vitro
performance test. However the motor speed of VAD was supported with up
to 80% range of inflow resistance. The output flows were increased up to 33%
at the same inflow condition with developed control algorithm. In addition,
two hemodynamic energy indexes seemed to be different, EEP was shown to
maintain or decrease. Otherwise SHE was increased.
Conclusions: The developed algorithm can enhance the operation stability of
the applied pneumatic blood pump. Hemodynamic energy indexes have shown
different result.
449
Int J Artif Organs 2010 ; 33 ( 7): 450
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P18 (196)
CONSIDERATIONS FOR MINIMALLY INVASIVE CARDIAC ASSIST DEVICE
PLACEMENT
P.-L. Hsu1,2, D. Timms1,3, N. Gaddum3, R. McMahon2, T. Schmitz-Rode1,
U. Steinseifer1
1
Applied Medical Engineering, Helmholtz Institute, RWTH, Aachen, Germany;
2
Engineering Department, University of Cambridge, Cambridge, UK; 3Critical
Care Research Group, Prince Charles Hospital, Brisbane, Australia
Objectives: The development of minimally invasive and easily implantable
cardiovascular assist devices (CADs) has been stimulated in the last decade
to enable earlier usage in a wider heart failure patient population. In order to
realise the next generation of assist devices for targeted therapy, such as bridge
to recovery in combination with stem cell therapy, we investigated the effect of
various minimally invasive CAD placements to support the left and right heart
fucntion.
Methods: Atrium-to-artery (AA), ventricle-to-artery (VA), and artery-to-artery
(ArA) device placements were assessed. The resulting hemodynamics were
simulated both in a computer model (CAM) and a mock circulatory loop (MCL).
The rotary CAD was operated at different speeds to partially or fully support the
circulation for mild and severe heart failures. Pressure and flow waveforms were
analyzed along with pressure-volume loops to determine the stroke work (SW)
and ejection fraction (EF) for each case.
Results: Ventricular EF, SW and pump flows were found to be lower with AA as
compared to VA over all simulated heart failure conditions indicating superior
ventricular unloading but poor ventricular washout, particularly during severe
heart failure. Arterial placement of the device effectively reduced the ventricular
afterload; however, the potential for reduction of cerebral and coronary perfusion
was observed when the device was placed in the descending aorta.
Conclusions: While reduction in SW observed with AA cannulation would
provide an optimum environment for stem cell proliferation by allowing the
ventricle to rest, an accompanying decrease in EF may increase incidence of
thrombus. Arterial placement of the device also reduces ventricular afterload;
however, aortic positioning may reduce cerebral and coronary perfusion if
autoregulation mechanisms are not maintained.
P19 (94)
A MODEL OF PULMONARY CIRCULATION FOR CARDIOPULMONARY
INTERACTION ANALYSIS
T. Gólczewski, K. Zielin´ ski, K.J. Pałko, M. Darowski
Institute of Biocybernetics and Biomedical Engineering PAS, Warsaw, Poland
Objectives: Cardiopulmonary interactions are especially important in cases of
mechanical support of respiration because of unprofitable positive pressures
during the inspiration, possibility or necessity of asymmetrical support, etc. The
aim of the study was to create such a complex model of pulmonary circulation
that would enable us to analyze different kinds of the interactions and their
influence on the ventilation/perfusion ratio.
Methods: Each lung lobe was divided into 8-16 parts to simulate differences in
vascular resistance of vessels supplying these parts and the influence of gravity
on that resistance (hydrostatic pressures affecting the transmural pressure). The
resistance depended on the vessel volume being dependent on the transmural
pressure and nonlinear compliance. The resistance of small arteries depended
also on wall muscle tension. Parameters for each part of lungs was adjusted in
such a way that the sum of compliance and conductance of all parts gave the
values known from physiology. This model together with a virtual respiratory
system built up previously constituted the virtual cardio-pulmonary system (VC-
PS).
Results: The VC-PS enabled us to analyze purely mechanical interaction
(e.g. influence of the alveolar pressure on capillary blood flow and intrapleural
pressure on regional pulmonary flow) as well as interactions connected with gas
exchange during artificial ventilation. In particular (and in contrary to simpler
models): (a) the ventilation/perfusion ratio in a part of lungs depended on both
patient’s position (gravity influence) and localization of the part; (b) arterial blood
oxygenation fell insignificantly even if a greater part of lungs was not ventilated
because of hypoxic vasoconstriction.
Conclusions: The VC-PS seems to be a helpful tool to analyze cardiopulmonary
interactions. In particular, it may prevent from jumping to false conclusions when
the influence of ventilatory support mode on gas exchange is analyzed.
Acknowledgements: The work was financed by the grant NN518332235 from
the Ministry of Science and Higher Education, Poland.
450 © 2010 Wichtig Editore - ISSN 0391-3988
P20 (141)
BIVENTRICULAR HEART ASSISTANCE: PRELIMINARY TESTS ON THE
HYBRID (HYDRO-NUMERICAL) CIRCULATORY MODEL
M. Kozarski1, G. Ferrari2, K. Zielinski1, K. Gorczynska1, A. Di Molfetta2, K.J. Palko1,
L. Fresiello2, M. Darowski1
1
Institute of Biocybernetics and Biomedical Engineering PAS, Warsaw, Poland;
2
Institute of Clinical Physiology CNR Section of Rome, Rome, Italy
Objectives: The aim of the study is to show how hybrid (hydro-numerical)
circulatory model is effectively used to reproduce different clinical physiological
as well as pathological cases when parallel biventricular (LVAD and RVAD) heart
assistance is applied. That opens unique R&D and educational opportunities
to investigate and demonstrate influence of assistance procedures on
hemodynamic and energetic parameters of the circulation e.g. to show
situations when different timing or pressure are applied to artificial ventricles
during heart assistance.
Methods: The hybrid circulatory model is composed of two parts. The first
one, being a core of the model, constitutes a closed loop lumped parameter
numerical circulatory model with both ventricles described by the numerical time
variable elastance. The second one, hydraulic, minimized to barest essentials, is
connected to the numerical part by special hydro-numerical interfaces (based on
voltage controlled flow sources) playing a role of linear impedance converters.
These interfaces allow connecting hydraulic elements to any chosen point of
the numerical part of the model by creating numerical circuit bifurcations or, if
necessary, allow to replace some numerical model sections by their hydraulic
counterparts.
Results: Experimental results of the parallel assistance are presented in the form
of flow and pressure traces as well as working loops in P-V plane corresponding
to different biventricular situations, i.e. in physiology (left ventricular elastance
Emaxl = 3.3 mmHg/cm3, V0l = 5 cm3) and in pathology (Emaxl = 0.67-1.5 mmHg,
V0l = 15 cm3) when the assistance is applied.
Conclusions: The experimental results illustrate efficiency and time economy
of investigations carried out on the hybrid circulatory model as compared with
similar ones but run on the “classical” pure hydraulic circulatory models.
P21 (255)
CFD MODELLING OF A BI-DIRECTIONAL AXIAL FLOW LVAD
M.J.P. Swalen¹, C.S. König², A.I. Sayma³, A.W. Khir¹²
¹School of Engineering and Design, Brunel University, Middx., UK; ²Brunel
Institute for Bioengineering, Brunel University, Middx., UK; ³Thermo-Fluid
Mechanics Research Centre, University of Sussex, Brighton, UK
Amongst all long-term circulatory assist devices, axial flow pumps are
recognized for their small size and durability. A novel bidirectional axial flow
pump, envisaged to be placed at the aortic root, has been designed to offload
the left ventricle by circulating blood to the periphery during systole (forward)
and increasing the flow to the coronary arteries during diastole (backward). The
design process involved merging two standard NACA profiled blades that lead
to a symmetric profile that can generate pressure rise when rotated in either
direction. The aim of this study is to model the hydraulic performance of the
bidirectional blades and study the possible blood trauma.
3D computational fluid dynamics (CFD) studies were carried out to model the
bidirectional blades. The model was set so that the blade accelerates to a
maximum forward rotational speed of 8,000rpm, decelerates to a full stop within
30ms. Then changes the direction of rotation and accelerates to a maximum
backwards rotation speed of 2,400rpm. The CFD model was performed by
positioning the blades in a 25mm tube to simulate the physiological geometry.
Rotating in the forward direction, the blades generated 15mmHg and delivered
38cc. Rotating in the backward direction, the blades generated 1.1mmHg and
delivered 20cc. In the forward direction, maximum wall shear around the blades
was found to be ~ 150Pa lasting less than 30ms, in the backward direction this
was ~ 23 Pa lasting for 30ms.
The computational results show the designed blades delivered the required
pressure rise and flow rates during forward and backward rotation. The
calculated wall shear stresses are below the accepted limits of hemolysis
(200Pa). Analysis of streamlines did not show significant recirculation at the
exit of the pump, and experimental work is underway to validate the obtained
computational results.
Int J Artif Organs 2010 ; 33 ( 7): 451
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P22 (117)
A LUNGS PARTITION FOR SIMULATIONS OF CARDIOPULMONARY
INTERACTIONS IN A VIRTUAL PATIENT
K.J. Pałko1, D. Kołodziej2, T. Gólczewski1, K. Zielin´ ski1, M. Darowski1
1
PAS, Institute of Biocybernetics and Biomedical Engineering, Warsaw, Poland;
2
WUT, Department of Micromechanics and Photonics, Faculty of Mechatronics,
Warsaw, Poland
Objectives: Perfusion of a part of lungs depends on its distance from the
pulmonary trunk (differences in vascular resistance) and its distance from a
horizontal plane (differences in hydrostatic pressure). Lungs partition into parts
to assign the values of geometrical parameters characterizing their position and
size was the aim of the study.
Methods: The Autodesk Inventor Professional 2009 computer software (in
computer-aided design type) was used to elaborate a three-dimensional
geometrical lung model. Lung section outlines with the division into lobes
from an anatomical atlas and CT images were utilized. Each of lung lobes was
divided into 8 (the middle right lobe) or 16 (the others) parts with planes related
to four positions of the virtual patient (the planes were horizontal in one of these
patient’s positions: 1 or 3 planes corresponded to the vertical position; 1 plane
corresponded for each of the supine and left or right lateral positions).
Results: The part was identified with the vector [n,j,k,m], where: n=1..5 indicates
the “native” lobe; j, k, m describe part position in this lobe. The parts were
characterized with the following arrays: u0[n,j,k,m] – the relative volume of a part
in relation to the total lungs volume, long0[n,j,k,m] – the relative distance of the
mass centre of this part from the pulmonary trunk, and hydro0[n,j,k,m,pozycja]
– the relative distance of this mass centre from the dissection plane that is
horizontal for patient’s position indicated by the variable “pozycja”. The arrays
have been used in circulatory and respiratory models composing a virtual
cardio-respiratory system.
Conclusions: The presented work is a step in studies of the cardio-respiratory
system and its effect can be a useful tool for the science education and medical
research trainings.
Acknowledgements: The study was financed by the Polish Ministry of Science
and Higher Education as a grant no. NN518332235 (2008-2010).
Apheresis
P23 (246)
CERAMIC MEMBRANES FOR ENDOTOXIN REMOVAL
D. Freimark1, S. Kerker1, O. Hoppe1, N. Busse1, M. Ebrahimi1, G. Catapano2,
P. Czermak1,3
1
Institute of Biopharmaceutical Technology, University of Applied Sciences,
Giessen-Friedberg, Germany; 2Department of Chemical Engineering and
Materials, University of Calabria, Rende, Italy; 3Department of Chemical
Engineering, Kansas State University, Manhattan KS, USA
Objectives: Endotoxins are components of the bacterial cell wall and are found
in almost all fluids even in those which are poor of nutrients. This is a huge
problem for medical and pharmaceutical applications, because already small
amounts of endotoxin cause strong immune reactions. Endotoxin removal is
possible by e.g. filtration. Therefore normally polymer membranes are used.
The disadvantage of these membranes is their short life time. An alternative
are ceramic membranes because they are inert and long-lasting. This work
investigates ceramic membranes concerning their ability of endotoxin removal
from aqueous solutions e.g. dialysis water.
Materials and Methods: Several polymeric adsorber membranes and ceramic
membranes were investigated concerning their endotoxin removal ability.
Therefore membranes were loaded with aqueous endotoxin solutions (0-1000
EU/mL) and tested in cross-flow and dead-end modus. The permeat samples
were analyzed by the Limulus Amoebocyte lysate (LAL) test. The endotoxin
removal of a membrane was classified as sufficient at permeat endotoxin levels
under 0.25 EU/mL.
Results: Although adsorber membranes showed good endotoxin binding
capabilities the endotoxin removal was insufficient. Ceramic membranes
showed significant better endotoxin separation with endotoxin levels in the
permeat under 0.25 EU/mL even at endotoxin loadings of 1000 EU/mL in the
feed.
© 2010 Wichtig Editore - ISSN 0391-3988
P24 (206)
Image analysis of erythrocyte aggregation under rheo-
microscope
G. D’Avenio1, C. Daniele1, P. Caprari 2, A. Tarzia2, M.C. Martorana3, M. Grigioni1
1
Dept. of Technology and Health, Istituto Superiore di Sanità, Rome, Italy; 2Dept.
of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanità,
Rome, Italy; 3Dept. of Transfusional Medicine “Roma West”, S. Camillo Forlanini
Hospital, Rome, Italy
Objectives: The contribution of red blood cells (RBCs) to flow behavior of
blood is linked to cell deformability and aggregation. Diseases characterized
by alterations in RBCs are generally associated with hemorheological
abnormalities.
The aim of this work is to build a software tool capable of evaluating the
aggregation - disaggregation patterns of RBCs, either obtained from pathological
patients or subjected to prosthesis-related stress.
Methods: The study has been carried out using a Rheo-Microscope (Anton
Paar), constituted by a glass parallel-plate rheometer, and an optical microscope.
Whole blood was subjected at 37 °C to increasing shear rates [(between 1 and
250 s^(-1)] and simultaneously imaged with a CCD camera. Video sequences
of the flowing RBCs were subsequently analyzed. A custom software (written
in the Matlab environment) was used to determine, for each frame, the number
and size of the clusters of RBCs, by nonlinear filtering of the images (adaptive
thresholding, morphological operators). Thus, the time course of the mean
cluster area could be identified, for each shear rate value. The software has
been validated on synthetic RBC images.
Results: RBCs at rest or under low flow form rouleaux aggregates that have
a very structured network. The analysis of normal RBCs at increasing shear
rates have enabled to quantify the progressive destructuring of aggregates, in
terms of number of clusters created in unit of time, at increasing shear rate, until
complete disaggregation.
Conclusions: Image analysis was found to be capable of yielding useful
information on the erythrocyte aggregation and could be used to correlate the
hemorheological profile of healthy and pathological subjects with RBCs flow
behavior.
P25 (164)
“NUCLEOSORB” IN THE SLE-TREATMENT
D. Dus1, V. Kirkovskij1, D. Makarevich2
1
9th City Hospital, Minsk, Belarus; 2Belarussian State Medical University, Minsk,
Belarus
Progress of the modern treatment and diagnostic technologies in the last years
has led to increasing of the 5-years survival of the systemic lupus erythematosus
(SLE) patients up to 90%. On the other hand, severe chronic clinical SLE-course
with primary involvement of women, stable disability and increasing of the
prevalence result in great social significance of SLE and necessity of the further
search of new therapeutic approaches. So, development and using of the new
medical technologies possessing high selectivity of therapeutic influence on
immune-pathological process in SLE is of a great interest.
The purpose of this pilot study was to assess immunoadsorption (IA) on the
anti-DNA-sorbent “Nucleosorb” (Belarus) to remove auto-DNA-antibodies from
the whole blood of the SLE-patients with high activity.
IA using “Nucleosorb” has been done in 9 complicated SLE-patients which were
unresponsible to the routine treatment. All patients have been informed and
signed written agreement. Every patient has got 3 sessions of IA in one up to three
days. Auto-DNA-antibodies level was determined before and after every IA.
Analysis of laboratory data revealed decreasing of auto-DNA-antibodies level on
33% in average after every hemoperfusion and on 58% to the end of treatment.
Symptoms regression of the lupus nephritis on 18%, arthritis on 46%, Raynaud’s
syndrome on 28%, dermal manifestation on 16% were observed at the end of
treatment including IA. In addition, it is necessary to note that “Nucleosorb” was
done and successfully used for the whole blood purification.
So that, SLE treatment using IA on “Nucleosorb” led to the positive clinical
effects and was user-friendly for the staff because of its simplicity.
P26 (122)
COMBINED APPLICATION OF POLYMIXIN-CONTAINING AND
ANTIPROTEASIS SORBENTS IN COMPLEX TREATMENT OF PATIENT
WITH SEVERE SEPSIS
I. Rovdo, V. Kirkovsky, A. Starostin
Belarussian State Medical University, Minsk, Belarus
Objectives: To study the effectiveness of combined application of polymixin-
451
Int J Artif Organs 2010 ; 33 ( 7): 452
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
containing and antiproteasis sorbents in complex treatment of patient with
severe sepsis.
Methods: The present research was carried out on 15 patients (8 males, 7
females), average age 38±10 years. The diagnose of sepsis or severe sepsis was
based on SIRS and Gram-negative bacteremia presence. Patients conditions
were calculated by APACHE II and SOFA scores. The endotoxemia level was
estimated by turbo-dimetric method. All the patients were given the routine
therapy including: antibiotics, infusion, vasopressors, artificial lung ventilation.
The standard method of hemoperfusion was applied, polymixin-containing and
antiproteasis sorbents were placed in extracorporeal circuit in series.
Results: 48 hemoperfusion sessions were done, 3±1 in average per person.
The blood perfusion volume was 1-1.5 of total blood volume. In 12 patients we
recorded general condition improvement: hemodynamic stability, vasopressors
doses decreasing, the cancellation of artificial lung ventilation. It was correlated
with LPS –toxin level decreasing and improving parameters displaying SIRS and
MODS. 3 patients died because of organ dysfunction worsening.
Conclusions: We consider the combined application of the above mentioned
sorbents in complex treatment of patients with Gram-negative sepsis effective
and may be perspective, although further investigation is needed.
P27 (334)
SYNTHESIS OF MAGNETIC CELLULOSE MICROPARTICLES AS MATRIX
FOR MARKERS IN EXTRACORPOREAL BLOOD PURIFICATION
M. Ettenauer1, S. Fischer2, K. Thümmler2, V. Weber1, D. Falkenhagen1
1
Center for Biomedical Technology, Danube University Krems, Krems, Austria;
2
Institute of Plant and Wood Chemistry, University of Technology, Dresden,
Germany
Objectives: For special biomedical in vivo applications, a spherical morphology
with a defined particle size, the possibility of surface functionalization, as well
as biocompatibility are prerequisite. The Microspheres-Based Detoxification
System (MDS) utilizes combined membrane, separation and adsorption based
on spherical micro-particles (particle size 5-8 µm). These particles are separated
from the patient`s blood only by one membrane. To guarantee first fault safety
of the system in case of a membrane rupture, a particle detector based on
a magnetic trap combined with an optical detection system was developed.
Magnetic fluorescent particles are added to the adsorbent circuit and will
be detected in the venous blood line. The work presented here includes the
synthesis of magnetic spherical microparticles based on cellulose with a particle
size of less than 5 µm.
Methods: The synthesis of magnetic cellulose microparticles was performed in
two ways: (a) porous cellulose microparticles were synthesized by the acetate
process and magnetite was incorporated into the particles by co-precipitation of
FeII/FeIII in alkaline media or (b) commercially available magnetite nanoparticles
were incorporated into the polymer microparticles during the polymer synthesis
process. In both cases, various parameters, such as iron salt or magnetite
concentration, incubation time, dispersion parameters, as well as the influence
of protective colloids were investigated.
Results: The resulting magnetic particles were characterized by electron
microscopy, measurement of the particle size distribution as well as by
determination of their magnetic properties. Spherical magnetic cellulose
microspheres could be synthesized with a narrow particle size distribution
ranging from 1 to 10 µm, respectively.
Conclusions: In summary, we are establishing spherical magnetic cellulose
microparticles as matrix for the use of marker particles in the Microspheres-
Based Detoxification System.
P28 (225)
MEMBRANE PLASMAPHERESIS IN the TREATMENT OF ACUTE
OLIGOANURIA IN SEVERE LUPUS NEPHRITIS
L. Grcevska, M. Milovanceva-Popovska, V. Ristovska, A. Sikole
University Department of Nephrology, Skopje, R. Macedonia
Plasmapheresis appears to be a useful adjunct to conventional therapy in
the treatment of anti-GBM nephritis, severe dialysis-dependent forms of
pauci-immune RPGN and HUS-TTP. Controlled trials do not support a role for
plasmapheresis in immune complex-mediated RPGN, lupus nephritis (LN) and
acute allograft rejection. There are many reports about its use in SLE with central
nervous system affection, severe SLE vasculitis and resistant to treatment LN.
We treated with membrane plasmapheresis 5 adult female patients (aged 15-
33) with severe LN (class IV-3, class III-1, class VI-1), with acute oligoanuria and
dialysis-dependence. Plasmapheresis was an adjunct to i.v. methylprednisolone
and cyclophosphamide therapy. 4-6 plasma exchanges were performed, 2000-
2200 mL plasma was exchanged. Fresh frozen plasma and 20% albumin
452 © 2010 Wichtig Editore - ISSN 0391-3988
solution were used as substitution. The patient with class VI LN did not respond
to treatment. The patient with class III presented complete recovery of the renal
function, but relapse after 12 years, without rsponse to repeated treatment. All
patients with class IV LN presented complete recovery of renal function. One
is still in remission, the other two patients presented relapse of the disease
also after 12 months (early summer period) and again complete recovery after
repated treatment. These two patients during follow-up of 10 years did not
present acute oligoanuria again, but slow deterioration of the renal function was
observed. We can conclude that plasmapheresis may be used as an adjunct
to immunosuppression in severe LN, with acute oligoanuria and advanced
histological class at biopsy.
P29 (243)
PLASMAPHERESIS IN TREATMENT OF WEGENER’S GRANULOMATOSIS
V. Ristovska, L. Grcevska, M.M. Popovska, M. Popov, V. Nikolov, S. Dzikova
University Clinic of Nephrology, Skopje, R. Macedonia
Wegener’s granulomatosis is a systemic necrotizing vasculitis, which can be
with a fatal course, even in the cases when effective therapy is administered.
The disease is uncommon and the true incidence is difficult to determine.
Ten patients with Wegener’s granulomatosis, mean age 43.3+/-7.4 years,
8 of them males and 2 females, all of them ANCA (+), were treated with
plasmapheresis. We use plasmapheresis in patients with severe renal and
pulmonal involvement, because the patients with moderate form of the disease
achieved remission using treatment with corticosteroids and cyclophosphamide.
Respiratory tract involvement as multiple bilateral nodular cavitary infiltrates was
diagnosed by computerized tomography. Renal biopsy presented extracapilary
glomerulonephritis in 80% with crescents. Clinical feature at start of the follow-
up was as follows: all 10 patients had rapidly progressive glomerulonephritis,
diffuse extra-capillary crescents on renal biopsy, hypertension 150/90 and
170/100 mmHg, regulated with therapy, serum creatinine 600-1300 micromol/L,
all of them were treated with cortico-steroids, cyclophosphamide, but also with
plasmapheresis and dialysis. After 2 months 3/10 patients achieved remmission,
but the other 3/10 patients later started chronic hemodialysis treatment.
The other 4/10 patients with rapidly progressive glomerulonephritis with
serum creatinine 890-1890 micromol/L, were treated also with corticosteroids,
cyclophosphamide, plasmapheresis and dialysis, had poor prognosis and died
because of respiratory complications. In conclusion, we can say that despite the
used therapy, we have different outcome of the disease: in 3 cases we had complete
remission, in 5 cases we had 2 relapses, in 3 of them chronic hemodialysis treatment
was started, but in the other 4 cases it was not possible to achieve remission.
P30 (67)
Fluorescent testing of the main blood plasma proteins
functional state for the estimation of plasmapheresis
efficiency in the Rh- immunized pregnancy
V.V. Kirkovskiy1, A.K. Korolik1, E.V .Korolik2, E.A. Korolenko2, O.V. Kozljakova3
1
Belarussian State Medical University, Minsk, Belarus; 2B.I. Stepanov´s
Institute of Physics Belarussian National Academy of Science, Minsk, Belarus;
3
Belarussian Academy of the Post-Graduation Education, Belarus
It is well known that one of the treatment methods for Rh-immunized pregnancy
is plasmapheresis. But the questions of plasmapheresis efficiency in terms of
stabilization of the pathologic progress still remain open.
The main aim of the present work was to estimate plasmapheresis efficiency
in Rh-immunized pregnancy by using differently charged fluorescent dyes for
binding ability testing of the main blood plasma proteins: albumin, lipoproteins
and a-1-acid glycoprotein.
Samples of blood plasma from 19 Rh-immunized pregnant women taken
before and after plasmapheresis have been investigated. The total number of
the performed and estimated plasmapheresis sessions was 60. Using three
differently charged fluorescent dyes – anionic, cationic and neutral – functional
state of the main blood plasma proteins (albumin, α-1-acid glycoprotein and
lipoproteins, correspondingly) has been estimated in each sample.
It has been defined that including plasmapheresis in the treatment of the Rh-
immunized pregnant women lead to the little decreasing of cationic hydrophobic
metabolites transport according to results of α-1-acid glycoprotein binding ability.
Normalization of imbalance of uncharged hydrophobic metabolites distribution
between albumin and lipoproteins has been revealed after any plasmapheresis
session, but it had a short-time effect. We found differently directed changes of
albumin binding ability to the anionic hydrophobic metabolites: increasing of the
albumin molecules binding ability after plasmapheresis was a favorable sign for
these women, and decreasing of it had unfavorable clinical prognosis (preterm
delivery, high risk of hemolytic disease development in baby).
Int J Artif Organs 2010 ; 33 ( 7): 453
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P31 (311)
COMBINED EXTRACORPORAL METHODS IN MUSHROOM POISONING
TREATMENT
Z. Petronijevic 1, L.Tozija1, A. Asani1, I. Nikolov1, A. Sikole1, A Chibisev2
1
Clinic of Nephrology; 2Clinic of Toxicology and Urgent Medicine, Skopje,
R. Macedonia
Objectives: Mushroom poisoning is usually the result of ingestion of wild
mushrooms after misidentification of a toxic mushroom as an edible species.
It is generally acute and features of this poisoning include gastrointestinal
symptoms and in severe cases multi-organ failure, renal and hepatic failure.
Materials and Methods: Three patients with mushroom poisoning were
admitted with gastrointestinal symptoms after more than 24 hours of ingestion.
The first symptoms, vomiting, diarrhea, abdominal pain occurred after latency
period of few hours. Fluid and electrolyte replacement, gastric lavage,
oral activated charcoal and intensive combined extracorporal purification
treatment was performed in nephrology unit. Two patients were oliguric and
with increased levels of urea (s) 33.3mol/L and 25.8mmol/L, creatinine (s) 265
and 252 micromol/L. Liver enzymes showed marked increased, a-amylases
were elevated, hyperbilirubinemia and hypoproteinemia were present also. The
patient, whose renal function was not affected, was treated with hemoperfusion
and with plasmapferesis, which were performed at PRISMA with PF 2000 Set.
The second patient was treated with charcoal hemoprefusion and hemodialysis in
HD/HP circuits in three 8 h sessions and 3 times with additional plasmapheresis
(PF) using as filter Plasmaflux PSU 1S Fresenius. Two more hemodialys were
performed also. To the third patient the treatment was discontinued after
performing 3 HD/HP sessions and two PF, because of severe trombocitopenia
and hemorrhagic syndrome appeared.
Results: Two patients were discharged from the hospital with improved clinical
and biochemical findings. The patient with serum creatinine 175micromo/L
and preexisting chronic renal failure was not excluded and monitoring of renal
function was recommended. The third patient with severe trombocitopenia died
with cerebral complications.
Conclusions: There is no specific antidote for mushroom poisoning; intensive
combined treatment has life saving role and its fast processing may avoid
further kidney and other organ damage.
P32 (125)
HEMOSORPTION IN COMPLEX MANAGEMENT OF HEPATARGY
Sh.Z. Kasimov, B.M. Nurmukhamedov, D.S. Aripova
The Republican Specialized Center of Surgery named after Academician V.V.
Vahidov Tashkent, Uzbekistan
Objectives: To evaluate the applicability and efficacy of hemosorption in
management of patients with liver insufficiency.
Methods: We have studied the results of treatment with hemosorption in 17
patients with hepatic encephalopathy of II-III and IV stages according to A.F.
Blyuger et al. (1980) classification, who survived earlier hepatitis B or C. The
hemosorption was performed by carbonic sorbents of “SKN” series with the
volume of 400 mL through veno-venous extracorporeal circuit in hemoprocessor
“Unurol-5”. Perfusion rate was 40-60 ml/min, volume 1.5-2.0 liters.
Results: In the first group (11 patients), in the process of hemosorption 7
patients (63%) recovered from precomatose state, signs of intoxication being
significantly reduced. In 3 cases (27.3%) the repeated hemosorption cessions
were required (from 2 to 6), after which significant improvements were observed.
In one case (9.1%) the signs of hepatargy progressed and the patient died from
cardiovascular insufficiency. In the second group (6 patients) we observed
patients with hepatic insufficiency and encephalopathy of IV degree. The
traditional management slightly improved the hemodynamics and biochemical
parameters of blood. In 4 cases (66.7%) we only achieved some stabilization
and disappearance of Dollov’s symptom of eye bulb movement. But, regardless
of efforts, all of them died in 12-24 hour period. The autopsy discovered total
liver necrosis, pulmonary and cerebral edema. In other 2 cases, after the
hemosorption with the volume of 4500 mL through three columns, we observed
an improvement in patients condition, which allowed them to perform doctor’s
simple commands. In these patients the bilirubin content decreased on 47%,
prothrombin index after neutralization with heparin was 49%, paramecium
test increased on 55%. On 3-5 days the hands’ tremor and fetor hepaticus
disappeared, and appetite returned.
Conclusions: Received data proves the expediency of hemosorption in
complex management of hepatargy. Nevertheless, the means of increasing its
efficacy remain to be investigated.
© 2010 Wichtig Editore - ISSN 0391-3988
P33 (339)
ARTIFICIAL NUTRITION IN THERAPEUTIC APPROACH OF ACUTE
CAUSTIC POISONINGS
A. Chibishev, N. Simonovska-Veljanovska, Z. Pereska
1
Clinic of Toxicology, Medical Faculty, University “Ss Kiril and Metodij” Skopje,
R. Macedonia
Acute corrosive poisonings can cause serious chemical injuries of the upper
gastrointestinal tract; they are most frequently localized in the esophagus and
the stomach because poison remains there a long time. Treatment of the acute
corrosive intoxications include: neutralization of corrosive agents, antibiotics,
corticosteroids, anti-secretory therapy, nutritional support, collagen synthesis
inhibitors, esophageal dilation and stent placement, and surgery.
The damaged mucosa, submucosa and muscle layer regenerate with great
difficulty because of the surrounding inflammation, necrosis and secondary
complications. Tissue fibrosis, adhesions or circular stenosis appear, which
greatly disturb the normal functioning (impeded peristaltic, impeded passage).
All these complicate the entire general condition of the patient, including
inadequate normal food intake, loss of body weight, prostration, cachexia.
These patients are also into a severe general condition due to hypercatabolic
state and negative alkali balance. Therefore, early nutritional support is of
substantial importance in the treatment of these patients. Nutritional support
can be given by parenteral way in peripheral or central vein and by enteral
way through specially designed tubes inserted in the stomach or intestines,
prepyloric or postpyloric.
The type of artificial nutritional support will depend on the grade of esophageal
or gastric damage determined by endoscopy.
Tissue Engineering 1
P34 (314)
IS MILD HYPOTHERMIA (34°C) COOL ENOUGH TO PROTECT
CARDIOMYOCYTES FROM ISCHEMIC INJURY?
P Soltani1, F Berger1,2, C Drescher1, S Wollersheim1, K Schmitt1
1
Department for Congenital Heart Diseases / Pediatric Cardiology, Deutsches
Herzzentrum, Berlin; 2Department of Pediatric Cardiology, Charité –
Universitätsmedizin, Berlin, Germany
Objectives: Myocardial ischemia may occur during cardiac arrest and/or
previous to artificial device supply of cardiac insufficient patients. Therapeutic
hypothermia has been established as a powerful instrument to protect from
ischemic injury. In clinical practice mild hypothermia has been proven to be
easier to induce and maintain than hypothermia below 32°C. Furthermore fewer
side effects have been observed under mild hypothermia. The aim of our study
was to probe whether mild hypothermia is a sufficient therapeutic method to
reduce ischemic injury and increase cellular function. Due to the intention to
illuminate the underlying cellular mechanisms during mild hypothermia and to
exclude other factors of influence we decided to perform a study in a cell culture
of cardiomyocytes (H9c2) at first.
Methods: Cardiomyocytes (H9c2) were exposed to 30mM CoCl2 for an hour to
simulate a transient ischemia. This ischemic event is followed by a hypothermic
phase (34°C) for up to 48h. Cell viability (trypan blue), mitochondrial enzyme
activity (MTT-test), production of reactive oxygen species (ROS) and ATP-level
were analyzed at different stages.
Results: Mild hypothermia is powerful enough to protect cardiac cells after an
ischemic injury as demonstrated in a significant increase of cell viability and
less cell death. Effects of reperfusion injury were effectively alleviated by mild
hypothermia as observed in a decrease of ROS production. Unexpectedly
there was a significant increase in mitochondrial enzyme activity during mild
hypothermia. Hypothermic cardiomyocytes demonstrated a significant higher
cell activity after the ischemic injury in comparison to cardiomyocytes kept
under normothermia after the ischemic injury.
Conclusions: Lowering temperature to 34°C is powerful enough to induce
protective mechanisms of hypothermia after an ischemic injury in a cell culture
model.
453
Int J Artif Organs 2010 ; 33 ( 7): 454
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P35 (282)
CARDIOPLEGIA REDUCES HYPOTHERMIA-INDUCED
CARDIOPROTECTIVE MECHANISMS
C. Drescher1, S. Wollersheim1, P. Soltani1, F. Berger1,2, K.R.L. Schmitt1
1
Department of Congenital Heart Disease / Pediatric Cardiology, Deutsches
Herzzentrum Berlin, Germany; 2Department of Pediatric Cardiology, Charité -
Universitätsmedizin Berlin, Germany
Objectives: Hypothermia and cardioplegia, or both are two most frequently
applied methods in practice to protect heart against ischemic injury. The decision
to use either of these current techniques of myocardial protection is intimately
linked to the understanding of the underlying basic mechanisms. Therefore
the objective of the present study was to assess possible underlying cellular
mechanisms of hypothermia- and or cardioplegia-induced cardioprotection.
We investigated heme oxygenase 1 (HO-1) expression after simulated
cardiopulmonary bypass (CPB) in a H9c2 cardiomyocyte culture in vitro model.
Methods: For simulated CPB we cooled cardiomyocytes to 20°C, maintained 20
min at 20°C during which short-term oxidative damage was inflicted with 2 mM
H2O2; simultaneously cells were exposed to cardioplegic solution, afterwards
rewarming to 37°C. Later on we analyzed intracellular ROS production,
expression of HO-1 via western blot technique, intracellular ATP-level and cell
morphology by phase contrast microscopy.
Results: Hypothermia protects mitochondria from oxidative stress demonstrated
in a tolerance against high intracellular ROS levels and a better ATP level
recovery. Six hours after H2O2 damage cooled and rewarmed cardiomyocytes
showed a higher expression of HO-1, persistant up to 24 hours later. Interestingly,
additional exposure to cardioplegic solution during H2O2 damage reduced this
effect significantly. Moreover intracellular ATP level was not restored effectively
after cardioplegia.
Conclusions: In this cell culture study we could show that cardioplegic solution
reduces hypothermia-induced protection mechanisms (HO-1) of cardiomyocytes
during simulated CPB.
P36 (59)
EFFECT OF PREDNISOLONE ON ELECTROPHYSIOLOGICAL
CHARACTERISTICS OF ISOLATED DISTAL COLON WALL
T. Grzelak, K. Wojciechowska, K. Czyzewska
Department of Chemistry and Clinical Biochemistry, Poznan University of
Medical Sciences, Poznan, Poland
Objectives: Prednisolone and another glucocorticoid are used for the treatment
of inflammatory bowel diseases. Although corticosteroids are potent inhibitors
of different processes during colitis, the mechanism of their influence on
electrophysiological properties is little known. The objective of the study was to
examine the influence of prednisolone on the electrical parameters of colon.
Methods: Experiments consisted in measurements of the spontaneous potential
difference (PD) and resistance (RTM) of isolated rabbit distal colon wall placed in
Ussing apparatus. The tissue separates two chambers filled up with isoosmotic,
complex electrolyte solution (Hanks fluid with 100 mg/Dl glucose) with constant
Ph=7.4 and temperature 37 Celsius degree. Electrical parameters of colon
segments were monitored with a dual voltage/current clamp in the control stage
(1-40 min) and after prednisolone (1 mg/Dl or 2 mg/Dl, 41-80 min) introduction
at the luminal side of the bowel in the two separate series. Measurements were
done at selected times (every minute in first 10 minutes and every 5 minutes in
remaining time, respectively).
Results: The control spontaneous potential difference of colon wall was similar
in the case of both series and amounts at mean -4.317±3.677 Mv (±SD).
Prednisolone reversibly decreases PD by at mean 16% (p=0.05) after 2 and
3 minutes in the concentration of 2 mg/Dl, but not in the case of 1 mg/Dl. The
control resistance of tissue accounts at mean 159.5±53.4 ohm x cm x cm.
Prednisolone induced a reduction of RTM by at mean 13% (p<0.05) in the case
of 1 mg/Dl concentration and by at mean 22% (p<0.02) for 2 mg/Dl within 20
minutes, which continued for the entire experiment.
Conclusions: We concluded that, prednisolone concentration-related modifies
ion transfer, decreases resistance and increases the transepithelial permeability
of distal colon. Observed results may be clinically important especially in
patients with inflammatory bowel diseases.
454 © 2010 Wichtig Editore - ISSN 0391-3988
P37 (153)
ESTERs OF HYALURONIC AND BUTYRIC ACID PROTECT RENAL CELLS
IN AN IN VITRO MODEL OF ISCHEMIC INJURY
F. Bianchi1, G. La Manna2, E. Olivi1, F. Bonavita1, C. Cavallini1, S. Cantoni1,
C. Ventura1, S. Stefoni2
1
Lab of Mol. Biology and Stem Cell Engeneering; 2Nephrology, Dialysis and
Renal Transplant Unit S. Orsola Univ. Hosp., Bologna, Italy
Objectives: We have recently demonstrated in a rat model of acute kidney injury
(AKI), the improvement of renal function by the use of human mesenchymal
stem cells. This effect is remarkably higher when the cells are pretreated with
esters of Hyaluronic and Butyric acids (HB). Persistent tissue hypoxia following
AKI induces kidney cells to die and contributes to the development of chronic
renal failure. Here we indagate if the use of HB could protect mesangial cells
(MC) from death in an in vitro model of ischemic injury.
Methods: MC from 2-day-old rats were cultured in RPMI 1640 with 10% FBS.
MC were pretreated with HB (1g/L) or grown in culture media for 24h, before
adding H2O2 50µM to simulate in vitro ischemia/reperfusion (I/R) damage. Cell
death was measured by quantification of lactate dehydrogenase (LDH) release
into the media, as marker of necrosis, or analysis of caspase-3 (CASP3) activity
by fluorometric assay and phosphorylation of P38 by Western Blot, to evaluate
apoptosis.
Results: H2O2 treatment resulted in an induction of cell death that is strongly
inhibited by HB. This effect peaked at 16h, when the mortality rate of MC
pretreated with the ester is 38% lower than non pretreated cells. The high
release of LDH and the low activity of CASP3 in H2O2 treated cells demonstrated
necrosis. At 16h CASP3 activity is higher in HB pretreated cells, indicating that
in this case cells die for apoptosis, as confirmed by P38 phosphorylation. Thus,
HB prevented or delayed the process of necrosis within the first 16h, preventing
the inflammation related to this process.
Conclusions: We demonstrated that HB protect MC from injuries induced by
oxidative stress, like those observed in I/R. As the timing for cell expansion will
involve a delay in stem cell transplantation with respect to the acute phase of
AKI, this effect would be important in order to use HB as first aid to rescue a
damaged kidney, that may be followed by transplantation of stem cells.
P38 (316)
Modeling cellular biophysical response of 3T3 cells during
freezing
M. Akhoondi, B. Alasmacher, W. Wolkers
Institute for Multiphase Processes, Leibniz University of Hannover, Germany
Objectives: Cells experience dramatic biophysical changes during cryo-
preservation processing including dehydration and/or intracellular ice formation,
which both lead to cellular injury.The aim of this study was to improve
cryopreservation of mammalian cells based on water transport modeling which
reveals the cellular volumetric behavior during cryopreservation.
Methods: We have investigated membrane phase behavior of 3T3 cells during
freezing using Fourier transform infrared spectroscopy (FTIR). This technique
allows monitoring cells during freezing in real time. Changes in the membrane
conformational disorder during freezing were used as a measure to determine
cell volumetric shrinkage. Ice nucleation was induced during cooling at different
temperatures. We have developed a Graphical user interface in MATLAB for
spectra analysis and data processing. To study the effect of ice nucleation on
membranes, characteristic lipid and water bands were analyzed in the acquired
spectra. The band position of the lipid symmetric CH2 sterching vibration at
2850cm-1 was used as measure for the membrane phase state during cooling.
In order to determine exactly the ice nucleation temperature, the water-to-ice
transition was followed by monitoring the H2O – libration and –bending band
between 2683-1965 cm-1. The obtained data from the water band and the lipid
band were used to study the effect of ice formation on the membrane phase
state. Finally, Obtained lipids analyzed data were fitted to an Arrhenius plot in
order to predict activation energy of membrane dehydration during freezing.
Results: The result shows that membranes undergo a fluid-to-gel phase
transition at the onset of ice nucleation. Analysing membrane dehydration
during freezing at different nucleation temperatures shows that freezing-
induced membrane phase changes depend on the ice nucleation temperature.
The dehydrating effect of the nucleation temperature on the membrane phase
state displays Arrhenius behavior.
Conclusions: We have shown the feasibility of FTIR spectroscopy as a powerful
technique to study the biophysical response of cells during freezing. Ice formation
during cooling causes a lytropic phase transition of cellular membrane.
Int J Artif Organs 2010 ; 33 ( 7): 455
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P39 (130)
Fabrication and Characterization of high interconnected
Hybrid Gelatin/Chitosan Scaffolds for Tissue Engineering
M. Pezeshki, H. Mizradeh, M. Zandi, M. Daliri, S. Irani
Polymeric Biomaterials, Iran Polymer and Petrochemical Institute, Tehran, Iran
Objectives: The field of tissue engineering has grown in response to the many
medical needs for tissue replacement and offers a new promising approach
to tissue and organ repair. In one approach, cells are seeded onto a three
dimensional (3D) biodegradable scaffold which acts as an artificial extra cellular
matrix (ECM), followed by in vivo implantation.
Materials and Methods: Mono layer porous chitosan/gelatin hybrid scaffolds
with high interconnectivity of pores were designed as a scaffold of dermis
tissue engineering via the salt-leaching technique by using the sodium chloride
microparticles as porogen.
Results: The salt-leached chitosan/gelatin scaffolds were easily formed into
desired shapes with a uniformly distributed pore structure with an average pore
size of around 200 µm. Samples with two different ratios of chitosan/gelatin to
salt crystals were prepared and characterized and some properties, such as
microstructure, porosity, phosphate buffered saline (PBS) solution adsorption
and biocompatibility were studied. The samples were highly porous and
interconnected with uniform pore morphology. Reduction of salt to chitosan/
gelatin ratio from 10 to 5 causes reduction in porosity and increasing in pore size.
The PBS solution absorption and porosity of samples increase with increasing
of salt ratio. The optical microscopic image of primary cell culture tests reveal
that after 48 h of in vitro culturing, the fibroblasts in salt-leached scaffolds were
mainly attached on the surface of the pores into the scaffolds.
Conclusion: The structural, mechanical and physical properties, PBS
absorption, and biocompatibility of the hybrid gelatin/chitosan scaffolds were
systematically investigated and the results show the gelatin/chitosan hybrid
scaffold is a potential scaffold for skin tissue engineering.
P40 (61)
CONTROLLING CELL ADHESION WITH LAYER-BY-LAYER TECHNIQUE
AND NANOSPHERE LITHOGRAPHY
M. Niepel, D. Peschel, H.S. Leipner, B. Fuhrmann, T. Groth
Martin Luther University, Institute of Pharmacy, Biomedical Materials Group
Halle-Wittenberg, Halle, Germany
Surface features like chemical composition, wettability, charge, viscoelasticity,
and topology are of great importance as any biomaterial interacts with the
biological environment through its surface. Different surface modification
techniques have been developed to improve material-cell-interaction. We have
applied the layer-by-layer (LbL) technique and the nanosphere lithography (NSL)
to control cellular behavior on biomaterial surfaces.
A multilayer system of poly-(ethylene imine) (PEI) and heparin (HEP) was
successfully designed. The Ph value of HEP solution during multilayer formation
was varied to obtain distinct surface features. Quartz crystal microbalance
with dissipation (QCM-D), atomic force microscopy (AFM) and confocal laser
scanning microscopy (CLSM) were used to investigate multilayer properties
and their influence on human fibroblast adhesion. Further, we have designed
nanostructured surfaces with NSL, which were investigated with scanning
electron microscopy (SEM) as well as AFM studies. Activation of the gold
nanostructures and passivation of the substrate surface were investigated using
fluorescently labelled proteins and CLSM.
QCM-D studies showed a mass increase after polyelectrolyte adsorption and
a change in growth regimes after Ph variation. On terminal layers composed of
HEP the formation of focal adhesions and actin cytoskeleton were absent at Ph
5.0 while at Ph 9.0 these structures were well developed. All multilayers were
rather smooth as AFM studies revealed only structures within the nanometer
range. Gold dots of different size and shape were designed with varying
polystyrene nanosphere sizes for template fabrication.
Multilayers of PEI and HEP with varying surface features were appropriate to
control fibroblast adhesion. Further experiments will combine NSL with LbL
to explore its potential to control cellular activity like adhesion, growth and
differentiation by variation of distance and size of gold dots and composition of
multilayers formed on the gold dots.
© 2010 Wichtig Editore - ISSN 0391-3988
P41 (129)
DIET CONTRoL EXPANDING CAPSULE USING TRANSCUTANEOUS
ENERGY TRANSMISSION
T. Yambe, Y. Shiraishi, H. Miura, Y. Saiki, K. Fukushima, M. Yoshizawa
Tohoku University, Sendai, Japan
In every country all over the world, the treatment of obesity is one of the most
important problems, when we consider the medical economy of all governments.
95% of obesity patients were reported to fail to control their weight only by
diet treatment. The surgical operation is considered is considered for obese
subjects with difficulty in controlling their weight. Of course, there is a possibility
of complication in surgical operation. The Tohoku University started developing
the Expansion capsule with transcutaneous energy transmission system (TETS)
having the same effect as the surgical operation for diet control. The capsule
in the stomach will expand mechanically by energy transmission from outsides
of the body after drinking, when the obesity patients will feel hungry. Small
linear drive with folding umbrella type actuator enabled us the expansion of
the diet capsules. Shame memory alloy (SMA) actuator was also the candidate.
Folding umbrella type and hanging scroll type SMA actuator were designed and
compared in the concept. Satisfactory characteristic of the energy transmission
was obtained by the trial model of TETS during animal experiments using
healthy adult goats with same weight of average Japanese people. Animal
experiments with healthy adult goats enabled us to evaluate the inner stomach
pressure time series changes. Double blind test of the expending capsule is
now under planning. If the expanding capsule diet control system is embodied,
it will become the gospel of the obese subjects.
P42 (193)
PERMANENT CENTRAL VENOUS CATHETER WITH A LOCK BALLOON
S. Weber, L. Goubergrits, U. Kertzscher, K. Affeld
Biofluid Mechanics Lab, Charite – Universitaetsmedizin Berlin, Berlin, Germany
Objectives: Permanent vascular access is essential for hemodialysis,
parenteral nutrition and drug administration. Mostly a central venous catheter
(CVC) is used. However, this use poses a problem: infection. The cause is the
intraluminal space, which acts as a bioreactor during the time when the CVC
is idle. To prevent this, a bactericidal liquid, called a lock solution, is injected
into the intraluminal space. For fluidmechanical reasons, it is not possible to
completely fill the intraluminal space without injecting the lock solution into the
bloodstream. The proposed lock balloon fills the intraluminal space and makes
a lock solution redundant.
Methods: Simulation of lock solution inflow: The inflow of a lock solution into
a double lumen catheter was investigated using computational fluid dynamics
(CFD). Conceptional work: The lock balloon was realized by replacing the axial
filling with a radial filling and by using a membrane interface instead of a fluid.
Results: The CFD simulation showed the protrusion of a central core of the
lock solution during infusion. The wall remained free of the lock solution. The
filling of the lumen was achieved with the lock balloon, an elongated, enclosed
balloon remaining permanently inside the CVC. During infusion the lock balloon
is collapsed and the lumen is free for the passage of the infused liquid. After
infusion the lock balloon is inflated again and completely fills the intraluminal
catheter space. A bi-stable piston secures the simple collapse and filling action
of the lock balloon. This was realized for a 10 French single lumen catheter. The
lock balloon was fabricated of polyurethane with a thickness of 0.1 mm. Filling
and emptying was done with a fluid. The collapsed lock balloon only slightly
reduced the infusion flow.
Conclusions: The concept appears valid and further investigations will deal
with miniaturization of the lock balloon and animal experiments. The animal
experiments are designed to model the routine of CVC use. Conventional CVCs
will be compared to lock balloon CVCs. Blood cultures after catheter use will
be used as a control.
455
Int J Artif Organs 2010 ; 33 ( 7): 456
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
Tissue engineering 2
P43 (290)
AN INNOVATIVE TELEMANIPULATOR FOR SAFE TRANSCATHETER
ABLATION
E. Marcelli1, L. Cercenelli1, F. Di Monte2, D. Caponi2, F. Gaita2, G. Plicchi1
1
Clinical Radiology Dept., Biomedical Technology Unit, University of Bologna,
Bologna, Italy; 2Division of Cardiology, Cardinal Massaia Hospital, University of
Turin, Asti, Italy
Objectives: Recently, two robotic catheter navigation systems (the Niobe® -
Stereotaxis, Inc., St. Louis, MO and the Sensei® - Hansen Medical, Mountain
View, CA) have been introduced into clinical practice, both enabling remote
control of ablation (AB) catheters. However, the issue of providing a safe and
effective way to perform remotely what commonly electrophysiologists carry
out manually remains unsolved. We evaluated the safety and efficacy of a novel
Remote Catheter Manipulator (RCM) which allows remote manipulation of
standard AB catheters, thus preserving the safe buckling property of a standard
catheter and being equipped with a force feedback mechanism which alerts the
operator when an excessive force is exerted by the RCM.
Methods: In 4 sheep, a standard 7.5 Fr AB catheter was inserted via the right
femoral vein using a standard long sheath introducer and it was manually
advanced to the right atrium (RA) under fluoroscopy visualization. The AB
catheter handle was then placed on the RCM to be remotely manoeuvred. In all
animals, the RCM was used in conjunction with fluoroscopy and the 3D mapping
system CARTO™ (Biosense Webster Inc., Diamond Bar, CA) to perform remotely
RA mapping and radiofrequency (RF) ablation of RA endocardial target sites.
Results: For all experiments remote RA mapping and RF ablation were achieved
safely, i.e. without causing any injury for cardiac tissue or inducing any alteration
in cardiac rhythm. Using the RCM, the operator successfully positioned the AB
catheter to all target ablation sites. Effective RF lesions performed by the RCM
were observed by visual inspection of the excised heart.
Conclusions: The novel RCM appears to be safe and effective to perform
remotely cardiac mapping and transcatheter ablation. The force feedback
mechanism proved to be a feasible tool to automatically prevent cardiac
tamponade. Further experimental and clinical studies are needed to confirm
these preliminary results.
P44 (343)
Teflon Piston surgery in conductive hearing loss
I. Filipche
University ENT Clinic, Skopje, R. Macedonia
Objectives: To evaluate the results of primary stapes surgery for otosclerosis
with up to 25 years of follow-up in a conductive series of 1000 patients operated
on by the same surgeon with the same technique stapedotomy and to provide
online access to the complete data of this study for the reviewers. Study design:
Prospective clinical study using a new computerized otologic database.
Patients and Methods: 925 patients who underwent 1.0 stapedetomies for
otosclerotic stapes fixation were enrolled in this study from 1980 to 2008.
Separate analyses were made for two unique pathologies (132 cases of
obliterative otosclerosis and 23 cases of simultaneous malleus ankylosis)
diagnosed during surgery and for patients in two age brackets [(< or = 15yr
(28 patients) and >or = 65yr (302 patients)]. Intervention: Stapedotomy and
reconstruction with Teflon piston or a total prosthesis. Main outcome measures:
Preoperative and postoperative audiometric evaluation using conventional
audiometry. Air-bone-gap, bone-conduction thresholds, and air-conduction
thresholds were all assessed. Postoperative audiometry was performed at 3, 6,
9, 12 and 24 months and then annually for 28 years.
Results: Overall the postoperative ABG was closed to 10db in 91.2% of cases.
The mean four–frequency postoperative ABG was 1.2db compared with 27.2db
preoperatively. The mean four-frequency bone-conduction thresholds were
unchanged postoperatively. A significant postoperative sensorineural hearing
loss (SNHL; >15db) was seen in 0.7% of cases in this series. Postoperative
ABG was achived within 10db in 92% of cases of oblitarive otoscvlerosis and
70,2 of cases of simultaneous malleus ankylosis. A significant postoperative
SNHL (>15db) was seen in 5.2% of cases of oblirative otosclerosis and was not
observed in any cases of simultaneous malleus ankylosis. Postoperative ABG
was, achived within 10db in 98.1% of cases in the pediatric series and in 93.5%
of cases in the senior series. A significant postop. SNHL >15db was seen in
1.0% of cases in the senior group but was not observed in children.
Conclusions: Our results confirm that stapedotomy for otosclerotic stapes
fixation is a safe and successful treatment for long-term hearing improvement.
456 © 2010 Wichtig Editore - ISSN 0391-3988
P45 (344)
AUDIOLOGICAL INCLUSION CRITERIA FOR COCHLEAR IMPLANTATION
M. Davcheva Chakar, V. Ivanovska, I. Filipce
University ENT Clinic, Skopje, R. Macedonia
Objectives: Hearing loss is one of the most common sensory impairments.
Approximately 1-3 out of 1000 newborns has hearing impairment. Cochlear
implantation is a life-changing event in many patients with hearing losses that
are not effectively managed with well-fitted hearing aids. With the experience
most implant users are able to understand spoken speech in the everyday
world. Cochlear implant is a surgically placed device that provides sound
perception through direct electrical stimulation of the hearing nerve bypassing
the inner ear. The aim of this study was to determine the candidates for cochlear
implantation.
Materials and Methods: Candidacy for cochlear implantation is determined by
a team of specialists which includes an otologist, an audiologist, a pediatrician,
a radiologist, a speech therapist, an educational specialist, and a social worker.
Audiologic evaluation: The hearing status in young children was evaluated by
following two methods: 1. behavioral assessment and 2. objective audiological
tests: (OAEs, BAEP, acoustic immittance tests, tympanogram and acoustic
reflex) CT and MRI. In older children, additional subjective audiological tests
were used: play audiometry, PTA, free-field aided PTA, free-field aided speech
audiometry. During the period of one year, 2007-08 at the ENT Clinic, Dept of
Audiology 540 hearing-impaired children were registered.
Results: The results showed 475 cases with conductive type of hearing loss
and 65 with sensorineural type of hearing impairment. 15 children in the second
group were deaf and another 10 had severe to profound hearing loss. The
results obtained from 15 children with severe to profound deafness had absent
otoacoustic emissions and normal results obtained with ABR. All previously
fitted children did not benefit from appropriate hearing aids.
Conclusions: Our candidacy issues for children are as follows: The child
with a bilateral (both ears), profound sensorineural hearing loss should be
considered for cochlear implants, failing to progress in speech, language, and
listening development with traditional hearing aids and absence of medical
contraindications should be considered as a candidate.
P46 (227)
Effective Parameters on Dexamethasone Release Profile
from silicone coated Cochlear Implant
F. Farahmand1, M. Imani1, H. Mirzadeh1, C. Jolly2
1
Iran Polymer and Petrochemical Inst., Tehran, Iran; 2Electrode Research
Section, MED-EL Company, Innsbruck, Austria
Objectives: A cochlear implant (CI) is a surgically implanted hearing aid device
which compensate for damaged or non-working parts of the inner ear. Post-
surgical infections and inflammations are the major risks associated with cochlear
implantation surgery. Drug elution from cochlear implant coating is a novel way
firstly proposed by the authors for drug delivery to the inner ear without need to
any extra equipment. A drug eluting electrode will be reported here and effects
of influential parameters on the drug release profile were investigated.
Materials and Methods: Two parts, silicone elastomer, were purchased from
Nusil. Micronized dexamethasone (DEX), and normal saline were purchased
from Aventis and Daroupakhsh Co., respectively. DEX (0.25 to 2% w/w of the
final cured compound) was mixed with part A of the silicone rubber. Part B
was added in different ratios i.e. 1:10, 0.75:10 & 0.5:10 to part A. Compounds
were injected into a mold to be cured. Release tests were performed for three
batches for each composition. DEX concentration was analyzed by HPLC.
Results: Cumulative percentage of DEX released from devices in normal saline
solution followed the order of 0.25%>0.35%>0.5%>1%>2% w/w. Drug release
pattern from a network can be controlled by varying its crosslink density hence,
crosslink densities were changed by changing the ratio of Part B to Part A.
Cumulative percentage of drug released (for 0.25 & 0.5% loaded devices) for
different crosslinking ratios was investigated. The drug released cumulative
percentage was increased by decreasing in crosslink density which also affected
the total effective release period and burst effect, simultaneously. However,
changing this ratio from 0.5 to 0.75 does not have a considerable effect on
the release profile. Effect of the device surface area on the release profile was
investigated for 1 & 2 cm length of devices. Upon duplicating the surface area of
the electrodes, the cumulative amount of drug released on each time point was
increased two folds. Increased loading affected the release profile in a different
manner where it caused a square-root-of-loading increase in the cumulative
amount released, which indicates full adherence of the designed system to
monolithic matrix systems as predicted by Higuchi model.
Conclusions: The effects of three effective parameters, i.e. drug loading
Int J Artif Organs 2010 ; 33 ( 7): 457
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
percentage, crosslink density and surface area on the release profile of drug
eluting cochlear implant coatings were investigated to provide optimized values
for parameters to achieve a certain dose per day profile. The results indicated
that the device is a monolithic device well fitted by Higuchi model.
P47 (342)
ENDOPROSTHETIC JOINT implANTS AND QUALITY OF POSTOPERATIVE
LIFE
M. Samardziski, G. Zafiroski, J. Malinovska
Clinic for Orthopedic Surgery, Skopje, R. Macedonia
In the period 2007-2009, at the Clinic for Orthopedic Surgery in Skopje, 47
patients with endoprostheses were evaluated for the quality of postoperative
life. Due to degenerative joint disease 27 patients had hip and 3 knee
endoprosthetic implants. The rest 15 patients had hip implants after geriatric
fracture of the proximal femur and the last 2 had special knee endoprostheses
after primary bone tumors. The patient’s results were analyzed with International
Limb Salvage Society score (ILSS). Best results were evaluated in patients with
degenerative joint disease (mean 89% function, according to ILSS), then were
patients with geriatric fractures of the femur (mean 67% function), and worst
results were evaluated in bone tumor patients (63%). Most of the patients (39/47
or 83%) were satisfied with postoperative overall function and will repeat the
procedure if needed. In spite of statistical difference between the function of the
operated joints in patients with degenerative diseases and geriatric fractures
and tumors, the differences in postoperative emotional acceptance was not
statistically confirmed.
P48 (303)
MASSIVE ENDOPROSTHESES FOR BONE TUMORS
G. Zafiroski, S. Mladenovski, D. Savev, M. Spirkoski, M. Samardziski, A. Dimova
Special Hospital for Surgical Diseases “Filip Vtori” Skopje, R. Macedonia
Objectives: One of the most challenging problems in orthopaedic oncology is
reconstruction following resection of bone tumors. Indications for reconstruction
after resection of bone tumors have broadened with adjuvant chemotherapy.
Materials and Methods: Among more than 30000 artificial joints implanted
in the orthopaedic hospitals in the Republic of Macedonia since 1968, we
analyzed 46 patients with special designed implants. From January 2000 to
January 2010, 46 patients with bone tumors and bone metastases were treated
at our hospitals. Histology included: 16 chondrosarcoma, 8 osteosarcoma, 2
fibrosarcoma, 1 Ewing’s sarcoma, 4 giant cell tumors and 15 bone metastases.
There were 24 females and 22 males ranging in age from 12-72 years (mean
51 years). Applications of massive endoprostheses were indicated in G0-
aggressive bone tumors, low-grade malignant or G1, high-grade malignant
or G2 and in bone metastases or G3. A custom-made Link, Lima and Kotz
modular artificial joints were used. The size of endoprostheses were from 12-24
ccm. In 2 patients we used total femur, endoprotheses, the proximal femur in
22, distal femur in 12, proximal tibia in 2 and in 8 patients proximal humerus
endoprostheses.
Results: The results varied depending on whether the procedure was performed
for palliation or for care. Survival after resection and reconstruction with artificial
joints is not significantly altered compared with amputation. The functional
results in artificial joints were as follow: in 5 (10.8%) may be expressed as
excellent, in 33 (71.9%) as good, in 5 (10.8%) as fair and in 3 (6.5%) as poor. In
8 (17.3%) we had complications.
Discussion: More than 70% of newly diagnosed patients with malignant
bone tumors are expected to be cured as a result of surgery and effective
chemotherapy. Chemotherapy has facilitated limb salvage operation in more
than 80% of patients.
Conclusions: The use of artificial joints can offer a realistic alternative
to disarticulation for bone tumors. In selected cases, the custom made
endoprotheses offer good functional results.
P49 (70)
DENTAL PULP MESENCHYMAL STEM CELLS (DPMSC) LASER ASSISTED
DIFfERENTIATION PRIOR TO BONE ENGINEERING
V. Marchiori-Silva, F.H. da Silva
USP-IPEN
Objectives: The objective of this study is to analyze the possible relation
between 830nm GaAlAr laser radiation and the gene expression of the genes
linked to differentiation of dental pulp mesenchymal stem cells (DPMSC).
Methods: The DPMSC were obtained from human dental pulp of third molars
extracted from patients aged from 21 to 45 years old according to the Ethics
© 2010 Wichtig Editore - ISSN 0391-3988
Committee of University of Sao Paulo. Cells were separated from the pulp tissue
by digestion with 3mg/mL collagenase type I and 4mg/mL dispase in 4mL PBS
containing 110U/mL penicillin, 100μg streptomycin and 0.6mL claritromycin at
500μg/mL for 1 hour at 37° (all from Invitrogen, CA). The solution was filtered
with 70μm Falcon strainers and cultivated until sub-confluent for 8 passages,
then cells were sorted by FACS (Becton Dickinson), San Jose, CA; cells were
finally tested for the markers CD166, CD81, CD105, CD34, CD45, CD14. The
cells were differentiated into osteoblasts using osteogenic medium composed
of Αmem with 10% Fetal Bovine Serum, 10Mm β-glicerophosphate, 10Nm
dexamethasone and 50 Μm ascorbic acid-2-phosphate, cell viability tests were
performed with MTT. Cells were divided into two groups: one of the groups
(group GL) received 3J/cm2 low level laser radiation (830 nm/80Mw) every two
days from the fourth day until 22nd day and the second group (group GC) was
a control group that did not receive laser radiation. RT-PCR and PCR were
performed to detect any variation between the two groups using primers of
genes linked to bone lineage initial differentiation: runx-2 and Stro-1.
Results: The results showed variation between the two groups with expression
of the gene runx-2 in the group GL before the group GC.
Conclusions: Laser radiation can have relation with the velocity of the
differentiation of DPMSC.
P50 (69)
DEVELOPMENT OF THE PROBLEMS oF TOLERANCE OF METALLIC
PROSTHESIS IN HUMAN BODY
P. Agapi, D. Bolcioni, A. Cattani, D. Cattani, F. Fabbri F. Ortolani, G. Pallotti
Univ. Bologna, Italy; Univ. Plymouth, U.K; Major Hospital Bologna, Italy
Problems with patients who have no tolerance to metallic prosthesis in their
bodies are here presented, examined and discussed.
Expositions: We are investigating the case of great importance of a patient with
a metallic prosthesis in her structures of the femoral bones having continuous
pain generated by the electromagnetic fields of mobile communications.
Discussion: We have found, after a series of accurate measurements done
during scientific investigation of our research, the cause of the pain is generated
by the the fact that the metallic prosthesis, although these are not ferromagnetic
but only electrical conductors; such elements nevertheless are properties of
receiving antennas for electromagnetic radiation crossing the space near the
human bodies.
Therefore the electric field of the radiation is travelling up and down along the
prosthesis and may interfere with the bone via piezoelectricity. These effects are
function also of the geometry and dimensions of the receiving and supporting
bone of the patient. So in the patients femur could generate mechanical waves
able to cause longitudinal, axial and torsional mouvements able to excite the
Pacini’s mechanical nociceptors.
P51 (151)
ROLE OF MESENCHYMAL STEM CELLS AND BUTYRIC/HYALURONAN
ESTERS IN RENAL RECOVERY AND ANGIOGENESIS AFTER ACUTE
KIDNEY INJURY IN A RAT MODEL
E. Della Bella1, F. Bianchi2, G. La Manna1, M. Tsivian3, F. Neri3, E. Olivi2,
S. Cantoni2, G. Pasquinelli4, G. Cenacchi4, M.P. Scolari1, C. Ventura2, S. Stefoni1
1
Nephrology, Dialysis and Renal Transplant Unit; 2Lab. Of Molecular Biology
and Stem Cell Engineering; 3Dept. of Surgery and Transplantations; 4Dept. of
Experimental Pathology, S. Orsola University Hospital, Bologna, Italy
Objectives: Acute kidney injury (AKI) is a major health-care condition with
limited treatment options. In this context, employment of Mesenchymal Stem
Cells (MSC) could represent an alternative approach for the treatment of renal
failure. It has been demonstrated that hyaluronan monoesters with butyric acid
(HB) can induce differentiation of MSC towards a metanephric and endothelial
phenotype. Thus, we investigated the effects on angiogenesis of HB-treated
and untreated human MSCs from fetal membranes (FMhMSCs) after induction
of ischemic AKI in an experimental model.
Methods: Ischemia reperfusion injury was induced by bilateral clamping of renal
pedicles in 24 rats, then HB-treated of untreated FMhMSCs were injected in
the cortex of left kidneys. Animals were followed for 7 days until sacrifice. We
assessed renal function and damage was graded by light microscopy. Electron
microscopy was performed to observe inflammatory cellular damage and
neoangiogenesis. Analysis of endothelial differentiation was performed also by
immunostaining of sections with anti-Vwf, CD34 and CD105 antibodies.
Results: FMhMSCs induced an accelerated renal function recovery and HB-
treated rats had additional beneficial effects. The clinical data were confirmed
by histology, showing less severe alterations in cell-treated kidneys. FMhMSCs
could not be detected in kidneys, but we observed enhancement in capillary
457
Int J Artif Organs 2010 ; 33 ( 7): 458
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
formation and ultrastructure showed a minor extent of phlogosis in kidneys
administered with HB-treated cells.
Conclusions: MSCs probably act in a paracrine way to induce retrieval of
ischemic AKI, promoting neoangiogenesis and lowering inflammation. These
results suggest that FMhMSCs could be useful in the treatment of AKI and the
utilization of HB could enhance the effects of the cells.
P52 (190)
NEW ALPHA-GAL REMOVAL ASSAY: PRESENCE AND DISTRIBUTION OF
THE EPITOPE BEFORE AND AFTER CELL REMOVAL FROM XENOGENEIC
HEART VALVES
F. Naso, A. Gandaglia, L. Iop, M. Spina, G. Gerosa
University of Padova, Padova, Italy
Objectives: The aim of this study is to develop an ELISA Alpha-Gal soft-tissue
assay for the quantification of the epitope in xenogeneic heart valve substitutes
after cell removal by detergent-based (TriCol) or other equivalent procedure.
Methods: Aortic and pulmonary leaflets both native and after cell removal, are
subjected to enzymatic digestion preserving the carbohydrate components and
subsequently reacted with a specific primary Alpha-Gal monoclonal antibody
(M86). The determination of unbound primary antibodies is revealed by a
secondary HRP-conjugate. The amount of Alpha-Gal epitope was compared
with a standardized source: rabbit erythrocytes. Each leaflet was also divided
into four regions with the aim of investigating the possible contribution of the
endothelial cells due to a differential microvessel density pattern.
Results: Results confirmed a different epitope distribution in native aortic
and pulmonary leaflets: 4.33*10E11 to 6.78*10E11 each 10mg of wet tissue
respectively. The decellularization completely removed the epitope thus
providing materials suitable for human xenotransplantation, cell repopulation
and tissue remodeling according to the cardiovascular implants guidelines
(ISO 5840). Sampling of specific zones in native valves, revealed a differential
Alpha-Gal distribution within and between the different leaflets. The pattern
was consistent with the immunofluorescence analysis and was unrelated to the
known microvessel density distribution.
Conclusions: This ELISA test allows specific quantification of Alpha-Gal content
in soft-tissues and could be further developed in order to determine the level of
residual unmasked xenogeneic antigens in current bioprosthetic devices. Very
likely the use of such ELISA test could be extended for exploring tissue and
organ xenotransplantation compatibility.
Artificial pancreas
P53 (31)
INSULIN PUMP AND CONTINUOUS GLUCOSE MONITORING: A STEP
FORWARD TO ARTIFICIAL PANCREAS
G. Petrovski, C. Dimitrovski, M. Bogoev, I. Ahmeti
Clinic of Endocrinology, Diabetes and Metabolic Disorders Medical Faculty,
University “Sv.Kiril I Metodij”, Skopje, R. Macedonia
Objectives: The objective of this study was to evaluate the efficacy and safety
of CSII (continuous subcutaneous insulin infusion) and continuous glucose
monitoring (CGM) in type 1 diabetics on pump therapy in Macedonia.
Materials and Methods: The study was performed at Clinic of Endocrinology in
Skopje in the period 2004-2009. Insulin pump was initiated in diabetics with poor
metabolic control. CGM was performed if HbA1C was higher than 9%. HbA1c,
severe hypoglycemia (SH), and ketoacidosis (DKA) in the year before CSII were
compared with corresponding values during two-year pump treatment.
Results: Fifty-two (24 male, 28 female), aged 16.5±8.4 years with type 1
diabetes were included in the study. Mean HbA1c from 9.4±1.1% in one year
pre-pump period decreased to 6.7±0.9% two years after CSII. The rate of SH
and DKA was reduced after transition to pump in the two years.
Conclusions: Insulin pump is an effective and safe treatment in patients with
type 1 diabetes for achieving satisfied metabolic control. CGM can fine-tune the
glucose fluctuations in brittle diabetes with achieving better metabolic control.
Integrated CSII and CGM is a step forward to close loop insulin pump in the
very near future.
458 © 2010 Wichtig Editore - ISSN 0391-3988
P54 (143)
CONTINUOUS GLUCOSE MONITORING IN TYPE 1 DIABETICS CAN
IMPROVE METABOLIC CONTROL
G. Petrovski, I. Ahmeti, K. Adamova, B. Jovanovska
Clinic of Endocrinology, Medical Faculty, Skopje, R. Macedonia
Objectives: To determine 3-day glucose profile is sufficient to improve metabolic
control in the type 1 diabetics.
Materials and Methods: Fifty-four type 1 diabetics (male 21, female 33, mean
age: 24.8±7.6 years) were included in the study at Department of outpatients in
Clinic of Endocrinology-Skopje. Mean HbA1c was 8.7±1.6%. All patients were
treated with intensive insulin therapy (4 or 5 daily injections). CGMS (Minimed
CGMS gold) was performed for 72 hours. Individual patient education was
performed on the results from 3-day glucose monitoring for food, physical
activity, self-control adjustment of the insulin therapy. Three months later HbA1c
was performed.
Results: CGMS profiles verified blood glucose excursions unrecognised by self-
monitoring measurements in all patients. Eleven patients were found to have
the Dawn phenomenon. Individual patients education recommended: change
in short acting insulin (28 patients), change in intermediate insulin (18 patients),
change in treatment of hypoglycaemia (11 patients), night-time change for
intermediate insulin due to Dawn phenomenon (10 patients), modification of
regimen for glycemic food (35 patients) and alteration on approach for physical
activity (14 patients). HbA1c was performed two months after CGMS and
showed improvement of 1.1±1.9%.
Conclusions: CGMS (3-day glucose monitoring) with special recommendation
obtained from data can improve HbA1c.
P55 (138)
Sensor-augmented pump improves diabetes control
G. Petrovski, C. Dimitrovski, B. Jovanovska, K. Adamova
Clinic of Endocrinology, Diabetes and Metabolic Disorders, Medical Faculty,
Skopje, R. Macedonia
Objectives: To describe the challenges and outcomes of continuous
subcutaneous insulin infusion (CSII) with glucose sensor in type 1 diabetes.
Methods: A case study on patient with brittle type 1 diabetes treated with smart
pump at the Clinic of Endocrinology in Skopje.
Results: Smart pump (Continuous glucose sensor and continuous insulin
infusion) was initiated to improve metabolic control in 2-year old girl with 1 year
history of brittle diabetes. During 2 years of CSII therapy, HbA1c levels dropped
from 8.7 to 6.2%, two years after therapy. Mean Hb1c in the last year of therapy
was 6.2±0.8%. There were no severe hypoglycemia and occasional postprandial
hyperglycemias were detected in the first 3 months on CSII, where she and her
family learned the practical issues of carbohydrate counting. Physically active
lifestyle was obtained. During her two years on CSII, she successfully manages
her diabetes.
Conclusions: Smart pump can be initiated and used effectively in brittle type 1
diabetes to improve metabolic control and quality of life. CSII therapy can help
type 1 diabetics to achieve and sustain metabolic control.
P56 (251)
INTRA-SUBJECT VARIABILITY OF THE HEMOGLOBIN GLYCATION RATE
IN HEALTHY VOLUNTEERS
P. Ladyzynski1, J.M. Wojcicki1, M.I. Bak2, S. Sabalinska1, J. Kawiak1, P. Foltynski1,
J. Krzymien2, W. Karnafel2
1
Nalecz Institute of Biocybernetics and Biomedical Engineering PAS, Warsaw,
Poland; 2Department and Clinic of Gastroenterology and Metabolic Diseases
WMU, Warsaw, Poland
Objectives: Concentration of the glycated hemoglobin A1c (HbA1c) is the
most prevalent index of the long-term metabolic control. It is considered that
HbA1c is formed in a non-enzymatic reaction during the whole life span of the
erythrocytes (i.e. 120 days). The kinetics of this reaction in a single erythrocyte
depends on the available amounts of hemoglobin and glucose and it can be
described by an overall reaction rate constant. The objective of the study was
to assess variability of this constant in healthy subjects.
Methods: The study group consisted of 10 volunteers (8 females and 2 males)
with no diabetes or any other metabolic disorders diagnosed. Average age (+/-
SD) was equal to 51.6 +/- 12.6 years. In each subject glucose concentration
was continuously monitored in the interstitial fluid in three periods lasting for 3-5
days each, during 2 months preceding HbA1c testing. Based on these data, two
averaged daily glycemia profiles were estimated, one for the working days and
the other for weekends. These profiles were used to extrapolate 120-day-long
Int J Artif Organs 2010 ; 33 ( 7): 459
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
glycemia course which was applied to estimate individual hemoglobin glycation
rate constant for each subject.
Results: Average (+/-SD) glycation rate constant was equal to 1.394 +/- 0.128
x 10e-9 l mmol-1 s-1. Shapiro-Wilk’s test demonstrated that distribution of the
obtained rate constants can be considered to be the normal distribution (p >
0.6). Coefficient of variation of the individual rate constants was equal to 9.2%.
This value comprises a component related to the intra-subject variability of the
individual rate constants as well as a component connected with analytical and
calculation inaccuracies.
Conclusions: Taking into account all the sources of variability of the individual
hemoglobin glycation rate constants the obtained results suggest that the intra-
subject variability of the rate of HbA1c formation is insignificant.
P57 (318)
C-IMT in type 2 diabetic patients: A survey on factors of
influence
M. Bosevski
Faculty of Medicine, University Cardiology Clinic, Skopje, R. Macedonia
The study was aimed to determine factors of carotid intima-media thickness
(C-IMT) in a population of patients with type 2 diabetes (T2D). A survey was
conducted on 370 patients (mean age 60.3 ± 8.3 years and diabetes duration 8.6
± 6.2 years) with T2D and coronary artery disease. Multivariate linear regression
analysis was built to define the factors of C-IMT, when age, systolic and diastolic
blood pressure, weight, body mass index, waist circumference, glycemia, urea,
creatinine, triglycerides, total cholesterol, LDL, HDL, and non-HDL cholesterol
were put in a model. Mean C-IMT of 0.8992 ± 0.1 529 mm, and its maximal
value of 0.9905 ± 1.946 mm was detected in this study population. Regression
analysis demonstrated that mean and maximal C-IMT were independently
associated with age, blood creatinine and diastolic pressure. Maximal C-IMT
was influenced with non-HDL cholesterol.
The results have clinical value in defining target groups in patients with T2D
and: arterial hypertension, higher non HDL cholesterol and blood creatinine, and
those older to have greater probability of detecting increased C-IMT.
P58 (238)
CASE REPORT: VASCULITIS-INDUCED ACUTE KIDNEY INJURY
(AKI) ASSOCIATED WITH ACUTE PANCREATITIS COMPLICATED BY
PANCREATIC PSEUDOCYST
I. Nikolov1, L. Tozija1, D. Petronijevic1, D. Antova2, A. Asani1, P. Dzekova1,
V. Andreevski3, P. Misevska3, M. Grlickov2, V. Serafimoski2, A. Sikole1,
K. Cakalaroski1,
1
University Clinic of Nephrology; 2Rheumatology; 3Gastroenterohepatology,
Medical Faculty, University Sts Cyril and Methodius, Skopje, R. Macedonia
Objectives: Clinical manifestations of acute pancreatitis are variable, from an
abdominal moderate pain to an extremely serious multi-organ failure associated
with bacterial sepsis. Pancreatitis appearance in systemic diseases is uncommon
and can complicate the evolution and vital prognosis in these patients.
Methods: We report here a case of a 42-year-old female patient who developed
vasculitis-induced AKI and subsequently complicated by pancreatitis. Since
appearance of AKI symptoms she was admitted in ICU at Nephrology Clinic
and treated by rehydratation and diuresis stimulation, resulting in diuresis
kept around 2000ml/24h. Consequently normalization of urea and creatinine
were obtained. Skin bleedings on both feet originally appeared as petechias,
ecchymosis further transformed into haematomas and nose necrosis. Clinical
manifestation, thrombocytopenia and leucocytosis suggested vasculitis
necroticans. We started corticosteroid, anticoagulant, antibiotic treatment and
plasma substitution. Besides analysis of cANCA, antiDNA and ANA were negative
skin biopsy confirmed vasculitis. Immunosuppressive therapy was introduced.
Previous abdominal computed tomography did not show any changes of
pancreatic tissue but showed a liquid collection and air suprapancreatically.
One day after therapy initiation an intensive abdominal pain and pancreatitis-like
clinical picture appeared. Ultrasound exam of abdomen revealed an existence
of a pancreatic pseudocyst and a surgical drainage was performed resulting in
improvement of patient clinical symptoms.
Conclusions: This case shows vasculitis-induced acute kidney injury
complicated by pancreatitis and pancreatic pseudocyst and confirms the
importance of performing early diagnosis of vasculitis complications and
artificial drainage of pancreatic pseudocyst.
© 2010 Wichtig Editore - ISSN 0391-3988
Hemodialysis 1
P59 (124)
EVALUATION OF BLOOD AND DIALYSIS FLUID FLOW IN DIALYZERS
N. Sano1, T. Hashimoto2, M. Takahashi3, T. Shibamoto4
1
Sugamo Jin Clinic1; 2Dept. of Clinical Engineering (CE), Seishokai Memorial
Hospital; 3Ogasawara Clinic; 4Dept. of CE, Shyuwa General Hospital, Japan
Objectives: Blood and dialysis fluid (DF) flows in 6 dialyzers were studied to
evaluate their performance.
Methods: Six dialyzers, which membranes were a group of polysulfones, were
chosen for this study. They were APS-15E (E, Asahi Kasei Kuraray), APS-15SA
(SA, Asahi Kasei Kuraray), FX-S 140 (FXS, FMC Japan), CS-1.6U (CS, Toray),
PES-150 Sα (Sα, Nipro), PES-150Sβ (Sβ, Nipro). Method 1. Dialyzers were set
on dialysis machines and DF was flushed at 500 ml/min for 15 min until the fibers
became wet enough. 25 mL of 1% bromophenol blue was injected through a
venous side of DF. External and internal dyed appearances of dialyzers’ fibers
were observed. Method 2. Set as same as method 1, 2.5 mL of concentrated
DF A, which contained 3,850 mEq/L of Na, was injected in bolus under flushing
DF at 500 ml/min. The changes in electrical conductivity were observed at the
exit site of DF. Method 3. Priming a dialysis system using dialyzers with 1,000
mL of saline and set Crit-Line Monitor (JMS) at a venous blood line. A sham
dialysis was performed using swine blood, whose hematocrit was 30%, under
the blood flow rate at 200 ml/min and DF flow at 500 ml/min. 10 mL of saline
was injected in bolus at the arterial blood line and the diluted rate of blood was
measured by Crit-line.
Results: Fibers at exit site of DF were not dyed in E, Sβ, and CS. The fibers of
other dialyzers were homogeneously dyed. The waves of electrical conductivity
in FXS and SA were normally distributed, and those of others were not. The
diluted rate of blood was 20% in FXS and the time returning to the baseline was
also shortest among them.
Conclusions: E had non-dyed fibers and its DF flow was not homogenous from
electrical conductivity. Sα, which has channeling preventing mechanism, was
observed as homogeneous DF flow. FXS and SA had a homogeneous DF flow
because of baffle structure and channeling preventing mechanism. FXS had a
more homogenous blood flow than others because of spiral blood port.
P60 (239)
CHARACTERISTICS OF NEPHROLITHIASIS IN AUTOSOMAL DOMINANT
POLYCYSTIC KIDNEY DISEASE
I. Nikolov1,3, M. Daudon2, A. Sikole3, B. Knebelmann1
1
Dpt. of Nephrology, Necker Hospital, University Paris 5, France; 2Dpt. of
Biochemistry A, Necker Hospital Paris, France; 3University Clinic of Nephrology,
Skopje, R. Macedonia
Objectives: Nephrolithiasis is more prevalent in patients with autosomal
dominant polycystic kidney disease (ADPKD) than in general population. The
diagnosis of lithiasis in these patients is hindered by the distorted anatomy of
the polycystic kidneys and the frequent occurrence of parenchymal and cystic
wall calcifications.
Methods: A retrospective study of ADPKD patients in a referral center in
Paris, France was performed. Medical files of 208 ADPKD patients referred
to our center between 1998 and 2008 were analyzed to assess kidney stones
frequency by radiological methods and to understand its characteristics using
morphological, infra-red spectrophotometry and chemical stone analysis.
Results: We have found that 29 (13.9%) ADPKD patients had experienced
nephrolithiasis including those who had a clinical manifestation of colic pain
and/or ultrasonography, native roentgen, CT scan detection of kidney stones.
Kidney stones could be analyzed in 9 patients. The most common type of
stone was urico-dependent in 6 (66.6%) and oxalo-dependent in 2 (2.22%)
patients. One patient had a combined urico-oxalo dependent lithiasis and stone
nucleus was uric acid (type IIIb). Superficial morphology of the stones was IIIb
in 6 cases and Ib in 4 cases. Morphology of the stone nucleus section was IIIb
in 6 cases and IVa in 2 cases. Infrared spectophotometry analysis confirmed
uric acid in the nucleus of 7/9 stones. In one case, whewelite (monohydrated
calcium oxalate) was the main component of the stone (60%), whereas uric
acid represented only 30% but was the only component found in the nucleus.
Mean value for urine pH was 6.5±0.8, and mean value for urinary uric acid was
2.28±0.66mmol/L suggesting that increased urinary uric acid was not a major
determinant of stone formation.
Conclusions: Our data provide evidence that ADPKD is associated with a high
proportion of uric acid stones. The underlying pathophysiology of uric acid
stone formation in ADPKD remains to be clarified.
459
Int J Artif Organs 2010 ; 33 ( 7): 460
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P61 (33)
Adaptation of a citrate test kit from the food industry for
its application in blood and plasma
J. Hartmann, U. Fichtinger, D. Falkenhagen
Center for Biomedical Technology, Danube University Krems, Austria
Objectives: Anticoagulation (AC) with citrate is, due to several advantages
over conventional AC based on heparin and other means of AC, on its way to
become a standard procedure in extracorporeal blood purification. However,
for patients’ safety it is important to avoid citrate accumulation on the one
hand and on the other hand to decrease ionized calcium to the needed target
concentration in the range of 0.2-0.3 mM in order to achieve adequate AC as well
as to suppress complement activation. Therefore, an exact analytical method
for the monitoring of the citrate concentration in patients’ blood is mandatory.
There is no citrate test kit on the market for the measurement of citrate in blood
or plasma. Aim of our study was to adapt a test kit from the food industry for the
semi-automated system which is in use at many clinical laboratories to enable
citrate measurements in the lab as well as in the clinic.
Materials and Methods: For the development of the method, we used the
photometric test kit from Boehringer Mannheim/R-Biopharm which is based on
enzymatic reactions and is commercially available for analysis in food. The test
kit is intended for a manual procedure and needs several pipetting and time-
critical incubation steps. We reduced the recommended amounts of reagents to
enable the use in the standard caps of the Hitachi/Roche 902 autoanalyzer. We
programmed the device to follow exactly the recommended incubation times to
gain high reproducibility. FFP and fresh drawn blood were spiked with defined
concentrations of citrate to check the recovery in these media.
Results: The results show a very good recovery and reproducibility of the test.
No pre-treatment such as deproteinization or filtration was necessary.
Conclusions: We could show that the citrate test kit can be used for citrate
measurement in blood and plasma with the Hitachi/Roche 902 autoanalyzer.
This offers very high and accurate sample throughputs. Furthermore, by using
the autoanalyzer both the sample quantity as well as the reproducibility could
be increased.
P62 (83)
MIXED MATRIX MEMBRANES FOR TOXIN REMOVAL FROM BLOOD
M.S.L. Tijink, J. Sun, O. Ter Beek, S. Saiful, Z. Borneman, M. Wessling,
D.F. Stamatialis
MIRA Institute for Biomedical Technology and Technical Medicine, University of
Twente, Membrane Science and Technology, Enschede, The Netherlands
Objectives: Chronic kidney failure requires an artificial kidney treatment called
hemodialysis. However, not all uremic toxins can be removed from the blood
by dialysis and therefore morbidity and mortality of patients are still high. In this
work we develop a Mixed Matrix Membrane (MMM) which consists of adsorptive
particles imbedded into a porous polymer matrix for selective adsorption and
removal of uremic toxins from blood, combining diffusion and adsorption in one
step. A particle-free layer is also introduced on the blood contacting side of the
MMM to prevent biocompatibility problems caused by direct blood contact with
the adsorbent.
Methods: Polyethersulfone based porous MMM with activated carbon particles
and a particle-free top layer were prepared by co-casting and subsequent
liquid-liquid phase separation. The membranes were characterized by scanning
electron microscopy, clean water flux measurements and adsorption capacity
experiments with blood model solutions.
Results: Mixed Matrix Membranes with homogenous distribution of carbon
particles and with a high clean water permeability were developed. Creatinine,
a small uremic toxin, was selectively removed from a blood model solution both
via diffusion as well as adsorption by the MMM.
Conclusions: This study shows a proof of principle for Mixed Matrix Membranes
as an artificial kidney treatment. The MMM selectively removes toxins via both
diffusion and adsorption in one step.
P63 (78)
FACTORS AFFECTING AVAILABILITY OF SUPERFICIAL VEINS FOR
CREATION OF ARTERIOVENOUS FISTULAS
Y. Sato1, R. Nakazawa1, M. Miyamoto2, T. Sakurada2, K. Kimura2, H. Sasaki1,
S. Miyano1, T. Chikaraishi1
1
Department of Urologic Surgery; 2Department of Nephrology and Hypertension,
Integrated Care Center for Renal Diseases, St Marianna University School of
Medicine, Kawasaki, Japan
Objectives: Radial-cephalic arteriovenous fistulas (AVFs) at the wrist are the
460 © 2010 Wichtig Editore - ISSN 0391-3988
most preferred configuration of dialysis vascular access. However, in some
patients, we fail to construct the standard radial-cephalic AVF because of
inadequate veins. In order to clarify the factors affecting the availability of
superficial veins, we conducted the present study.
Methods: From January 2006 to December 2009, 255 patients had first-
time vascular access surgery at our institution. When the cephalic vein was
sufficiently large at physical examination (approximately 2 mm or larger in
diameter), we created a standard radial-cephalic AVF in the non-dominant
forearm (standard group). When the vein was inadequate, we created an AVF
at the other sites wherever the superficial vein was sufficient, or we used
arteriovenous grafts (non-standard group). Medical records including types of
access, age, gender, co-morbid conditions and history of complicated surgical
procedures (cardiovascular surgery, surgical removal of malignant tumor) were
retrospectively collected and analyzed.
Results: During the period we created standard AVFs in 177 patients (69%) and
non-standard accesses in 78 patients (31%). The patients in non-standard group,
in comparison with those in standard group, were significantly older (74y.o. vs
67y.o.) and more female (41% vs 26%). Non-standard group experienced more
previous complicated surgery (35%) than standard group (15%). A multiple
logistic regression analysis revealed that previous surgery negatively affects the
availability of the cephalic vein for access creation (odds ratio 2.85, 95%CI 1.50-
5.43, p=0.0013).
Conclusions: We found that a history of previous surgery is a risk factor for
failure of standard radial-cephalic AVF construction. We speculate that peri-
operative venipunctures potentially injured the superficial veins and affected the
vascular availability.
P64 (57)
THE IMPORTANCE OF K/DOQI GUIDELINE FOR INTACT PARATHYROID
HORMONE ACHIEVEMENT ON ARETERIAL CALCIFICATION PRESENCE
IN HEMODIALYSIS PATIENTS
S. Gelev1, G. Spasovski1, Z. Trajkovski2, L. Trajceska1, S. Gjulsen1, G. Andreevska-
Severova1, V. Amitov1, A. Sikole1
1
University Department of Nephrology; 2Institute of Radiology, Skopje,
R. Macedonia
Objectives: The aim of this study was to evaluate the association between the
attainment of K/DOQI guidelines for intact parathyroid hormone (iPTH) and the
presence of arterial calcification (AC) in our hemodialysis (HD) patients.
Methods: In a cross-sectional study we examined 173 patients (104 male;
mean age 54.1±13.1 years) dialyzed on average for 94.7±71.1 months. First, we
evaluated the presence of arterial intima (AIC) and arterial media calcification
(AMC) using plain radiography of the pelvis. In addition, we compared the serum
levels and the proportion of the K/DOQI guideline achieved ranges for iPTH
of the last 12 months records among the groups of patients with various AC
findings [group with AC absence (n=41), patients presented with AIC (n=61), and
patients with presence of AMC (n=73)].
Results: There was no significant difference in serum iPTH levels [155 / range
(32-486); 96 / range (12-781); 144 / range (7-1050)] between the groups of
patients. In contrast, patients without AC had significantly higher proportion of
achieved K/DOQI recommended levels for iPTH (33/80 = 41.2%) in comparison
with the patients with AIC (22/116 = 18.9%) and patients with AMC (27/127 =
21.3%) presence. Multivariate adjusted logistic regression analyses (with group
of the patients without AC as the reference value) have shown that the odds
ratio (OR) for the AIC presence [OR=0.217, CI (0.068-0.684), p=0.009], as well
as AMC presence [OR=0.133, CI (0.037-0.472), p=0.002] on plain radiograms
of the pelvis significantly decreased with the serum iPTH being within K/DOQI
recommended ranges.
Conclusions: The K/DOQI guidelines achievement is a superior indicator than
individual serum levels of iPTH in the evaluation of AC in HD patients. The K/
DOQI guidelines achievement of serum iPTH might be crucial in the routine
clinical practice for prevention of AC development in HD patients.
P65 (131)
SOLUBLE ELEMENTS OF POLYSULFONE DIALYZERS
Y. Yoshimoto1, T. Hoshino2, N. Sano3, T. Shibamoto4
1
Dept. of Clinical Engineering (CE), Tokyo Med. & Dent. Univ. Hospital; 2Dept. of
CE, Meirikai Chuo General Hospital; 3Sugamo Jin Clinic3; 4Dept. of CE, Shyuwa
General Hospital, Japan
Objectives: Polyvinylpyrrolidone (PVP) is added to Polysulfone (PS) dialyzers.
However, it is not clear how soluble elements are eluted, or how much those
concentrations are, when PS dialyzers are used.
Materials and Methods: Subjects were APS-15E (E, Asahi Kasei Kuraray),
Int J Artif Organs 2010 ; 33 ( 7): 461
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
APS-15SA (SA, Asahi Kasei Kuraray), PS-1.6 UW (UW, Kawasumi), FX-S 140
(FXS, FMC Japan), CS-1.6U (CS, Toray), TS-1.6UL (TS, Toray), PES-150 Sα (Sα,
Nipro). Sample 1 was pre-filled water of subjects. If subjects were dry, saline,
which was filled in the fibers of dialyzers for 24 hours, was used as sample 1.
Sample 2 was 1,000 mL of saline, with which fibers were rinsed at 200 ml/min.
Sample 3 was 1,000 mL of saline, which was circulated in fibers at 200 ml/
min for 240 min after drained the pre-filled water inside and outside of fibers.
Potassium permanganate reducing substance (PP), absorbance of ultraviolet-
visible spectrophotometry (AUV), and PVP were measured of/in those samples.
Nitrogen concentration of each fiber was measured using nitrogen trace analyzer
as PVP in the dialyzers’ membrane. β2-Microglobulin (β2-MG) clearance was
measured for subjects.
Results: PP of sample 1 excluding FXS and CS was higher than 1 mL, which
is recommended standard. Especially, that of E was 3 times as high as that of
SA, UW, and Sα. AUV in sample 1 of SA, TS, UW, Sα, and E was higher than
0.1. That of E was twice as high as that of others. That of CS and FXS was less
than 0.1. PVP in sample 1 of UW was 70 μg/mL, that of Sα was 40 μg/mL, and
that of E was 30μg/mL. That of TS, CS, and FXS was very low. Sample 2 and
3 of all materials were not detected soluble elements. PVP concentration in the
dialyzers’ membrane was low in CS, PS, FXS, and Sα. That in TS and E was
high and two times of that in PS.
Conclusions: Soluble elements from materials differed by themselves. β2-MG
clearance has a significant correlation with PVP concentration in the dialyzers’
membrane.
P66 (272)
diabetics on dialysis in republic of macedonia: a nationwide
epidemiological study
M. Polenakovic1,2, A. Sikole2, I.G. Nikolov2, D. Georgiev1, G. Selim2, P. Dzekova
-Vidimliski2
1
Macedonian Academy of Sciences and Arts, R. Macedonia, University Clinic of
Nephrology, Medical Faculty, Skopje, R. Macedonia
Objectives: Dialysis treatment of diabetic patients is complex, expensive, and
exerts excessive burden on the health budgets of the affected countries.
Methods: We performed a nationwide precise observational study with aim to
analyze diabetics on dialysis in all dialysis centers in the Republic of Macedonia
(RM) in 2002 and in 2006.
Results: Prevalence of HD patients in RM was 1114 vs 1074 in 2002 and 2006,
respectively. From these, 109 (9.78%) vs 115 (10.71%) had DM in 2002 and
2006, respectively. Mean age of the patients was 58±10.29 (56±10.49 males and
60±9.56 females) vs 56.5±10.71 (55.06±8.82 males and 57.92±12.56 females)
in 2002 and 2006, respectively. Mean age of DM1 patients was 47±11.6 y. vs
45±7.32 y., with a DM history of 16.2 ±9.7 vs 24.07±11.07, in 2002 and 2006,
respectively. Mean age of DM2 patients, was 60.37±8.33 y. vs 61.14±10.23 y.
with a DM history of 13.4±8.1 y. vs 14.18±8.42, in 2002 and 2006, respectively.
Mean Body Mass Index (BMI) was 26.4 vs 23.49±4.74 kg/m2 in DM1 and
25.5 vs 24.77±3.70 kg/m2 in DM2 patients in 2002 and 2006, respectively.
Most common co-morbidity was hypertension, 91% vs 80.87% in 2002 and
2006, respectively. 40% vs 29.57% of patients had a positive family history of
hypertension. Most frequent macro-vascular complications included: pectoral
angina – 19% vs 1.12%; myocardial infarction – 5.4% vs 1.12%; intermittent
claudication - 10% vs 2.25% and cerebrovascular accident – 8% vs 8.70% in
2002 and 2006, respectively.
Conclusions: Prevalence of diabetics on dialysis in the Republic of Macedonia
did not increase in the period from 2002 to 2006. Early detection of diabetic
nephropathy by primary care physician as well as collaborative treatment of
diabetologist, nephrologist, cardiologist and ophthalmologist before and during
dialysis is very important for improving treatment and survival of diabetic
patients on dialysis.
P67 (231)
RELATIONSHIP BETWEEN THROMBOSIS OF ARTERIO-VENOUS FISTULA
AND CAROTID ATHEROSCLEROTIC LESIONS IN HEMODIALYSIS
PATIENTS
S. Pavleska1, S. Gelev1, G. Spasovski1, S. Dzikova1, S. Tosev2, A. Onceski1,
P. Dejanov1, V. Gerasimovska1, L. Trajceska1, G. Selim1, V. Amitov1, A. Sikole1
1
University Clinic of Nephrology; 2University Clinic of Cardiology, Skopje,
R. Macedonia
Objectives: The aim of this study was to compare the carotid atherosclerotic
lesions in hemodialysis (HD) patients according to the number of previous
arterio-venous fistula (AVF) thrombosis.
Methods: In a cross-sectional study we examined 112 HD patients (65 men;
© 2010 Wichtig Editore - ISSN 0391-3988
mean age 51.7±14.3 years; HD duration 98.4±59.6 months). Primarily, we
evaluated the presence of the atherosclerotic lesions using high resolution
B-mode ultrasonography of the common carotid arteries (CCA). Then we
compared the various findings of atherosclerotic lesions among the patients
arbitrarily divided in groups according to the number (more than two; one to
two; zero) of previous AVF thrombosis.
Results: Patients with more than two AVF thrombosis had significantly increased
intima media thickness (1.55±0.19 mm vs 1.44±0.21mm and 1.39±0.18mm,
p<0.05) and increased internal diameter (7.81±0.95mm vs 7.28±0.94mm and
6.74±0.92mm, p<0.01) (ID), as well as higher frequency of atherosclerotic
plaques (77.4% vs 49.3 and 21.7%, p<0.001) and calcified (51.2%vs 33.8 and
11.9%, p<0.001) intimal plaques in comparison with the other groups. Patients
with one to two AFV thrombosis compared to those without previous thrombosis
of AVF had significantly higher presence of atherosclerotic plaques (49.3 vs
21.7%, p<0.005) and calcified intimal plaques (33.8 vs 11.9%, p<0.005). There
was no statistical difference in intima media thickness and internal diameter
values between the groups of patients having one to two and patients without
previous AVF thrombosis.
Conclusions: The carotid atherosclerotic lesions in HD patients are associated
factors for frequent occurrence of AVF thrombosis.
P68 (56)
ANTI-HEPATITIS C VIRUS ANTIBODY POSITIVITY AND RELATIONSHIP
WITH ARTERIAL CALCIFICATION PRESENCE IN HEMODIALYSIS
PATIENTS
S. Gelev1, G. Spasovski1, Z. Trajkovski2, L. Trajceska1, P. Dzekova1, S. Gjulsen1,
V. Amitov1, A. Sikole1
1
University Department of Nephrology; 2Institute of Radiology, Skopje,
R. Macedonia
Although there were links between hepatitis C virus (HCV) infection and
cardiovascular diseases, the association between presence of the anti-HCV
antibodies and arterial calcification (AC) is still undetected. The aims of this
study were to evaluate the relationship of the anti-HCV antibodies positivity and
the presence of various types of AC in hemodialysis (HD) patients.
In a cross-sectional study we examined 173 patients (104 male; mean age
54.1±13.1 years) dialyzed on average for 94.7±71.1 months. Primarily, we
evaluated the presence of arterial intima (AIC) and arterial media calcification
(AMC) using plain radiography of the pelvis. Then we compared the percentages
of the anti-HCV antibody positive patients among the groups with various AC
status [group with AC absence (n=41), patients with AIC presence (n=61), and
patients with presence of AMC (n=73)].
Patients with AIC presence were more frequently anti-HCV antibody positive
(47/14 = 77.1% vs 21/20 = 51.2%; p=0.009) in comparison with the patients
without AC findings on their radiograms. At the same time, patients with AMC
presence were also more frequently anti-HCV antibody positive (52/19 = 73.2%
vs 21/20 = 51.2%; p=0.024) in comparison with the patients with absence
of AC. In univariate logistic regression analysis anti-HCV antibody positivity
was associated with the radiograms presence of AIC [OR=2.274, CI (1.242-
4.184), p=0.007], as well as with the presence of AMC [OR=1.968, CI (1.112-
3.348), p=0.02]. But, multivariate adjusted (with HD vintage) logistic regression
analyses did not identify anti-HCV antibody positivity as a factor independently
and significantly associated with the presence of both AIC and AMC in our HD
patients.
Conclusions: Anti-HCV antibody positive HD patients are more frequently
associated with the presence of AC on their plain radiograms of the pelvis.
Anti-HCV antibody positivity is not identified as a factor independently and
significantly associated with the radiograms presence of AC in HD patients.
Hemodialysis 2
P69 (176)
IMPORTANT FACTORS FOR OPTIMIZED BLOOD PRESSURE CONTROL IN
HEMODIALYSIS PATIENTS
G. Severova-Andreevska, L. Trajceska, P. Dzekova, V. Pusevski, S. Gelev,
G. Selim, V. Amitov, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Most of the patients on hemodialysis (HD) have arterial hypertension (AH). They
need medication and dietary interventions for better control of their AH. It is
well-known that lower interdialytic weight gains (IDWG) may also contribute to
good regulation of the AH. The aim was to investigate the important factors for
461
Int J Artif Organs 2010 ; 33 ( 7): 462
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
adequate control of AH in our patients on hemodyalsis.
Materials and Methods: 76 patients on HD, with an average age of 58.5 years
were investigated. Patients with blood pressure above 160/90 mmHg, measured
at home, were considered as hypertensive. All patients were evaluated for
adherence to antihypertensive therapy; IDWG, predialysis hematocrit (Ht) and
an average amount of NaCl 20% given during HD sessions were also measured.
Additionally, the total body water and daily salt intake were calculated. For
statistical analysis, the multivariate logistic regression model from the SPSS
statistic programme was used.
Results: Statistically significant association was found for the adherence to
antihypertensive therapy (p= 0.000), IDWG (p = 0.016), daily salt intake (p= 0.017)
and age (p = 0. 05) in the multivariate model. No significant correlation was found
for the total body water, Ht and amount of NaCl 20% given during HD.
Conclusions: Our results suggest that adherence to the antihypertensive
therapy, IDWG and daily salt intake may be the most powerful predictors for
better control of the blood pressure in patients on HD.
P70 (179)
THE CALCULATED TOTAL BODY WATER AND CLINICAL SIGNS FOR
OVERHYDRATION IN PATIENTS ON HEMODIALYSIS
G. Severova-Andreevska, L. Trajceska, P. Dzekova, V. Pusevski, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: The total body water (TBW) in the adult population is about 60%
of the body weight. It varies with regard to gender and the percentage of fat
tissue. In anuric and oliguric hemodialysis (HD) patients (pts), interdialysis fluid
intake may change the TBW percentage. If interdialysis weight gain (IDWG)
exceeds 4–4.5% of the dry weight (DW), as a result of high fluid intake, signs
of overhydration (OH) can appear. The aim was to investigate whether the
calculated TBW is associated with the clinical signs for OH in pts on HD.
Materials and Methods: In 75 pts on HD, with an average age of 58.5 years,
the TBW was calculated using Watsons’s formula. According to the median level
of TBW, they were divided into low and high TBW pts. They were observed
for 6 months and the mean monthly values for the hematocrit (Ht) , IDWG and
amounts of NaCl 20% given during HD were noted. The daily salt intake (DSI)
was also calculated. All pts were additionally evaluated for approaching the
DW, hypertension, night dyspnea and collapses during the HD. Chest X-ray and
heart ultrasound (HU) were performed.
Results: The median level of the TBW was 29.97 L. When the DSI and IDWG
were also dichotomized by their median levels, significantly higher amounts of
TBW were found in the pts with higher DSI OR 6.0:[CI 2.16 – 16.75], p = 0.0001
and in those with a higher IDWG OR 4.6:[CI 1.7 – 12.5], p = 0.002. What’s more,
higher amounts of TBW were determined in pts with night dyspnea OR 5.5 :[CI
1.1 – 28.2], p = 0.039, pts with a high Ht OR 3.08 :[CI 1.1 – 8.3], p = 0.031 and
chest X-ray findings for OH p = 0.059. With the use of the multivariate model,
the daily salt intake (p = 0.0001, ß = 0.549) and IDWG (p = 0,0001, ß = 0.545),
were determined as the most powerful predictive factors for total body water.
Conclusions: The calculated TBW is well associated with IDWG and the DSI.
Positive assotiation was found concerning night dyspnea and chest X-ray
findings, which can be the signs of OH. Other studies are needed to correlate
the TBW with chronic OH.
P71 (209)
TYPE OF VASCULAR ACCESS AND C-REACTIVE PROTEIN (CRP) LEVELS
IN CHRONIC HEMODIALYSIS PATIENTS
V. Persic, R. Ponikvar, S. Dejanova, J. Kovacˇ, A. Marn-Pernat, B. Knap,
V. Premru, M. Benedik, J. Varl, J. Gubenšek, B. Kersnicˇ, J. Buturovic-Ponikvar
Dialysis Center Zaloska, Department of Nephrology, University Medical Center,
Ljubljana, Slovenia
Objectives: The majority of patients with chronic kidney disease have evidence
of chronic inflammation. In dialysis patients, inflammatory biomarkers (CRP,
interleukins) are elevated and predict poor outcomes.
The aim of our single-center cross-sectional study is to compare serum levels of
CRP in chronic dialysis patients with different kind of vascular access.
Methods: 214 chronic dialysis patients, 120 males, aged 64±15 years being
on chronic hemodialysis for 6.6±7.5 years were included. CRP levels from
regular month laboratory values from July 2009 were analyzed, and type of
vascular access at that time was recorded – native arteriovenous fistula (AVF),
polytetrafluoroethylene (PTFE) graft or catheter. Catheters used in our center
were temporary single or double lumen, jugular or femoral, non-cuffed, locked
with 30% citrate. In all patients with catheters, exit site was described and
classified into three groups: A – exit site without signs of infection, B – redness
around exit site, without purulent exudate, C – infected exit site, purulent
462 © 2010 Wichtig Editore - ISSN 0391-3988
exudate.
Results: Vascular access in the majority of patients - 74% (158/214) - was
native AVF. 6% (14/214) had PTFE graft and 20% (42/214) had catheter. Average
CRP level was 10±14 mg/L with differences between those 3 groups of vascular
access (AVF 8.5±12.1; PTFE graft 7.8±6.2; catheters 18.3±29.8 mg/L). In 47%
of patients, CRP level was equal or bellow 3 mg/L. The higher level of CRP was
observed in patients with catheters, but clinical manifestations of infection were
rare. In this group, the lowest percentage (26%) of patients with CRP≤3 mg/L
was noticed. In 8/42 (20%) patients, there was a redness around the exit site
described but without purulent exudate.
Conclusions: CRP levels in chronic hemodialysis patients with native AV fistula
and PTFE graft were low and not signifiicantly different. However, patients
having hemodialysis catheters had significantly higher CRP level.
P72 (308)
ECHOCARDIOGRAPHY INVESTIGATION OF PULMONARY HyPERTENSION
IN PATIENTS UNDERGOING HEMODIALYSIS AND GENERAL POPULATION
P. Avramovski1, P. Janakievska1, M. Koneska2, S. Siljanovski1, A. Sikole3
1
Clinical Hospital, Bitola, R. Macedonia; 2Medical Center, Prilep, R. Macedonia;
3
Clinic of Nephrology, Faculty of Medicine, Skopje, R. Macedonia
Objectives: Pulmonary hypertension (PH) is a well known uncommon
complication of end-stage renal disease (ESRD). Doppler echocardiography
is commonly used to estimate systolic pulmonary artery pressure (sPAP) and
to diagnose pulmonary hypertension from the peak velocity of a tricuspid
regurgitated jet. The aim of this study is to evaluate and compare the incidence
of PH in ESRD versus incidence of PH in general population.
Materials and Methods: We estimate 46 ESRD patients (19 males and 29
females, mean age 51±8.5 the mean duration of HD 72±34 months) and 30
subjects from general population (12 males and 18 females, mean age 54±6.1).
Exclusion criteria were chronic obstructive lung disease, pulmonary embolism,
parenchymal lung disease, primary PH and severe mitral or aortic disease. All
patients underwent full clinical evaluation (echocardiography, chest radiography)
and laboratory investigation (serum calcium, phosphorus, alkaline phosphatase,
PTH, lipids and hemoglobin). PH was defined as pulmonary artery systolic
pressure (PAP) > 30 mmHg as determined by Doppler echocardiography used
ultrasound machine Toshiba SSA-340A and modified Bernoulli equation.
Results: PH was detected at 10 ESRD patients (21.73%), sPAP >35 mmHg was
detected in 4 ESRD patients with PH (40%) and sPAP >40 mmHg was detected
in 6 ESRD patients (60%). Of those with PH, LVH was seen in 4 patients
(40%), and valvular calcifications in 3 patients (30%). PH was detected in only
2 subjects from general population (6.66%) with sPAP <40mmHg. The mean
level of PTH in ESRD patients was 249±53 pg/mL versus mean level in general
population 52±17 pg/mL which did not correlate with the presence of PH.
Conclusions: We conclude that the patients with ESRD receiving regular HD
have greater morbidity of PH than general population, which is not related to the
PTH level or other metabolic abnormalities.
P73 (91)
MICROINFLAMMATION IS IMPROVED BY HIGHER ADVANCED GLYCATION
END PRODUCTES FOOD INTAKE IN DIALYSIS PATIENTS OVER TIME
L. Trajceska, P. Dzekova, S. Gelev, G. Selim, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: The effect of exogenous advanced glycation end products (AGEs)
on inflammatory reactions in vivo is still a matter of debate.
Methods: In a prospective study on 87 stable hemodialysis patients we have
analyzed the influence of AGEs food intake on C-reactive protein (CRP) in one
year. Excluding criteria: acute infections. Daily AGEs intake was estimated by
Goldbergs’ tables (J Am Diet Assoc. 2004) on the start of the study and patients
were assigned to two groups by median levels of the AGEs intake (cut-off 8485
KU/day), as high (N=49) and low (N=48) AGEs group. Nutritional status (NS)
was assessed by body mass index (BMI), subjective global assessment (SGA)
and standard body weight (SBW). Groups were matched for gender, age, NS,
vintage, CRP level, hemoglobin, adequacy, type of vascular access, presence of
diabetes and Hepatitis C antibodies. Comparison of the CRP levels was made
on two points, at the start and end of study with Mc Nemar test.
Results: The AGEs intake and CRP levels correlated insignificantly with each
other within both groups on the both study points. Patients with high AGEs
intake did not differ from those with low intake for CRP in the two points. For
the high AGEs group the odds for high CRP level (above median value) were 19
times lower after one year when compared with first point of analyze, (OR 19.5
CI: [2.28 – 166.38], p=0.001). When the presence of inflammation (as CRP above
median) was adjusted for intake of AGEs with paired approach, in patients with
Int J Artif Organs 2010 ; 33 ( 7): 463
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
higher AGEs intake, the inflammation was lower after one year for 3.45 times,
CI:[1.01 – 11.8] , P=0.0001.
Conclusions: The presence of high AGEs food intake was not linked to increased
microinflammation. Over time, the inflammatory status of patients with higher
AGEs intake improved. The traditional diet of our patients and generally low
AGEs food intakes might be the explanation for the lowering microinflammation
over time.
P74 (315)
Extrarenal disease activity in patients with lupus nephritis
and chronic renal disease and patients on hemodialysis
M. Milovanceva-Popovska, L. Grcevska, S. Dzikova, V. Ristovska, A. Sikole
University Clinic of Nephrology, Medical Faculty “Sts Cyril and Methodius”,
Skopje, R. Macedonia
It is considered that development of chronic renal disease (CRD) in patients
with Systemic lupus erythematosus (SLE) and lupus nephritis (LN) results
with significant decrease of the activity of the disease. It is believed that
immunosuppressive effect of the uremic state and changes in the immune
response in patients on chronic hemodialysis (HD) lead to continuous
suppression of the extrarenal disease activity.
The aim of the study was to examine the impact of CRD and HD on the activity
of the underlying disease in patients with SLE and LN.
We examined thirty-eight patients with SLE, LN and CRD. Patients were divided
into two groups. The first group (n=23) was composed of patients with CRD
defined as serum creatinine >200 micromol/L for periods longer than 6 months.
In the second group (n=15) there were patients on HD for periods longer than 6
months. We considered that patients had the activity of the disease if they had
temperature, butterfly-shaped rash across cheeks and nose, serosytis, muscle-
skeletal and/or central nervous system (CNS) involvement. 67% of patients with
CRD and 54% of patients on HD had activity of the disease. Most patients
had complement changes (n=17), 8 had muscle-skeletal symptoms, 11 had
thrombocytopenia/leucopenia, 3 had serosytis, 6 had prolonged temperatures
and one patient had CNS involvement. According to age, no difference between
the two groups was detected. Duration of the LN was shorter in patients with
CRD (6 years) than in patients on HD, 8.5 years.
Patients with SLE and LN with CRD or on chronic HD still have extrarenal
disease activity. They need continuous and careful monitoring and assessment
for rational therapy with low dose corticosteroids.
P75 (336)
OPTIMIZATION OF ANEMIA MANAGAMENT IN CKD PATIENTS ON
HEMODIALYSIS WITH MIRCERA IN THE INSTITUTE OF NEPHROLOGY-
STRUGA
S. Mena, M. Zabzun, T. Stojanoska, O. Murtezai
Institute of Nephrology, Struga, R. Macedonia
Objective: Methoxy polyethylene glycol-epoetin beta, continuous erythropoietin
receptor activator - MIRCERA is an innovative agent with unique receptor activity
and a long half-life (134 hours compared with 8.2 hours for epoetin). Mircera
provides effective, stable maintenance of Hb levels at extended dosing intervals
of up to once monthly.
Methods: In this analysis we examined the patients with CKD on HD who
received treatment with MIRCERA or a comparator ESA. 2 study groups were
created with the same conditions of clinical data. Group A (Mircera group) No:
11. Group B (comparator ESA group) No. 11. (Clinical data – gender, age, renal
diagnosis, duration of HD treatment, duration of ESA treatment and Hb levels
were similar). MIRCERA doses were administered S.C. 2 dose levels: 50 and
100 micro g every 2 weeks (Q2W) to attain a Hb level of 12.0 g/dL in a correction
period as well as doses of 50, 100 and 150 micro g every 4 weeks (Q4W) in
maintenance period to maintain target Hb levels of 11–13 g/dL. The observation
period was 34 weeks.
Results and Conclusions: We reached a substantial increase in Hb levels in
78% of Group A and 74% of Group B in Q2W. During the maintenance period
we maintained Hb levels in a target range in 82% in Group A and 72% in Group
B in Q4W. MIRCERA was well tolerated with a low incidence of adverse events.
No significant increase of incidence of hypertension was noticed. This study
demonstrates that MIRCERA is a potent and unique erythropoietin receptor
activator which provides a smooth and steady increase of Hb levels as well as
successful maintenance of target Hb levels in hemodialysis patients.
© 2010 Wichtig Editore - ISSN 0391-3988
P76 (305)
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY FOR BACTEReMIA
ASSOCIATED WITH TUNNELED FEMORAL CATHETERS FOR
HEMODIALYSIS
V. Gerasimovska, A. Oncevski, B. Gerasimovska-Kitanovska, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Tunneled dialysis catheters have evolved into an important option for
hemodialysis (HD) patients access. The major complications of these catheters
are catheter thrombosis and infection. The incidence, spectrum of infecting
organisms, and optimal treatment for catheter-associated bacteremia (CAB)
have not been clearly established. CAB involves therapy with systemic
antibiotics and instillation of an antibiotic lock into the catheter lumen. In this
study 60 chronic HD patients (38 female and 22 male, aged 18-75-years), with
85 tunneled femoral catheters (TFC) were prospectively monitored for infection
during three years. All patients were on regular HD ambulatory (as a outpatient).
The TFC were removed if the patients had uncontrolled sepsis, other vascular
access was ready for use, or malfunction of the catheter was present. Clinical
signs of infection were monitored and blood cultures from the catheter (BCC)
and from peripheral vein (BCP) were obtained when we had a suspicion of CAB.
Patients with clinical signs of sepsis were hospitalized for further management,
whereas those with milder symptoms were managed as outpatients. All patients
with CAB were treated with a 21-day course of intravenous antibiotics and
antibiotic lock (ABL) into the catheter lumen after each HD, without catheter
removal. During this study, there were 8859 catheter days (average 136 d), with
18 episodes of CAB or 2.03 episodes/catheter days (95% confidence interval,
2-4.1/1000d). Fourteen infections (77.8%) were caused by gram-positive cocci
only, including S. aureus, Coagulasa-negative Staphylococci and Enterococcus
species. Two infections (11.1%) were caused by gram-negative rods only, and
two infections (11.1%) were polymicrobial. Three TFC were removed because
of severe uncontrolled sepsis. TFC salvage was successful in all other patients
treated with antibiotics alone. Usually used systemic antibiotics and ABL were
Vancomycin, Ceftazidim, Cefotaxim and Ciprofloxacin. We concluded that
the use of antibiotic lock in conjunction with systemic antibiotic therapy can
eradicate CAB with careful follow-up.
P77 (262)
Mortality in hemodialysis patients at the hemodialysis center
Cair - Skopje
V. Amitov, S. Gelev, L. Trajchevska, G. Severova-Andreevska, V. Pushevski,
A. Sikole
University Department of Nephrology, Skopje, R. Macedonia
This research includes analysis of 230 patients (118 males, 112 females) who
died in a period of 13 years (1997-2010). Statistical analysis by gender, age,
dialysis period, main disease and death causes are made.
According to the results, the number of died patients is by far the biggest in
2003 and 2004 (25 patients). The average age of the patients is 65, while the
average dialysis period is 7 years. The most common main diseases are diabetic
nephropathy and nephroangiosclerosis. Glomerular nephritis appears as a main
disease in the period between 2002 and 2006, and falls rapidly afterwards.
Heart diseases appear as the most common death cause (48%), followed by
CVI (32%), which has grown rapidly since the last analysis by A. Sikole and his
co-workers in 1996, when CVI made only 15% from the total death causes.
Therefore, the number of patients affected by diabetes mellitus has rapidly
grown, as well as CVI as a common death cause. This result puts up the
question whether CVI and diabetes mellitus are a consequence of hypertension
or volume dependent hypertension. According to our research, most of them
are volume dependent-ECV.
P78 (296)
Slow continuous ultrafiltration - the safe and efficient
treatment for patients with cardiac failure and fluid
overload
T. Anguseva, Z. Mitrev, D. Nikolovska, V. Kostova, I. Kirova
Special Hospital for Surgery Fillip II, Skopje, R. Macedonia
Objectives: Slow Continuous Ultrafiltration (SCUF) was first used in 1980 as an
alternative mode of fluid removal for patients with oliguric acute renal dysfunction
for whatever cause. The advantage of this treatment is that hemodynamic
parameters remain stable in the presence of significant removal of fluid.
Material and Methods: We are describing our experience in 3 patients [age:
57±9 years; 2 male, 1 female] with cardiac failure and fluid overload who had
undergone 8 sessions of SCUF. All of them had renal impairment and were
463
Int J Artif Organs 2010 ; 33 ( 7): 464
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
resistant to diuretics. Blood lines were attached to a Gambro Prismaflex.
Results: The following parameters were monitored: Blood pump (Qb): 175±26
ml/min, time (T): 393±49 minutes. Venous pressure averaged 55±24 mmHg. We
achieved ultrafiltration of 2,189±699 ml/session or 5.5±1.7 ml/hr There was no
significant change in blood pressure [systolic pre: 143±14, post: 136±13 mmHg,
not significant; diastolic pre: 87±10, post: 83±10 mmHg, not significant and
pulse rate [pre: 87±9 vs post: 84±2 per minute, not significant. Heparin dosage
averaged 275±26 IU/hr during the SCUF.
Conclusions: We conclude that SCUF is beneficial to diuretic resistant
patients with cardiac failure and fluid overload in whom dialysis treatment is
not required.
Artificial Kidney 1
P79 (161)
FLUORESCENCE OF TOTAL AND FREE FLUOROPHORES IN BLOOD
PLASMA BEFORE AND AFTER HEMODIALYSIS
G.E. Engels1, S. Arsov1, G. Rakhorst1, W. van Oeveren1, B. Stegmayr2,
R. Graaff1
1
Department of Biomedical Engineering, University Medical Center Groningen,
University of Groningen, Groningen, The Netherlands; 2Department of Medicine,
University of Umeå, Umeå, Sweden
Objectives: In end-stage renal disease (ESRD) patients’ advanced glycation
endproducts (AGEs) and AGE peptides accumulate in plasma and tissues. In
healthy controls only trace amounts are detectable in plasma. Furthermore,
plasma fluorescence (PF) correlates to the amount of plasma AGEs, therefore PF
can be used to monitor removal of plasma AGEs during dialysis. We combined
two methods for measuring PF and investigated whether this could contribute
to study differences in plasma AGE removal, and to facilitate studies on skin
autofluorescence. We applied this method to high flux (HF) and low flux (LF)
dialysis.
Methods: Plasma samples from 29 ESRD patients were collected before
and after dialysis, once during HF and once during LF dialysis. Fluorescence
of plasma samples was determined, and corrected for plasma albumin
concentration. Total PF was obtained by diluting plasma samples in phosphate
buffered saline, whereas free PF was obtained by precipitation in 2.4%
Trichloroacetic acid, followed by centrifugation. Fluorescence was measured
for three wavelength pairs for excitation and emission (330/380), (355/460) and
(370/460), with wavelengths in nm.
Results: Reductions in PF between 10 and 40% were found after dialysis
(p=0.0001). Fluorophores with excitation in the range 355-370 nm showed more
removal of free PF as compared to total PF (p=0.001). Excitation at 330 nm did
not display this result. Although there was a trend indicating more removal of
fluorescence by HF than LF (between +1 and +6% for different wavelenghts),
these differences were not significant in our study.
Conclusions: By combining both methods for measuring PF it is possible
to study AGE removal during dialysis. In our study no significant difference
between HF and LF was found. However, there are large differences in removal
of PF between the free fraction and the total fraction, which needs further
investigation.
P80 (147)
CHANGES OF REFLECTION SPECTRA IN HEMODIALYSIS
M. Koetsier1, S. Arsov1, G.E. Engels1, B. Stegmayr2, G. Rakhorst1, R. Graaff1
1
Department of BioMedical Engineering, University Medical Center Groningen
and University of Groningen, The Netherlands; 2Department of Internal Medicine,
University Hospital of Northern Sweden, Umeå, Sweden
Objectives: Skin autofluorescence (AF) is an important predictor for
cardiovascular risk in renal failure. In a previous study on skin AF in dialysis
patients, we noted that skin AF was slightly but significantly decreased after
hemodialysis. After introducing a new algorithm that corrects for the influence of
skin color, by means of variables of the skin reflection spectrum, the significance
disappeared, although fluorescence in plasma samples did decrease. The aim
of this study is to determine the differences in spectral characteristics both in
high flux (HF) and low flux (LF) dialysis.
Methods: Skin AF and reflection spectra were measured immediately before
and after HF and LF dialysis treatment in 29 end-stage renal disease patients.
Plasma samples were obtained at the same timepoints. Skin AF was defined
as the mean emission in the 420 – 600 nm range upon excitation in the 350
– 420 nm range. Reflection spectra were obtained in the 350 – 700 nm range.
464 © 2010 Wichtig Editore - ISSN 0391-3988
In the plasma samples, 460 nm fluorescence upon excitation at 370 nm was
measured. Multivariate analysis was performed to predict the decrease of
plasma fluorescence from the changes in the spectra.
Results: Skin AF was not different before and after dialysis for both dialysis
methods (p = 0.32 for HF and p = 0.18 for LF, 1-tailed t-tests) in our study,
whereas plasma fluorescence decreased after treatment (p < 0.001 for both
dialysis types). Reflection spectra were different in several aspects after dialysis.
The decrease of plasma fluorescence correlated better (R² = 0.6) with changes
in the spectra in HF than in LF dialysis (R² = 0.4).
Conclusions: Because skin AF is not decreased significantly after dialysis,
measurement of skin AF for assessing cardiovascular risk may be performed
before or after dialysis. Furthermore, the decrease of plasma fluorescence in
dialysis may be predicted by changes in the emission and reflection spectra
of the skin.
P81 (146)
IS IT POSSIBLE TO PROTECT BLOOD DURING HEMODIALYSIS?
T. Walski, K.Grzeszczuk, M. Komorowska
Institute of Biomedical Engineering and Instrumentation, Wroclaw University
of Technology, Poland; Regional Specialist Hospital in Wroclaw, Research and
Development Centre, Poland
Objectives: The interaction of blood with bioincompatible membranes of the
dialyzer, which is a part of the extracorporeal circuit during hemodialysis, leads
to activation of several cellular and non-cellular systems. It results in a massive
production and releases of Reactive Oxygen Species (ROS). Oxidative stress
increases in uremic patients and is one of the major factors contributing to the
anemia of chronic renal failure. It is known that Near Infrared Radiation (NIR)
stabilizes Red Blood Cells membrane through increasing its resistance for
destructive factors and has antioxidant properties. The present work examines
irradiated blood susceptibility to in vitro induced oxidative stress.
Methods: Whole, heparinized (10 IU/mL), bovine blood (hematocrit 20%, volume
10 mL) was incubated in a thermomix container to obtain temperature 37°C.
After that blood cells were treated with tert-butyl hydroperoxide (t-BOOH) at a
final concentration of 9 mM/L. Samples (except a control probe) were modified
by impulse sequences of Near Infrared Radiation for 30 minutes. The following
energies were applied: 0.3, 1.1, 3.8 and 12.5 J. Incubated blood samples were
gently shaken in thermomix for the next 6 hours. Hemolysis was measured.
An optimal energy was chosen and tested in vitro on blood treated circulation
in a hemodialysis machine using synthetic membrane. Blood samples (5 mL)
were collected at 0, 5, 15 and 30 minutes of hemodialysis. Osmotic fragility,
hydroperoxide levels, hematocrit, hemolysis were determined.
Results: Energy of 3.8J decelerates t-BOOH-induced RBCs hemolysis for over
30%. The results showed greater decrease in osmotic fragility during dialysis
for irradiated samples in comparison with control samples. We observed also
significant increase of hydroperoxides concentration difference between control
and NIR modified blood.
Conclusions: Suitable energy of Near Infrared Radiation prevents destructive
effects of oxidative stress in blood.
P82 (241)
HEMODIALYSIS PATIENTS AND L-CARNITINE THERAPY EVALUATION
B. Dejanova1, S. Petrovska1, P. Dejanov2, A. Sikole2
1
Institute of Physiology; 2Department of Nephrology, Medical Faculty, University
“Ss. Cirilius and Methodius”, Skopje, R. Macedonia
Objectives: The impaired homeostasis of L-carnitine in hemodialysis (HD)
patients is well known. The aim of the study was to evaluate the L-carnitine
level in HD patients under its therapy and the symptoms expression.
Materials and Methods: The patients were divided in 2 groups: I (n=20) as
a control group and II (n=17) on L-carnitine therapy. After every HD session
during 6-month period, the patients in II group were given 1gr. i.v. L-carnitine
from Sigma-tau Pharmaceutical Industry, Rome, Italy. Blood samples were
taken from the cubital vein and the L-carnitine was measured by enzyme UV
method (Roche Diagnostic GmbH, Manhaim, Germany). Before the assay was
performed, plasma was deproteinized with 0.6 mol/L perchloric acid and 1.2
mol/L potassium carbonate. The quantity of NADH was measured at 340nm and
the results were given in mg/L. The measurements were made at the beginning,
after 3 and after 6 months. After 6 month period, patients were asked for pain
in legs and ankles, muscle cramps, fatigue and pruritus. For statistical analysis,
the analysis of variance (ANOVA) was used.
Results: L-carnitine level in group II showed significant increase from 5.3 ± 1.7
mg/L to 14.7 ± 8.2 mg/L after 3 months and 16.0 ± 5.7 mg/L after 6 months
(p < 0.01). The level in the Ist (control) group remained the same during the
Int J Artif Organs 2010 ; 33 ( 7): 465
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
study. After a 6-month therapy in the Ist group the most common symptoms
remained as they were present at the beginning: pain in legs and ankles (n=13),
muscle cramps (n=11), fatigue (n=17), pruritus (n=11) while in the II group: pains
in legs and ankles (n=6), muscle cramps (n=3), fatigue (n=2) pruritus (n=12).
Apart from all symptoms, only the pruritus has not shown any improvement
during the therapy.
Conclusions: From the obtained results, it can be concluded that increased
L-carnitine level due to its therapy showed some symptoms improvement in
the HD patients which contribute to their better quality of life. However, more
studies are needed to consider beneficial effects in patients on HD.
P83 (224)
SEASON INFLUENCE ON THE ADVANCED GLYCATION END PRODUCTS
FOOD INTAKE IN DIALYSIS PATIENTS
L. Trajceska, P. Dzekova, S. Gelev, V. Pusevski, G. Selim, V. Amitov, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: Food is a possible contributing factor on advanced glication end
products (AGE) accumulation. The season could influence the food AGE intake
by offering different food products on the market and season-related customs
which influence the kinds of food and preparation methods referring to culture
and tradition.
Methods: 83 dialysis patients were included in a prospective, observational
study in two points representing spring/summer and autumn/winter season.
Dietary records for 7 days were obtained. Calories and protein intake were
calculated and AGEs intake was estimated according to Goldbergs tables
(Goldberg et al., 2004). Meals were stratified as homemade and market meals.
The last ones included snacks and fast foods. Data from the two points were
compared with paired samples T-Test.
Results: The number of homemade meals was significantly higher in the winter
period [3009 (82%) vs. 3212 (92%), p=0.01] and the marked meals in the spring
period [624 (18%) vs. 268 (8%), p=0.01]. Also, the snacks and fast foods were
more present in the summer period [550 (13%) vs. 208 (6%)], p=0.001; [183
(5%) vs. 69 (2%)], p=0.02; respectively. No differences were found between first
and second point for the daily calories, protein and AGEs intakes (32.47±10.05
vs. 32.45±7.85 kcal/24h/kg), p=0.973; (1.29±0.69 vs. 1.31±0.59 g/24h/kg),
p=0.519; (10±4.3 vs. 9.8±4.3 MU/day, p=0.064).
Conclusions: The special dietary habit due to the disease and the presence of
traditional diet among our dialysis patients promote unificant dietary pattern and
AGEs food intake through all the different seasons.
P84 (185)
DOES FOOD INTAKE OF ADVANCED GLYCATION END-PRODUCTS
INFLUENCE THEIR ACCUMULATION IN THE SKIN OF HEMODIALYSIS
PATIENTS?
S. Arsov1, L. Trajcevska2, R. Graaff1, W. van Oeveren1, P. Dzekova2, B. Stegmayr3,
A. Sikole2, G. Rakhorst1
1
Dept. of Biomedical Engineering UMC, Groningen, The Netherlands; 2Dept.
of Nephrology, Clinical Centre, Skopje, R. Macedonia; 3Dept. of Nephrology,
University Hospital, Umeå, Sweden
Objectives: To investigate the effect of diet on AGEs accumulation in
Hemodialysis (HD) Patients.
Methods: 156 HD patients were recruited for this study. Skin Autofluorescence
(AF) was used to estimate the skin AGEs accumulation which was measured
using an AGE-Reader (DiagnOptics, The Netherlands). Their Skin AF was
measured at 4 time points in a period of 18 months. Two dietary records from
the patients were obtained for 7 consecutive days: one in the summer and one
in the winter. From the dietary records the protein, calorie and AGEs food intake
were calculated; for the AGEs food intake Goldberg et al.2004 data were used.
Routine blood analysis was performed monthly and additional measurements of
Superoxide Dismutase (SOD), Myeloperoxydase (MPO), Inter-Cellular Adhesion
Molecule 1 (ICAM-1), von Willebrand Factor (vWF), and Heart-type Fatty Acid
Binding Protein (H-FABP) were performed twice a year in conjunction with the
AF measurements.
Results: The protein, calorie and AGEs intake were not significantly different
between summer and winter. The change of Skin AF in the followed period
of 18 months was 0.39±0.86. In the multiple regression model we found that
independent contributors of the increase of the Skin AF were: lower AGEs intake
at the first time point (β= -0.27; p=0.02), longer HD vintage (β=0.28; p=0.03) and
higher MPO (β=0.25; p=0.04). We also found that the protein and calorie intake
correlate negatively with the SOD (R=-0.18; p=0.05 and R=-0.21; p=0.02),
whereas the protein and calorie intake correlate positively to AGEs intake
(R=0.43; p=0.01 and R=0.42; p=0.01).
© 2010 Wichtig Editore - ISSN 0391-3988
Conclusions: Based on the AGEs intake negative correlation with AGEs
accumulation and positive with calorie and protein intake, we suggest that the
AGEs accumulation in the HD patients is mostly due to malnutrition resulting in
increase oxidative stress, rather than due to dietary AGE intake.
P85 (90)
FACTORS ASSOCIATED WITH HEMOGLOBIN VARIABILITY IN DIALYSIS
PATIENTS
A. Sikole , L. Trajceska, V. Pusevski, G. Severova, P. Dzekova, S. Gelev, G. Selim,
V. Amitov
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: Fluctuations in hemoglobin (Hb) levels in dialysis patients treated
with erythropoietin-stimulating agents (ESA), are linked to increased mortality.
This study aimed to assess the associated factors with the Hb level variability
(Hb-Var) in dialysis patients.
Methods: Hb-Var (defined as standard deviation of mean Hb levels) was
assessed in 142 dialysis patients treated with short-acting ESA, within 6 Hb
measurements during one year. Patients on dialysis less than one year were
excluded from the study. Intensity of the ESA treatment as individual ESA dosage
and iron dosage were evaluated. Rates between number of visits that required
ESA dosage change and number of those with effective dosage change of total
6 visits (RDC) were calculated. Pertinent laboratory, demographic and dialysis
data were recorded. Univariate and multivariate analyses were performed.
Results: 7% of patients maintained stable Hb level within the range (11.0-
13.0 g/dL), although 25% maintained Hb level >11.0 g/dL. In the univariate
analysis the Hb-Var positively and significantly correlated with serum transferrin
(p=0.01), iron (p=0.013) and predialysis BUN levels (p=0.027). ESA dosage, as
weekly dose per Kg of body weight was not found as good correlate of Hb-
Var (p=0.674). The shorter dialysis vintage showed positive correlation with
Hb-Var (r=0.162, p=0.0054), but the significance was lost in the multivariate
model. The multivariate analysis showed that the clinical factors associated with
variability were presence of acute blood loss (β=0.298, p=0.000), higher serum
iron values (β=0.236, p=0.002), RDC (β=0.202, p=0.009) and Hb levels out of
target (β=0.215, p=0.004).
Conclusions: EPO dose changes, blood loss and poor achievement of target
Hb levels are the determining factors of Hb-Var. More research is needed to
determine whether variability itself is an influencing factor or a marker of the
patient’s underlying condition.
P86 (79)
DOES THE SWIRLGRAFT REALLY OUTSTAND THE CONVENTIONAL
STRAIGHT GRAFT? A FULL MODEL CFD ANALYSIS.
K. Van Canneyt1, G. De Santis1, S. Eloot2, P. Verdonck1
1
bioMMeda-IBiTech, Gent University, Ghent, Belgium; 2Dept. of Nephrology,
Gent University Hospital, Ghent, Belgium
Although the arterio-venous fistula is known to be the first choice as vascular
access for hemodialysis, in case of low quality veins, an arterio-venous graft
(AVG) seems to be the best long-term alternative. AVGs however deal with
complications such as thrombosis and stenosis. The latter originate from the
incidence of intimal hyperplasia which is mainly located in regions of low wall
shear stress (WSS), such as in the venous anastomosis or in the draining vein.
The SwirlGraft (Veryan Medical, UK) claims to reduce regions of low WSS at the
venous anastomosis, based on the small amplitude helical design. While some
computational fluid dynamics (CFD) studies investigated the hemodynamics
in the helical grafts as such, we aimed to study by CFD the difference in
hemodynamics between a straight graft and the SwirlGraft in a clinical relevant
AV loop graft configuration.
Therefore, using pyFormex (www.pyFormex.org), 2 full scale models of an artery
and a vein were built, connected with a conventional straight graft (CG) and a
SwirlGraft (SG), both in a loop configuration. After a robust mesh sensitivity analysis,
simulations were performed on the fully hexahedral structured and conformal
mesh. A parabolic inlet flow (600 ml/min) entered the proximal artery while a flow
distribution was set to the outflow paths: 5% for distal artery, 5% for distal vein, and
90% for proximal vein. The shear-thinning blood viscosity model of Quemada was
used with a fluid density of 1054kg/m³. WSS was evaluated in a region of interest
at the venous anastomosis, being the region where clinical complication typically
occur. Special attention was paid to zones with WSS lower than 0.4Pa, a possible
threshold for intimal hyperplasia formation and atherosclerosis.
For the CG, an area of low WSS of 0.405cm² was found, while this was only
0.139cm² for the SG. Hence, the SG effectively reduces low WSS zones.
However, the statement that the SG solves problems of stenosis formation in
clinical practice, should be considered with care.
465
Int J Artif Organs 2010 ; 33 ( 7): 466
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P87 (242)
Clinical manifestations of coronary heart disease in end-
stage renal disease (hemodialysis)
M. Gashi, H. Korca, D. Kocinaj, E. Pllana, S. Rexhepi, F. Hasku
Internal Clinic, UCC of Kosova, Kosova
Objectives: Cardiovascular disease (CVD) is an important predictor of mortality
in patients with end-stage renal disease (ESRD) and accounts for almost 50%
of deaths. Very few studies have been performed in this group.
Methods: We examined coronary heart disease (CHD) and incidence of different
clinical manifestation during two years of follow-up period. In our group 125
patients with ESRD [men (44%) and women (56%)], aged 20-78 years (mean
age 56.4±13.9) were on hemodialysis.
Results: For two years of follow-up period in 125 patients on hemodialysis, the
most common clinical manifestation of CHD was angina pectoris with the typical
history of exercise-induced chest discomfort in 41 patients (33%). Hypotension,
in 20 patients (16%), was often present in patients with angina at the beginning
of hemodialysis. Chronic heart failure in 50 patients (40%), sudden cardiac arrest
in 5 patients (4%) and myocardial infarction in 7 patients with high mortality rate
(65%) were present. Different type of arrhythmias has been observed in up to
50% of dialysis patients during electrocardiogram analysis.
Conclusions: Patients with end-stage renal disease are more likely to present
with atypical symptoms of coronary heart disease, which may delay diagnosis
and adversely affect outcomes. CHD in our group of patients with ESRD
includes increased morbidity percentage. Mortality rate after an acute coronary
syndrome and myocardial infarction was high.
P88 (324)
BLOOD VESSEL DAMAGE MARKERS IN HEMODIALYSIS PATIENTS
P. Dejanov1, B. Dejanova2, G. Petrusevska3, G. Spasovski1, A. Sikole1
1
Clinic of Nephrology; 2Institute of Physiology; 3Institute of Pathology, Medical
Faculty, University “Ss. Cirilius and Methodius”, Skopje, R. Macedonia
Objectives: Vessel changes are common in hemodialysis (HD) patients. The aim
of this study was to examine the biochemical and pathohistological parameters
concerning blood vessels damage in HD patients.
Methods: A number of 50 HD patients were examined and compared to a
control group (n=30). The following biochemical parameters were determined:
triglycerides, LDL-ox antibodies, lipid peroxidation (MDA), and biological activity
of von Willebrand factor. The following methods were used: for triglycerides
(Merck, Germany), enzyme immunoassay for LDL-ox antibodies (Biomedica
gruppe, Austria), for MDA fluorimetric method with thiobarbituric acid; for von
Willebrand factor (vWf) combination assay by Dade Behring, Germany. For the
histopathological findings blood vessel sample was taken from a. radialis before
arterio-venous fistula creating.
Results: Increased levels of following parameters were found: for triglicerids,
2.90±1 mmol/L (p>0.05), for LDL-ox antibodies, 356 ± 259 mU/mL (p<0.01),
for lipid peroxidation, 5.40±01.0 µmol/L (p<0.01) and for biological activity of
vWf, 128% (p<0.05). Histopathological findings showed blood vessel changes
regarding intima and media with foam cells proliferation in smooth muscle cells.
Conclusions: From the obtained results, oxidative stress may be considered
due to increased level of MDA and LDL-ox antibodies. Furthermore, the
increased vWf biological activity and blood vessel changes may confirm the
certain endothelial dysfunction in HD patients.
Vascular and Biomaterials
P89 (36)
SALMON COLLAGEN TUBES WITH CIRCUMFERENTIAL COLLAGEN
FIBRIL ORIENTATION FOR SMALL CALIBER VASCULAR GRAFTS
Y. Nakayama1,2, M. Nakamichi1,3, M. Yamanami1,4, K. Takamizawa1, M. Munekata2,
K. Ihara5, K. Uchida3, K. Kanda4, H. Yaku4
1
Department of Bioengineering, Advanced Medical Engineering Center,
National Cardiovascular Center Research Institute, Osaka, Japan; 2Division
of Biotechnology and Macromolecular Chemistry, Graduate School of
Engineering, Hokkaido University, Sapporo, Japan; 3Department of Materials
Chemistry, Faculty of Science and Technology, Ryukoku University, Shiga,
Japan; 4Department of Cardiovascular Surgery, Kyoto Prefectural University
of Medicine, Kyoto, Japan; 5Ihara & Company Ltd., 3-263-23 Zenibako, Otaru,
Japan
466 © 2010 Wichtig Editore - ISSN 0391-3988
Objectives: Development of robust and elastic collagen tubes based on the
circumferential collagen fibril orientation as small caliber vascular grafts.
Methods and Results: Mixture of an acidic salmon collagen solution (0.2 w/v%)
and a fibrillogenesis-inducing buffer containing a crosslinking agent [water
soluble carbodiimide (WSC)] in a tubular mold, prepared by combination of an
external cylinder and a mandrel, were incubated at 4 degrees for 24 h for the
formation of tubular gels by simultaneous fibril formation and crosslinking, and
then the obtained gels after inserting rods in those inside were re-incubated
at 60 degrees for 5 min for shrinkage by thermal denature of collagen, finally
re-crosslinked in an ethanol solution containing WSC in the presence of rods
insertion. The dimension of the resulting tubular gels was easily controlled by
changing the size of the molds and rods used. The collagen fibril in the gels was
generally oriented at circumferential direction, due to that the shrinkage force
was limited in circumferential direction by insertion of the rods. The gels could
be elongated up to approximately 250%. The compliance was comparable with
those of native vessels. The elastic modulus of the gels was about 5 times larger
than that of gels prepared without rods.
Conclusions: Since the concentration of collagen in the gels was approximately
5 w/v% irrespective of using rods at shrinkage step, it was concluded that highly
robust and elastic modulus was induced by collagen fibril orientation.
P90 (103)
APPLICATION OF BIOTUBE VASCULAR GRAFTS TO ABDOMINAL REGION
IN A BEAGLE MODEL
T. Watanabe1,2, M. Yamanami1,2, K. Kanda1, H. Ishibashi-Ueda3, H. Yaku1,
Y. Nakayama2
1
Department of Cardiovascular Surgery, Kyoto Prefectural University of Medicine,
Kyoto, Japan; 2Department of Bioengineering, National Cardiovascular Research
Center, Osaka, Japan; 3Department of Pathology, National Cardiovascular
Research Center, Osaka, Japan
Objectives: From ESAO 2005 we have reported that in vivo tissue-engineered
autologous tubular tissues “BIOTUBEs” are useful as small-caliber vascular
grafts in rat or rabbit models. Their autologous connective tissue walls
(thickness: ca. 0.1mm) exhibited rapid vascular regeneration mechanically
and histologically, and induced neither immunological rejections nor
inflammatory reactions. In this study, BIOTUBEs were applied to large caliber
vascular grafts (over 5 mm) with the high blood pressure equivalent to that
of humans.
Methods: Y-shaped BIOTUBEs for common iliac grafts were prepared by
2-month placement of Y-branched silicone molds (diameter: 8 mm in main, 4
mm in branch) into dorsal subcutaneous pouches of beagle dogs (10 kg). The
straight BIOTUBEs for abdominal grafts were obtained in a similar manner by
using rod-shaped molds (diameter: 5 to 8 mm).
Results: After removing the molds from the implants harvested with around
connective tissue, Y-shaped or straight BIOTUBEs mostly consisting of collagen
fibers and fibroblasts were obtained. The BIOTUBEs were auto-implanted to
abdominal Aorta of Beagle dogs. After de-clamping pulsatile blood flow without
formation of aneurysms nor rupturing were observed. Angiography after
1-month implantation showed no formation of aneurysms nor stenosis. Further
study is ongoing to investigate morphological and physiological changes of the
implanted BIOTUBEs.
Conclusions: Large diameter BIOTUBEs formed in the Beagle dogs could apply
to the abdominal aorta of Beagle dogs. Large diameter BIOTUBEs indicated
their potentiality replacing the short-coming homografts for infectious or/and
inflammatory aneurysms.
P91 (51)
Histological Evaluation of Small-Caliber “BIOTUBE” Vascular
Grafts after Implantation in Rats
M. Yamanami1,2, H. Ishibashi-Ueda3, A. Yamamoto4, H. Iida4, T. Watanabe1,2,
K. Kanda1, H. Yaku1, Y. Nakayama2
1
Dpt of Cardiovascular Surgery, Kyoto Prefectural University of Medicine,
Kyoto, Japan; 2Dpt of Bioengineering, National Cardiovascular Center Research
Institute, Osaka, Japan; 3Dpt of Pathology, National Cardiovascular Center
Hospital, Osaka, Japan; 4Dpt of Investigative Radiology, National Cardiovascular
Center Research Institute, Osaka, Japan
Objectives: We are developing functional autologous tubular tissues, namely,
“BIOTUBEs”, as ideal small-caliber vascular grafts that have growth potential
without immunological rejection. In this study, BIOTUBEs were auto-implanted
in rats, and we evaluated histological changes of BIOTUBEs after implantation
to rat abdominal aorta.
Methods and Results: Silicone rods (diameter: 2 mm; length 20 mm) were
Int J Artif Organs 2010 ; 33 ( 7): 467
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
used as a mold for BIOTUBE preparation. The rods were placed into dorsal
subcutaneous pouches in rats. After 4 weeks, the implants were removed.
BIOTUBEs were obtained from the implants after pulling out the rods. BIOTUBE
vascular grafts after nonthrombogenic drug coating were implanted into
abdominal aorta of rats by end-to-end anastomosis using a custom-designed
sutureless vascular connecting system under microscopic guidance (n = 6).
Graft status was evaluated by contrast free time-of-flight magnetic resonance
angiography (TOF-MRA). BIOTUBEs were harvested after 12 week- implantation
and evaluated histological changes. The patency rate was 66.7% (4/6) at 12
weeks after implantation. MRA showed little stenosis and no aneurismal dilation
of BIOTUBE grafts. The wall thickness at the middle portion of BIOTUBE
was increased from about 70 μm (before implantation) to about 200 μm (after
implantation). Histological examination of implanted BIOTUBEs showed that
the luminal surface was completely covered by endothelial cells and neointima,
including an elastin fiber network and circumferential orientation of collagen
fiber and smooth muscle cells.
Conclusions: BIOTUBEs could be used as small-caliber vascular prostheses
that greatly facilitate healing process and exhibit excellent biocompatibility.
P92 (101)
IMPROVING HEMOCOMPATIBILITY OF A NEW GENERATION OF
NANOCOMPOSITE POLYMER FOR CARDIOVASCULAR APPLICATION BY
PLASMA TREATMENT
S. Atefeh1, S.H. Mehran1, N. Siamak1, M. Hamid1,2, M.S. Alexander3,4
1
Biomedical Engineering Faculty, Amirkabir University of Technology, Tehran,
Iran; 2Iran Polymer and Petrochemical Institute (IPPI), Tehran, Iran; 3Center
for Nanotechnology & Regenerative Medicine, UCL Division of Surgical &
Interventional Sciences, University College London, London, UK; 4Royal Free
Hospital Hampstead NHS Trust, London, UK
Objectives: We have developed and patented a novel nanocomposite polymer
for biomedical application, the material based on polyhedral oligomeric
silsesquioxane (POSS) nanoparticle and poly(carbonate urea)urethane (PCU)
polymer. The polymer has in vitro and three years large animal study in vivo
and currently undergoing CE Mark. To enhance the in situ endothelization of
graft, we applied various techniques. Out of various techniques, plasma surface
modification has been proven to be effective. Therefore, we studied oxygen
plasma treatment effect on the hemocompatibility of POSS-PCU.
Methods: POSS-PCU was synthesized and film was manufactured. Films were
treated with 60 W of oxygen plasma for 30 and 120 sec. Untreated film was
used as control. Hemolysis ratio: The samples were contacted with whole blood
and kept at 37 °C for 60 min. Then the supernatant was measured at 540 nm to
determine the absorbency of cells undergoing hemolysis. HR is calculated as
follows: HR= (A-C1)/(C2 –C1) x 100%, A: the absorbance of sample supernatant
C1: absorbency of the negative controls, C2: absorbency of the positive control.
Platelet adhesion: all samples were contacted with Platelet-rich plasma (PRP)
at 37 °C for 1 h. After incubation, films were removed from the tubes and the
remaining platelets counted. PA was calculated as follows: PA = 100 x [(C – T) /
C], where C is the reference count and T is the test count.
Results: The percentage of PA and HR of treated POSS-PCU in comparison
with untreated one exhibits significant reduction (P value less than 0.05).
Conclusions: These findings suggest that plasma treatment of POSS-PCU
could be an attractive way to improve Hemocompatibility and endothelization
of graft. Outcome will be higher patency rate of small-diameter vascular grafts.
P93 (236)
(BIO) DEGRADABLE POLYURETHANES FOR ELECTROSPUN VASCULAR
GRAFTS
S. Baudis1, C. Grasl2,4, H. Bergmeister3,4, M. Arras2, B. Winter5, H. Schima2,4,5,
R. Liska1
1
Vienna University of Technology, Institute of Applied Synthetic Chemistry,
Vienna, Austria; 2Medical University, Center for Med. Physics and Biomed.
Eng., Vienna, Austria; 3Medical University, Core Unit for Biomed. Research,
Vienna, Austria; 4LBC for Cardiovasc. Res., Vienna, Austria; 5Medical University,
Department of Surgery, Vienna, Austria
Objectives: Electrospinning is a very powerful method to create fibrous scaffolds
for artificial vascular grafts. Commercially available TPUs, like Pellethane™ (Dow
plastics) have already shown excellent biomechanical properties as electrospun
vascular grafts. In order to induce the growth of a neo-artery and hence increase
the long-term patency of the graft the use of biodegradable TPUs is beneficial.
Therefore we aim for the development of degradable TPUs.
Methods: As the TPU polymer backbone consists out of 2 moieties – the hard-
and the soft-blocks – it is possible to introduce degradability at both sites. The
© 2010 Wichtig Editore - ISSN 0391-3988
application of cleavable chain extenders (CCE) leads to hard-block degradable
TPUs. Therefore we synthesized a number of TPUs consisting of different lactid-
and ethylene glycol-based CCE and examined their mechanical performance
and degradability. The expected degradation products were synthesized and
tested for their cytotoxicity with an EZ4U test.
Results: The mechanical tensile strength of the electrospun synthesized TPU
is dependent on the kind and ratio of the applied CCE with maximal rate 20%
higher than Pellethane™. The degradation tests were conducted at elevated
temperatures to accelerate the process. Surgical PLA was used as reference.
The TPUs with different chain extenders degraded with 10 to 200% of the rate
of PLA. The expected degradation products showed no cytotoxicity under
in vitro test conditions up to a concentration of 1 mmol/L.
Conclusion: With our electrospinning method the degradable polyurethane
grafts can be produced with a grade of quality comparable to the established
Pellethane™ prostheses. The influence of the degradation on the mechanical
tensile strength has to be investigated in further tests.
P94 (137)
MECHANICAL PROPERTIES OF HYDROXYAPATITE-TANTALUM
COMPOSITES
M. Yetmez1, N. Demirkol2,3, F.N. Oktar4,5, O. Gunduz6,7,5, S. Kayali3,
S. Agathopoulos8
1
Mech. Eng. Dept., Karaelmas Univ., Zonguldak, Turkey; 2Tech. Prog. Dept.,
Vocational School of Degirmendere Ali Ozbay, Kocaeli Univ., Golcuk, Turkey;
3
Metall. & Mater. Sci. Dept., Istanbul Tech. Univ., Istanbul, Turkey; 4Medical
Imaging Tech. Dept., Marmara Univ., Istanbul, Turkey; 5Nanotech. Biomater.
Application & Res. Centre, Marmara Univ., Istanbul, Turkey; 6Mech. Eng. Dept.,
Univ. London College, UK; 7Metal Edu. Dept., Marmara Univ., Istanbul, Turkey;
8
Mater. Sci. & Eng. Dept., Ioannina Univ., Ioannina, Greece
Objectives: Hydroxyapatite (HA) is one of the most widely used biomaterials
for reconstruction of the skeleton. HA is nontoxic and biocompatible with bony
tissues. It is used as implant material both in bulk form and thin coatings on
metals. Nevertheless, bulk HA materials are very fragile. Therefore, it is often
reinforced with a secondary phase. In this study, Ta was selected to be the
reinforcing phase of HA because it is a well-known biocompatible material for
coatings and there are no studies on HA-Ta composites in the literature. The aim
of this study is to produce HA-composite materials with improved mechanical
and bio-properties.
Methods: HA was produced from bovine bones (BHA). BHA was mixed with
0.50 – 1%wt Ta. Green compacts were sintered between 1000 and 1200°C.
Measurements of compression strength and Vickers microhardness along with
SEM observations and X-ray diffraction analysis were carried out.
Results: X-ray diffraction analysis identified HA, fluorapatite (FA) and Ta-
associated phases. The best compression strength was achieved as 71.13Mpa
for 0.25 wt% Ta sintered at 1200°C. The highest microhardness was 363 HV for
1200°C sintering temperature and 0.50 wt% Ta.
Conclusions: BHA-Ta composites can be regarded as a good bone substitute
for partially load bearing areas in orthopedic applications. Further developments
of increasing mechanical and bio-properties are in progress.
P95 (136)
A NEW SAFE METHOD TO PRODUCE BIOCERAMIC NANO-POWDERS
FROM NACRE VENUS VERRUCOSA
F.N. Oktar1,2, U. Tuyel3, N. Demirkol4,5, O. Gunduz6,7,2, R. Samur7, S. Kannan8,
S. Agathopoulos9
1
Medical Imaging Tech. Dept., Marmara Univ., Turkey; 2Nanotech. Biomater.
Application & Res. Centre, Marmara Univ., Turkey; 3Mech. Eng. Dept., Aveiro
Univ., Aveiro, Portugal; 4Tech. Prog. Dept., Voc. School of Degirmendere
Ali Ozbay, Kocaeli Univ., Turkey; 5Metall. & Mater. Sci. Dept., Istanbul Tech.
Univ.,Turkey; 6Mech. Eng. Dept., Univ. London College, UK; 7Metal Edu. Dept.,
Marmara Univ., Turkey; 8Ceram. & Glass Eng. Dept., Aveiro Univ., Aveiro
Portugal; 9Mater. Sci. & Eng. Dept., Ioannina Univ., Greece
Objectives: Hydroxyapatite (HA) nano-powders, currently one of the most
demanding challenges for producing new biomaterials, have been produced
only when starting from chemical reagents. Hydrothermal transformation,
where pure aragonite from nacres, shells and corals transforms into HA at very
high pressures, is a dangerous technique if the equipment is worn. This work
presents a safe, efficient and economic way to produce HA nano-powders via
ultrasonic and hotplate method from Venus Verrucosa nacres.
Methods: Aqueous suspension of powders from crushed and milled nacres
was put on a hotplate that was ultrasonically agitated. The temperature was set
at 80°C for 15 min. Then, chemically equivalent amount of H3PO4 was added,
467
Int J Artif Organs 2010 ; 33 ( 7): 468
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
drop by drop, into the suspension. The reaction lasted for 8-24 hours. Then,
the liquid evaporated and the resultant mixture was put into an incubator at
100°C for 24 hours. The powders were calcinated between 450-850°C for 4
hours in air.
Results: X-ray diffraction analysis identified phases of HA, FA, α-TCP, β-TCP
and CaO. Nano-bioceramic particles sized between 280 and 540 nm were
observed after 24 hours cycles of treatments.
Conclusions: The high availability and the low cost of all kind of nacre shells,
along with their biological-natural origin, are attractive features conferring them a
high potential for preparing nano-powders of HA for uses in biomedicine. Venus
Verrucosa can be ideal candidate for producing nano-bioceramic particles.
Acknowledgements: This study was supported by FEN-B-250608-0180 multi
discipline research project from BAPKO, Marmara Univ. Sci. Res. Committee.
P96 (156)
NANOCRYSTALLINE Mg, Ca HYDROXYAPATITE AND THE STABILITY OF
ALGINATE COATINGS
E.A. Krylova1, S.E. Krylov1, L.I. Demina2, M.E. Krasheninnikov3
1
OOO “ZIMTEC”, Russia; 2Federal V. Shumakov Research Center of
Transplantology and Artificial Organs, Russia; 3Kurnakov Institute of General
and Inorganic Chemistry RAS, Russia
Objectives: The influence of Mg on Ca hydroxyapatite (HA) crystallization and
the interactions of the Mg with HA by FTIR, SEM, XRD, EPR and elemental
analysis are studied. Moreover, process for forming porous alginate matrix (ALG)
in system CaCl2-Mg,Ca HA is studied and optimized. The porous ALG coatings
produced by gelation technique were studied so as to provide the stability in
blood at storage. The possibility of cells immobilization is considered.
Materials and Methods: Phase-reinforcement of Ca HA was achieved by
addition of MgSO4 (5-30wt.%) in HA powder and subsequent sintered at 900°C
for 1 h. ALG (Sigma) coatings were formed in CaCl2-Mg,Ca HA suspension
using plastic forms and then successively transferred into PBD solution and
blood.
Results: The X-ray diffraction pattern of the Mg, Ca HA did not indicate any
decomposition of HA structure. Analysis of the powder by different physical
methods allows to conclude that hydroxyapatite structure is kept and the presence
of Mg affects the crystallization yielding nano-scale powder. The experiments
indicate that formation of ALG matrix in CaCl2-Mg, Ca HA suspension in narrow
interval of concentrations accompanied by the precipitation of white powder
on the surface of ALG coatings. The technique allows receiving ALG structure
with optimal pore size (100-400 microns) providing stability of coatings in PBS
and blood.
Conclusions: Stable ALG coatings as biomaterial for immobilization of cells for
use in transplantation are proposed. Effect of stability ALG coatings seems to
be related to the presence of Mg in the HA structure.
P97 (335)
FABRICATION OF NEW BONE CEMENT WITH TITANIUM MODIFIED
HYDROXYAPATITE AND CALCIUM SULFATE
A. Slósarczyk, A. Zima, Z. Paszkiewicz, J. Szczepaniak
AGH, University of Science and Technology, Cracow, Poland
The use of calcium sulfate as a bone defect filler has a long clinical history and this
material has been demonstrated as biocompatible and quickly biodegradable.
Calcium phosphate-based bioceramics, including hydroxyapatite (HA) have
been proved to have excellent bioactive properties and are very popular to
use as a bone substitute. Results of previous studies showed that bioactive
potential of titanium modified hydroxyapatite ceramics is higher than that of
pure HA. Calcium phosphate cements due to their unique properties (bioactivity,
injectability and in vivo setting ability) are a family of very promising materials in
bone regeneration.
In this study, calcium sulfate hemihydrate (CSH) was combined with titanium-
doped hydroxyapatite (TiHA) to develop a novel bone cement. TiHA was
obtained by a wet method. Three compositions with different CSH:TiHA weight
ratios, namely 3:2, 2:3 and 1:4 were examined. Pure CSH (Acros Organics)
was used as a reference. Distilled water and Na2HPO4 solutions (1.25% and
2.5%) were applied as liquid phases. The self–setting cement samples were
prepared by mixing powder batches with liquid phases at the given L/P ratios
for achieving appropriate rheological properties of a paste.
Initial (I) and final (F) setting times of the cements were determined with Gillmore
apparatus and differed in the range of 2-15.5 min (I) and 4-75 min (F). Increase
in the amount of CSH in composition resulted in decreasing required L/P ratio
as well as in shorter setting time. When the amount of TiHA exceeds 80 wt%,
too long setting time of cement makes it unacceptable as a bone filler. The
468 © 2010 Wichtig Editore - ISSN 0391-3988
phase composition of the hardened cement bodies was characterized by XRD
method and microstructure of fractured surfaces by SEM. Porosity of the final
samples was evaluated by Hg porosimetry. The results obtained suggest that
CSH-TiHA cements have the potential to be applied in bone substitution and
for delivery of drugs.
Acknowledgements: This work has been supported by the project No WND-
POIG.01.03.01-00- 005/09.
P98 (135)
MECHANICAL PROPERTIES OF BOVINE ENAMEL DERIVED
HYDROXYAPATITE
N. Demirkol1,2, M. Yetmez3, U. Karacayli4, E.S. Kayali2, O. Gunduz5,6,7,
S. Agathopoulos8, F.N. Oktar9,7
1
Tech. Prog. Dept., Vocational School of Degirmendere Ali Ozbay, Kocaeli Univ.,
Golcuk, Turkey; 2Metall. & Mater. Sci. Dept., Istanbul Tech. Univ., Istanbul,
Turkey; 3Mech. Eng. Dept., Karaelmas Univ., Zonguldak, Turkey; 4Oral Maxillo-
Facial Dept., Gulhane Military Med. Academy, Ankara, Turkey; 5Mech. Eng.
Dept., Univ. London College, London, UK; 6Metal Edu. Dept., Marmara Univ.,
Istanbul, Turkey; 7Nanotech. Biomater. Application & Res. Centre, Marmara
Univ., Istanbul, Turkey; 8Mater. Sci. & Eng. Dept., Ioannina Univ., Greece;
9
Medical Imaging Tech. Dept., Marmara Univ., Istanbul, Turkey
Objectives: Hydroxyapatite (HA), the main mineral component of bones and
teeth, is among the leading biomaterials. Nevertheless, materials of pure HA
feature low mechanical strength and fracture toughness, which limit their use
in load-bearing applications. The HA bioceramics can be synthetic or natural.
The former ones are reliable but their production is usually complicate and
expensive. Natural HA production is regarded as an economic process. The aim
of this study is to produce naturally derived HA materials for grafting purposes.
Methods: Natural HA powder was obtained from calcinated bovine tooth enamel.
Powder-compacts were sintered between 1000 and 1200°C. Compression
strength and Vickers microhardness were measured. SEM and X-ray diffraction
studies were also conducted.
Results: X-ray diffraction analysis identified HA and fluorapatite associated
phases. The highest compression strength was achieved as 37.25Mpa after
sintering at 1100°C. A similar recent study has shown compression strength for
human enamel HA sintered at 1100°C 38.81Mpa. The highest microhardness
was measured as 132.5 HV for 1200°C sintering temperature.
Conclusions: Bovine enamel HA can be regarded as a good bone substitute
but only for non-load bearing areas in orthopedic surgery. Further developments
of increasing mechanical properties are in progress.
Acknowledgements: This study was supported from FEN-DKR-140607-0122
(Improving of HA coatings on biomedical implants and efficiency analysis) from
BAPKO, Marmara Univ. Sci. Research Committee.
P99 (253)
EVALUATION OF MAGNESIUM ALLOYS AS DEGRADABLE IMPLANT
MATERIAL
F. Evertz2, B. Glasmacher2, M. Kietzmann3, P.P. Mueller1, H. Hauser1
1
Helmholtz Centre for Infection Research, Braunschweig, Germany; 2Institute for
Multiphase Processes, Hannover, Germany; 3University of Veterinary Medicine
Hannover, Hannover, Germany
Tissue compatible degradable implant materials aim to avoid repeated surgery
in cases where the implant function is only transiently needed. Intensive
research is carried out on degradable metallic implants and clinical trials have
been started. Currently available results indicate that metallic alloys are often
superior over other materials and have additional specific advantages. In
particular, magnesium implants are able to enhance regeneration processes in
the bone. Further, due to its superior mechanical properties magnesium alloys
can be used in the cardio-vascular area as coronary stents. New dates indicate
a low tendency to induce inflammation and mild anti-bacterial effects by
magnesium alloys. However, there is room for improvements before magnesium
alloys can be routinely used in the clinics. These concern a high degradation
rate connected with hydrogen production and limited tissue damage. New
methods for the analysis and evaluation of magnesium alloys were established
and tested. Degradation in vivo is significantly slower as compared to in vitro
within technical corrosion tests. In vivo, Mg(OH)2 as well Ca and phosphate
were detected at the implant site where Ca and phosphate clearly correlate with
bone remodelling. A mouse model is used to understand the bone regeneration
process induced by the implant. An ex vivo bovine udder model will be used
to study degradation product allocation, reactions of inflammation and the
degradation kinetics. With a dynamic in vitro test system the degradation
process will be studied with regard to the type of corrosion, its products and its
Int J Artif Organs 2010 ; 33 ( 7): 469
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
kinetics. This study will use different implant geometries and model fluids for the
dynamic degradation tests.
Acknowledgements: This project is funded by the German Research Foundation
within SFB 599 – Sustainable bioresorbable and permanent implants of metallic
and ceramic material.
Cardiovascular device engineering
P100 (263)
Pediatric Intraaortic Balloon Pumping for Left Ventricular
Assistance
G. Pantalos, M. K. Sharp
University of Louisville, USA
Intraaortic balloon pump (IABP) therapy has been used extensively for the
treatment of left ventricular failure in adult patients for decades. The use of the
IABP in pediatric patients, particularly infants and small children, is commonly
thought to be ineffective due to the elevated heart rates, difficulty with catheter
insertion, and greater compliance of the pediatric aorta. Laboratory and clinical
research have developed methods to make IABP therapy in pediatric patients
effective.
The elevated heart rates associated with pediatric patients can make triggering
IABP inflation challenging. The small, pediatric IABP catheters cannot
accommodate a fluid filled lumen for arterial pressure monitoring (like adult
IABP catheters) making the determination of inflation and deflation timing
landmarks difficult especially when using radial artery pressure monitoring
that can introduce delays and distortions of the landmarks. Animal and clinical
studies have shown that the use of high fidelity monitoring of the aortic pressure
waveform or echocardiographic imaging of aortic valve opening and closing
greatly improves the identification of IABP inflation and deflation landmarks
and leads to improved outcomes in pediatric patients supported by the IABP.
Using the echocardiographic imaging approach, one center has improved
pediatric IABP patient survival from 35% to 62%. One clinical study of aortic
input impedance in pediatric patients has also indicated that contrary to
the prevailing dogma, the pediatric aorta is actually less compliant than the
adult aorta, meaning that correctly timed counterpulsation with the IABP can
be effective. Animal investigations have demonstrated that it is possible to
successfully trigger IABP inflation up to 220 beats per minute. The absence of
a percutaneously inserted version of the pediatric IABP catheter has lead to the
development of techniques to successfully introduce the catheter into peripheral
arteries. The combination of these findings suggests that correctly used IABP
counterpulsation therapy for pediatric patients in left ventricular failure may be
effective and is a viable option for clinicians to consider.
P101 (71)
STUDY OF TOTAL ARTIFICIAL HEART COMPOSED OF AXIAL FLOW
PUMPS AND ITS HEMOLYSIS CHARACTERISTIC
Li Guo Rong, Zhu Xiao Dong
Department of Cardiac Surgery, Fu Wai Heart Hospital & Cardiovascular Institute,
Peking Union Medical College & Chinese Academy of Medical Sciences Peking,
China
Objectives: A total artificial heart (TAH) composed of two axial flow pumps was
developed and evaluation studies are underway.
Methods: Currently the prototype TAH was columniform with a diameter of
57mm and a length of 67mm. The rotary speed (RS) of right pump (RP) and left
pump (LP) could be separately adjusted to create proper output for pulmonary
and systemic circulation respectively. The TAH can yield a flow rate of 5l/min at
30 mmHg pressure and 7900 rpm for (RP) or at 100 mmHg pressure and 10100
rpm for LP. Pulsant output could be produced by control of the electricity supply
to the TAH in a simply discontinuous fashion. With the fluctuation rate of 60
beats per minute, the systolic pressure of 120 mmHg would be generated by
increasing RS to 11880rpm for LP and systolic pressure of 42mmHg to 8600rpm
for RP. Under the same mean output (pressure and FR) the blood damage of the
prototype TAH was compared between the two control fashions.
Results: The normalized hemolysis index (NIH) was 0.045g/100L for continuous
output fashion and 0.063g/100L for pulsant output fashion.
Conclusions: Total artificial heart (TAH) composed of axial flow pumps was feasible
but fluctuation in output would induce more hemolysis, implying that a TAH of
continuous output should be used if it was proved to be physiologically accepted.
© 2010 Wichtig Editore - ISSN 0391-3988
P102 (87)
COMPLETELY IMPLANTABLE BIVENTRICULAR ASSIST DEVICE FOR
DESTINATION THERAPY
A. Wimmer1, T. Schmid1, B. Vodermayer1, H. Gmeiner1, W. Schiller2, K. Lehle3,
C. Schmid3, A. Welz2, G. Hirzinger1
1
Institute of Robotic Systems, German Aerospace Centre DLR, Germany; 2Clinic
for Heart Surgery, Univ. of Bonn, Germany; 3Department of Cardiothoracic
Surgery, Univ. Medical Centre Regensburg, Germany
Objectives: Right heart failure is a common complication in patients with LVAD
therapy. To assist both ventricles with one device, a completely implantable,
pulsatile BVAD with specific assistance for the left and right heart is to be
developed.
Methods: The compact device includes two pump chambers that are alternately
compressed by hydraulic fluid, using a high efficient electro-hydraulic energy
converter. Hydraulic bearings enable enhanced lifetime of the gear. The flat
design (Vol. 410cc) allows for complete implantation. Differentiated ejection and
acute control of the stroke volume is enabled by a control algorithm, monitoring
the filling of the pump chambers and the heart frequency. New seamless pump
chambers are optimized by CFX and flow measurements using non-Newtonian
fluid. The surfaces of the pump chambers are textured to allow cell adhesion.
The TET is verified in vitro, enabling complete implantation without the need of
drivelines.
Results: The performance and durability of the BVAD was tested in mock loops
up to 65 days. With a frequency of 130bpm, the BVAD generates 5.2 l/min output
for each ventricle. A speed of 6400 rpm of the drive unit enables the maximum
pump frequency of 180 bpm with a maximum flow of 7.2 l/min. The energy
consumption of the pump is between 6 and 11 Watt. A nearly physiological flow
field is generated in the new chambers. During filling phase, two recirculation
zones similar to those found in the human left ventricle are observed. Increased
shear rates up to 1500 1/s are observed downstream the inflow. No superior
warming of the drive unit was measured.
Conclusions: The developed BVAD combines the advantages of displacement
pumps and rotary blood pumps to support patients up to a BMA of 1.8 m2.
Separate control of the stroke volume and triggering the BVAD’s frequency to
the heart should enable sufficient unload of the ventricles.
P103 (80)
INFLUENCE OF HEART VALVE DIMENSIONS ON THE EFFICIENCY OF
PULSATILE BLOOD PUMPS
T. Schmid1, M. Stock2, W. Schiller3, D. Liepsch2, A. Welz3, G. Hirzinger1
1
Institute of Robotic Systems, German Aerospace Centre; 2Institute of
Aerodynamics, Technical University of Munich, Germany; 3Clinic for Heart
Surgery, University of Bonn, Germany
Objectives: The efficiency of pulsatile blood pumps is limited due to the
resistance of the valves, causing improper forming of vortex during the filling
phase. The goal is to develop a characteristic number, specifying an expedient
size of heart valve fitting the given volume of a pump chamber or heart
ventricle.
Methods: To verify the influence of the valve, flow visualisation with birifringent
fluid and flow measurements with Particle Image Velocimetry and a bloodlike
non-Newtonian model fluid were carried out. Two different types of chambers
(bended and ventricle shaped) and three different sizes of heart valves were
investigated. The chambers were compressed with a rigid pusher plate and
with a hydraulic fluid in a second experiment. 3D-shear stress, vorticity and
3D-pathlines were calculated (spatial resolution 1.3mm).
Results: A profoundly influence of the heart valve’s diameter on vortex forming
is observed. To characterize the loss of hydraulic efficiency caused by the
valve, a dimensionless characteristic number “Ze” is defined as a ratio between
valve diameter, chamber volume, vorticity and frequency. A significant, inverse
proportional coherence between Ze and the hydraulic efficiency is documented.
Using a 21mm valve causes high vorticity with Ze=16.8 and low hydraulic efficiency
(30%) where a 23mm valve reduces secondary flow phenomena (Ze=2.1) and
increases the hydraulic effiency (46%). Ze = 7 indicates a critical point for proper
filling and wash out, higher values lead to a rapid decrease of efficiency.
Conclusions: A strong influence of heart valve functionality and dimension was
documented in several studies in the past. The defined dimensionless number
Ze is a reliable base for estimating the required valve dimension when scaling
a pulsatile pump. It has to be investigated if Ze is more relevant in the clinical
setup of valve replacement than the prosthesis-patient-mismatch approach.
469
Int J Artif Organs 2010 ; 33 ( 7): 470
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P104 (82)
THE STAGES OF DEVELOPMENT AND RESEARCH OF AN IMPLANTABLE
AXIAL-FLOW ASSIST DEVICE: VISH PUMP
G.P. Itkin1, D.V. Vashurkin1, A.M. Nevzorov1, S.V. Selishev2, E.G. Konysheva1,
G.S. Kuzmin2, V.A. Malgichev2, M.U. Shagidulin1, S.V. Gautier1
1
Federal V Shumakov Research Centre of Transplantology and Artificial Organs,
Moscow, Russia; 2Moscow Institute of Electoronic Technology (Technical
University), Moscow, Russia
Objectives: To develop and study the implantable axial pump for assisted
circulatation.
Methods: In the process of designing the implantable axial pump the geometry
of its basic elements (straightener, impeller, diffuser) were calculated on a
computer model using CFD-methods. On the principle of minimizing the stress,
zones of stagnation and recirculation the parameters of main elements were
optimized. The design of the pump was developed with integrated DC motor
and bearing units into the bloodstream. The bearings are the most critical parts
of the pump because the design of the bearings defines a resource of the pump
and its reliability, including probability of thrombus formation. Past tribological
studies of various materials have shown promise for the use a diamond-like
coating on the materials of high hardness with a well-surfaced. Testing of these
materials on the adhesion of platelets showed that the diamond-like coating has
high biocompatibility properties comparable with heparin coatings.
Results: The in vitro testing of prototypes were conducted on the mock
circulation, with measuring the flow rate at a fixed pressure differential of the
pump and different rotor speed. The report will include flow rate - pressure
and power characteristics of the pump on the mock circulation with the water-
glycerol (35%) mixture and blood. The pump provided flow rate of 5 l/min at a
differential pressure of 100 mmHg on the rotor speed (8000 rpm) with power
requirement of 7 watts.
Conclusions: This work showed the possibility of transition to the next phase of
the study of the pump in experimental animals.
P105 (195)
Development of a new centrifugal LVAD system: Heart
Turcica Centrifugal
O. Demir1 E. Biyikli1 I. Lazoglu1 S. Kucukaksu2
1
Manufacturing and Automation Research Center, Mechanical Engineering
Department, Koc University, Istanbul, Turkey; 2Department of Cardiovascular
Surgery, Yeditepe University Hospital, Istanbul, Turkey
A prototype of a new implantable centrifugal blood pump was developed as
a left ventricular assist device for the treatment of end-stage cardiac failures.
In the development of Heart Turcica Centrifugal, effects of blade height and
volute tongue profiles on the hydraulic and hemolytic performances of the
pump were investigated. The prototype was manufactured using the best blade
height and volute tongue profiles investigated. Performance of the prototype
model was experimentally measured in a closed-loop flow system using water
as the medium. The hydraulic performance requirement of a left ventricular
assist device (5 l/min flow rate against a pressure difference of 100 mmHg)
was attained at 2800 rpm rotational speed. In addition, two types of turbulence
models (k-? and k-?) used in computational fluid dynamics analyses were
compared to experimental results, but no major difference was observed.
P106 (128)
DEVELOPMENT OF A MINIATURE VENTRICULAR ASSIST DEVICE WITH
HELICAL FLOW PUMP FOR PEDIATRIC CASES
A. Baba1,2, K. Ohashi1, T. Isoyama2, Y. Inoue2, T. Ono2, I. Saito2, Y. Abe2
1
Shibaura Institute of Technology, Saitama, Japan; 2The University of Tokyo,
Tokyo, Japan
Objectives: In these days, heart transplantation is becoming more and more
difficult because of the shortage of hearts. Especially, the shortage of child
hearts is severe. In this study, a miniature ventricular assist device for these
children who are suffering from chronic heart failure and are heart transplant
candidates, is developed. Secondly, the performance of the device shall be
estimated with mock circuits.
Methods: In centrifugal pumps, the inlet and the outlet are behind and in front
of the axis. In axial-flow pumps, the inlet is opened in the vertical direction and
the outlet is on the surrounding side. So, when we use these type pumps, it is
necessary to use a long piping and the structure of devices becomes complex
shape, and the capacity needed for the burial grows. Therefore, the rotary
pump is hoped, which is small, its durability is high, and the inlet and the outlet
are both opened in the proximity on the surrounding side of the pump. So,
470 © 2010 Wichtig Editore - ISSN 0391-3988
we designed the helical flow pump, of shape with the inlet and outlet in the
same direction and in the next. Parts were produced by cutting the acrylic
plastic and the stainless steel. The outside diameter of the pump is 42mm. And
the diameter of the section of stream duct 6mm. There are 12 impellers. The
aimed performance of the pump is a size that could be buried in the body of
10kg in weight and 75cm in height. And, as for flow-rate, it is 2 l/min against
the maximum blood pressure 100mmHg. The performance of the pump was
evaluated with the mock circuits.
Results: The aimed values were not achieved. However, flow-rate was 2L/min
against the pressure of 49mmHg. It is thought that the aimed value can be
achieved if the pump can be turned by the rotational speed of 3000 rpm or
more. Moreover, it is thought that efficiency can be raised if the rotational speed
can be raised.
Conclusions: We plan to raise the rotational speed of the pump by adjusting
the part of the axis and the design and the production of the duct in the future,
and to make a more efficient.
P107 (152)
INVESTIGATION OF THROMBOGENESIS AND HEMOLYSIS IN THE POLISH
PEDIATRIC VENTRICULAR ASSIST DEVICE
M. Gawlikowski, K. Gorka, A. Kapis, R. Kustosz, W. Bujok
Foundation of Cardiac Surgery Development, Artificial Heart Laboratory, Zabrze,
Poland
Objectives: The subject of the investigation was hemolysis detection and
thrombus formation in a prototype of pediatric extracorporeal VAD. Heparinized
blood circulated in a mock circulatory system. During the experiment ACT
decreased from level of 4 times to 1.5 times of normal value (among 70-150s),
at this point the test was finished and the blood pump underwent inspection
regarding thrombus identification.
Methods: The in vitro circulation system was composed of the following
elements: blood pump, control unit, blood reservoir, water bath, pressure
sensor, flowmeter, drains, connection elements. Porcine blood circulated in
the system by a pressure of 90 mmHg, flow of 4.1 l/min and temperature of
37°C. Heparization in the blood bag increased ACT. During the experiment
heparin underwent dissolution and ACT decreased. The test was terminated
when ACT decreased to a level approximately 1.5 times of normal value. After
test termination, the blood pump underwent an inspection, thrombus formation
was investigated and documented photographically. As a reference a blood
bag filled with heparinized porcine blood was selected. Blood samples from the
circuit and the blood bag where obtained in the same time periods, to determine
ACT and hemolysis.
Results: During the experiment ACT decreased from 437 to 202 s and hemolysis
increased from 0.1 to 0.5 g/L. In the reference blood bag ACT decreased from
340 to 293 s, and the hemolysis increased from 0.2 to 0.3 g/L. Pump inspection
revealed thrombus in form of thin, white threads localized on the mechanical
valves and a thin red thread inside the pump.
Conclusions: The pump interior has a low thrombogenicity potential. Mechanical
valves utilized in the prototype generate thrombi, which correspond to those
developed in vivo. An increased hemolysis level was observed, the cause must
be investigated.
P108 (132)
DEVELOPMENT AND IMPROVEMENT OF THE RIGHT VENTRICULAR ASSIST
DEVICE USING AN ARTIFICIAL MYOCARDIUM WITH SHAPE MEMORY
ALLOY FIBERS - ESPECIALLY FOR THERMAL CHARACTERISTICS
A. Baba1,4, S. Hosoda1, R. Sakata2, Y. Sato2, M. Umezu2, D. Homma3, T.K. Sugai4,
H. Liu4, T. Yambe4, Y. Shiraishi4
1
Shibaura Institute of Technology, Saitama, Japan; 2Waseda University, Tokyo,
Japan; 3Toki Corporation, Tokyo, Japan; 4Tohoku University, Sendai, Japan
Objectives: We have been developing a mechano-electric artificial myocardial
assist system (artificial myocardium) for the right ventricle which is capable of
supporting natural contractile function from the outside of the right ventricle. In this
study, we particularly examined the temperature rise of shape memory alloy fibers.
Materials and Methods: The BioMetal Helix is a helical coil spring using a
shape memory alloy fiber made from Ni-Ti alloy with a diameter of 100 micron,
developed by the Toki Corporation. An artificial myocardium was made of the
BioMetal Helix and is activated by an electric current. The hydrodynamic and
hemodynamic functions of the artificial myocardium were examined in a mock
circulatory system as well as in animal experiments using goats. We measured
the temperature rise on the surface of the artificial myocardium, both in the
natural convection and on the ventricular surface, by the radiation calorimeter
and thermocouples.
Int J Artif Organs 2010 ; 33 ( 7): 471
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
Results: The temperature rise was to over 42° centigrade in the natural convection,
but it was not observed on the ventricular surface in animal experiments.
Conclusions: Experimental results show the temperature rise of the artificial
myocardium in the chest is not considered to be a problem. The artificial
myocardium may be potentially useful as a cardiac assist device. The pulmonary
high blood pressure has been observed by the long-term use of the traditional
right ventricular assist devices. But, the artificial myocardium may overcome the
problem and may be useful as a right ventricular assist device for the patients
suffering from right heart failure, such as patients in congenital heart disease
many years after surgical correction.
P109 (154)
POLISH EXTRACORPORAL VENTRICULAR ASSIST DEVICE FLOW
CONDITION - NUMERICAL ANALYSES AND PULSED ULTRASONIC
DOPPLER VELOCIMETRY
D. Jurkojc1, Z. Malota2, A. Kapis1, I. Altyntsev1, W. Bujok1, R. Kustosz1
1
Artificial Heart Laboratory; 2Biocybernetics Laboratory, Foundation for Cardiac
Surgery Development, Zabrze, Poland
Objectives: The aim of this work was the flow analysis performed with the
usage of computer fluid dynamics (CFD) analyses verified with hydrodynamic
fluid dynamics evaluation by means of pulsed ultrasonic Doppler velocimetry
technique through Polish pneumatically driven extracorporal ventricular assist
device (VAD).
Methods: The numerical model based on advanced computer modeling
techniques supported by computer fluid dynamics analyses has been performed.
The physical model has been produced and finally the hydrodynamic evaluation
concerning flow velocity distribution, shear and Reynolds stress with usage of
ultrasonic Doppler velocimetry has been investigated. Numerical calculations
have been performed for diastolic diaphragm position, steady state condition
and maximum disc opening angles. Model based on high quality numerical mesh
with the inflation layers. The CFD results have been related to the experimental
ones, the results analysis has been done and the numerical model adaptation
has been performed in the following step. Finally the verified CFD model has
been achieved.
Results: Fluid velocity profiles with stagnation regions taken under
consideration, shear stress and pressure distribution regions have been
analyzed. The evaluation has been done in locally chosen critical pump areas
and globally through the pump volume.
Conclusions: Performed flow analyses allowed to answer asked questions
concerning flow condition according to the pump blood contacting surface
architecture. The future work concerning optimizing the pump inlet assembly
supported with numerical and hydrodynamic evaluation will improve flow
condition inside the pump.
Acknowledgements: The work has been performed within the settings of the
Polish government program “Polish Artificial Heart” which incorporates five
different heart support prostheses, where finally the evaluated VAD is going to
be one of them.
P110 (165)
INFLUENCE OF THE TYPE OF ARTIFICIAL VALVE ONTO THE FLOW INSIDE
OF PEDIATRIC ARTIFICIAL HEART
W. Bujok1, D. Obidowski2, A. Kapis1, R. Kustosz1, K. Jozwik2, P. Reorowicz2,
P. Klosinski2
1
Artificial Heart Laboratory/Foundation for Cardiac Surgery Development,
Zabrze, Poland; 2Institute of Turbomachinery, Technical University of Lodz,
Lodz, Poland
Objectives: Numerical flow analysis through mechanical three-leaflet valve
which is being designed for application in Polish pediatric ventricular assist
device (POLVAD-PED), with reference to single heart valves (Medtronic Hall™)
and J.J. Moll was the aim of this work.
Materials and Methods: Three different types of artificial heart valves were
tested with CFD methods. Commercial single disc (Medtronic Hall™), designed
in the Institute of Turbomachinery valve based on the J.J. Moll concept and one
three-leaflet polyurethane valve designed in the Foundation for Cardiac Surgery
Development were analyzed. Non-Newtonian blood model based on the Power
Law model was implemented. Tests were conducted in steady state mode for
characteristic time points of the cardiac cycle. Flow patterns were analyzed
and compared. The main comparison criteria used in the presented study were
homogeneity of the flow and stagnation regions.
Results: Numerical experiment conducted showed that single disc valves gives
better flow inside of the artificial heart chamber, especially when stagnation is
concerned, when compared with polyurethane valve. The same was observed
© 2010 Wichtig Editore - ISSN 0391-3988
for homogeneity criteria. Observed swirls inside of the blood chamber are nearly
axisymmetric with respect to the axis of the chamber. This helps to swill out
blood surfaces of the blood chamber. In the case of polyurethane valve flow
described with the chosen parameters was much worst.
Conclusions: Comparison of the three valves showed clear superiority of the
single disc valves, especially for the J.J. Moll, with respect to the polyurethane
one. It has to be emphasised that one of the crucial parameter that influences
the flow inside the artificial heart chamber is the angular position of the single
disc valve. In case of polyurethane valve the angular position changes, due to
its characteristic design, although it was not taken into consideration in the
present experiment.
P111 (106)
The effect of pump obstructions in a continuous flow left
ventricular assist device
J.R. Martina1,2, B.F.M. Rodermans1, E. Sukkel1, K.A.M.A. Pennings2 M. Rutten2,
J.R. Lahpor1
1
University Medical Center, Utrecht; 2Eindhoven University of Technology,
Eindhoven, The Netherlands
Objectives: Ventricular support by continuous flow left ventricular assist
devices (cf-LVADs) may become limited due to an obstruction within the conduit
of the pump. However, these obstructions may remain undetected and progress
further causing larger complications. We investigated the hemodynamic effects
of pump obstructions in a continuous flow LVAD using a static mock loop.
Methods & Results: We simulated obstructions of 0%, 50%, 75% and 90% of
the area of the inflow cannula of the cf-LVAD. Hemodynamic parameters (flow
and pressure) were measured at pump speed settings between 6000 and 12000
rpm. HQ-curves of the pump characteristics were made and alternative HQ-
curves were measured including the pump obstructions.
A significant difference of 1.6 liter/minute was observed between measured
flow and estimated flow provided by the LVAD (P less than 0.05). A significant
decrease of the pressure difference over the device (delta P) was observed for
obstructions of 75% and higher due to the pressure changes caused by the
obstructions. The HQ-curves were different from the alternative HQ-curves with
the obstructions. However, power and estimated flow characteristics of the
LVAD did not change for all obstructions.
Conclusions: As pump characteristics remained unchanged during an inflow
obstruction, pump-derived hemodynamic parameters may not agree with the
actual hemodynamic parameters during support in the presence of pump
obstruction.
P112 (187)
AORTIC WASHOUT AND SHEAR CAUSED BY RIGHT AXILLARY
CANNULATION
S. Vandenberghe1, H. Tevaearai2, T. Carrel2, S. Demertzis2
1
ARTORG, Bern, Switzerland; 2Inselspital, Bern, Switzerland
Right axillary artery cannulation (RAAC) is accepted as an alternative for aortic
cannulation with cardiopulmonary bypass. It is also an option for the outflow of
miniature ventricular assist devices (VADs). We aimed to quantify and visualize
washout and stagnation in the ascending aorta for several assist and flow level
scenarios with RAAC.
A transparent silicone model of a human aorta with all major branches from
the aortic valve (polyurethane trileaflet) to the diaphragm was mounted in a
flow circuit. A Thoratec VAD simulated left ventricular function and a centrifugal
pump (CP) with RAAC was used for extracorporeal support. Flow distribution
was controlled with Hofmann clamps on each branch and physiological flow
and pressure waveforms were achieved. Five different flow distributions were
tested: VAD/CP (l/min): 5/0, 4/1, 2.5/2.5, 1/4, 0/5. For washout assessment,
colorants were injected in an automated fashion in the brachiocephalic trunk.
For direct visualization of shear, a crystalloid suspension was illuminated with
polarized light. Flow patterns were captured on video and analyzed using
quantitative 2D image processing.
With increasing assist level, pulsatility decreased: pulse pressure dropped
from 80 to 2 mmHg and Surplus Hemodynamic Energy from 28500 to 86 ergs/
cm. This resulted in distinct flow patterns in the carotid arteries. Systolic flow
pulses of the 5/0 case yielded the highest shear levels in the ascending aorta.
Retrograde flow (brachiocephalic trunk to aortic valve) was more prominent with
higher assist levels: the ratio of peak retrograde to peak antegrade flow went
as high as 59%. Consequently, longer washout times were found (0.8s for 5/0
vs. +6.0s for 0/5), and stagnation in the ascending aorta was observed at full
support.
Continuous flow entering the aorta from the brachiocephalic trunk is divided
471
Int J Artif Organs 2010 ; 33 ( 7): 472
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
in retro- and antegrade flow. Increasing contribution of RAA-flow increases
retrograde flow and reduces washout of the ascending aorta, while averaging
out shear rates. The physiological impact of these findings needs to be assessed
in additional studies.
Cardiac clinical
P113 (183)
THE IMPORTANCE OF AN INTERNATIONAL HYPOTHERMIA REGISTRY
FOR IMPROVING THE OUTCOME OF ACCIDENTAL HYPOTHERMIA
VICTIMS
M. Meyer1, E. Khabiri1, M. Licker2, Y. Gasche2, P. Baumann3, A. Kalangos1,
B.H. Walpoth1
1
Cardiovascular Surgery; 2Anesthesiology, Intensive Care; 3Medical IT, Geneva
University Hospital, Switzerland
Objectives: Transient mild hypothermia is common and usually without
consequences for the brain or other organs. However, prolonged deep
hypothermia (body temperature <28°C) due to accidents is relatively rare and
usually associated with premature death due to cardiopulmonary arrest and can
be successfully resuscitated by Cardio Pulmonary Bypass (CPB) rewarming.
Our aim was to create an International Hypothermia Registry (IHR) to improve
outcome of deep accidental hypothermia victims.
Methods: We therefore created an internet-based IHR to collect and analyze
relevant information about accidental hypothermia in the hope of establishing
guidelines for prevention, treatment and outcome of such victims. In a pilot
phase, we analyzed 6 cases treated in our centre in 2008. The predominant
cause was suicide attempts followed by cold exposure.
Results: Three victims survived with minor damage, 3 died shortly after
rewarming. The 3 surviving victims had experienced cardiorespiratory arrest and
core temperatures below 26°C. All victims arrived with CPR, were rewarmed with
CPB and could be discharged without sequelae. The 3 non-surviving victims
were young, without vital signs at rescue with core temperatures between 28-
29°C and normal potassium levels. However, all died after successful rewarming
and weaning from CPB due to fulminant haemorrhagic pulmonary oedema.
Conclusions: Our limited experience from 2008 shows once again the
importance of witnessed cardiac arrest combined with deep hypothermia for
a positive outcome. The 3 fatal cases were in cardiac arrest of unknown time
and most likely not attributable to hypothermia. The entry of these pilot cases in
our internet-based IHR was helpful to standardize the data in order to elaborate
better outcome predictors. Data of the IHR will be collected worldwide and a
peer-reviewed analysis by an International Working Group should establish new
consensus guidelines for the treatment of accidental hypothermia victims.
P114 (301)
LEFT VENTRICULAR RECONSTRUCTION AND BYPASS GRAFTING ON
BEATING-HEART SETTINGS
Z. Mitrev, T. Anguseva
Special Hospital for Cardiosurgery “Fillip II”, Skopje, R. Macedonia
Objectives: The aim of study was to evaluate clinical results of CABG and left
ventricle (LV) surgical remodelling in off-pump settings.
Methods: On 33 selective patients after bypass grafting we have done LV
surgical reconstruction of dyskinetic area, with ventriculoplasty of LV wall on
beating-heart. Including criteria were: severe coronary disease, enlargement of
LV, presence of LV dyskinetic area. Excluding criteria were: presence of mitral
regurgitation >+2. After medial sternotomy and standard grafting, on border
line with normal myocardium we placed circularly suture. We pulled suture,
excluding aneurysmatically changed myocardium. With over and over suture
we made additionally fixation keeping normal geometrical LVform.
Results: All patients get total arterial revascularization with LITA on LAD (33 pts),
RA as “T graft” on rpld (15 pts), as “jump” on rms in 72 pts. EDV/ESV was
decreased from 228/161 on 172/102 with increasing of EF from 20% on 32%
postopeartively. CO/CI pre-operatively were 2.9/1.8 with increasing on 4.6/2.9
postoperatively. IABP was applied on 2 pts pre-operatively. ICU data showed
shorter intubating time (6.5h), no liver or kidney complications, less drainage
and need for transfusion. In-hospital stay was 6 days, NYHA class from IV on II
group. Follow-up period is 10 days-12 months.
Conclusions: This combined surgery in off-pump settings allows safe restoration
of ventricular geometry, better clinical outcome and rare postoperatively
complications.
472 © 2010 Wichtig Editore - ISSN 0391-3988
P115 (298)
Is there a less invasive thoracoabdominal aortic aneurysm
repair?
Z. Mitrev, T. Angjusheva, N. Hristov
Special Hospital for Surgery “Filip Vtori”, Skopje, R. Macedonia
Objectives: This paper will present our experience with the use of DeBakey
type repair for thoracoabdominal aortic aneurysm (TAAA).
Methods: 4 male patients (55±7 years) were treated in our center for TAAA.
They were symptomatic; aneurysm dimension of 10±2 cm. One patient
had ongoing rupture for Crawford type I TAAA -aneurysm of aortic arch,
developed after ascending aorta and hemiarch graft replacement previous
aortic dissection. The other were Crawford III. Surgery was performed through
thoracophrenolaparotomy, employing DeBakey type repair with construction
of composite end-to-end prosthesis between tubular and bifurcated graft and
proximal end-to-side prosthesis implantation on thoracic aorta. In 1 patient we
performed proximal end-to-side prosthesis implantation on previous ascending
aortic prosthesis with reimplantation of cranial vessels and end-to-end
anastomosis with both iliac arteries, followed by implantation of celiac trunk,
superior mesenteric and renal artery over 10 mm vascular graft.
Results: Patients remained hemodinamically stable. 2 patients had minimal
blood loss and were discharged on 8-10-th postoperative day. 2 patients
required prolonged ventilation and postoperative use of cell-saver. 1 patient,
who had previous laparotomy, developed infection. The other had prolonged
ventilation, tracheostomy, intestinal bleeding, sepsis and paraplegia. He is still
on intensive recovery.
Conclusions: DeBakey type repair is a less invasive approach. Without the use
of extracorporal circulation and reduced ischemic time, this technique avoids
inevitable operative complications encountered with hypothermic circulatory
arrest, partial cardiopulmonary bypass, partial left heart bypass, or clamp-and-
sew strategy.
P116 (299)
Surgical treatment of aortic aneurysms in a patient with
Ehlers-Danlos syndrome
Z. Mitrev, T. Anguseva, V. Belostotckij, V. Petrovski, N. Hristov, E. Idoski
Special Hospital for Surgery “Fillip II”, Skopje, R. Macedonia
Ehlers-Danlos syndrome is a rare inherited disorder of the connective tissue that
has been divided into 10 types according to the clinical course and inheritance.
In type IV Ehlers-Danlos syndrome extreme fragility of the arteries is associated
with multiple aneurysm formation, spontaneous rupture, and dissection.
We report on a patient with Ehlers-Danlos syndrome who had enlargement
of the sinus of Valsalva, severe aortic and mitral valve regurgitation. Surgery
for aneurysm of the aortic root, and mitral valve reconstruction had been
performed.
Clinical summary: A 36-year-old man was admitted to our department for the
treatment of enlargement of the sinus of Valsalva. His height was 180 cm and
weight was 60kg. There were characteristic findings in the skin and joints, with
prognatia and gothic mouth. He had received graft replacement for an ascending
aorta with reconstruction of the aortic rooth combined with mitral valve
reconstruction. Ehlers-Danlos syndrome was diagnosed histopathologically by
staining of the resected aortic wall, which showed deficiency of type III collagen.
Early postoperatively the patient had severe bleeding due to coagulation
disorders. Later postoperative period was uneventful, except an enormous
thoracic bulla of the right lung, which was treated conservatively with a thoracic
drainage. After 20 days the patient was discharged home.
P117 (302)
Carotidal by-pass surgery for chronic total occlusion of
the internal carotidal artery
Z. Mitrev, T. Anguseva, N. Hristov, V. Petrovski, A. Jankulovski
Special Hospital for Surgery “Fillip II”, Skopje, R. Macedonia
Objectives: Treatment of symptomatic chronic totally occluded carotid artery has
been limited to medical management. An ongoing clinical trial is examining the role
of extracranial to intracranial bypass surgery in selected patients with impaired
cerebrovascular reserve based on PET imaging parameters. We describe our
experience utilizing bypass surgery to treat a chronic total carotid occlusion.
Materials and Methods: Four patients presented with a hemispheric ischemic
stroke in the setting due to a total occlusion of one of the internal carotid artery.
64MSCT scan showed cerebral circulation after total carotidal occlusion. All patients
were on antiplatelet therapy and oral vasopressor agents. Thromboendarterectomy
followed by bypass surgery was performed in all four patients.
Int J Artif Organs 2010 ; 33 ( 7): 473
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
Results: Two patients got thromboendarterectomy followed by direct carotidal
artery closure, one who had severe stenosis of the right corotidal artery and
occlusion of the left internal one, got thromboendarterectomy of the right internal
carotid and albograft PTFE 6mm revascularization from the right one to the left
one. And the last patient was with thromboendarterectomy and patch plasty of
the left internal carotidal artery. Control 64MSCT scan showed normal carotidal
and intracranial circulation. There was no neurological symptomatology in all
four patients. Follow-up period was 1 to 12 months.
Conclusions: Carotidal by-pass surgery can be a therapeutic option in selected
patients with chronic total carotid occlusion. Further study is required to
determine the safety profile of this treatment modality.
P118 (65)
CIMS BALLOON PUMP
A.Z.M. Khudzari1, D. Richens2, G.D. Tansley3
1
University Teknologi Malaysia, College of Science and Technology, Kuala
Lumpur, Malaysia; 2Department of Cardiothoracic Surgery, University Hospitals
Nottingham, UK; 3Aston University, School of Engineering and Applied Science,
Birmingham, UK
Heart failure (HF) continues to be one of the leading causes of mortality across
the world. Several treatment modes are available for HF from medical therapies to
heart transplantation. We describe here a novel treatment mode named Chronic
Intermittent Mechanical Support (CIMS) aimed at patients who are refractory
to medical therapies and who are ineligible for heart transplantation. CIMS
comprises a displacement-type balloon pump implanted in ascending aorta, a
percutaneous driveline, and an external ambulatory driver console. The CIMS
blood pump uses counterpulsation to augment blood flow through reduction
in left ventricular (LV) afterload and improvement in coronary artery flow. With
reduction in LV afterload we expect reduced left ventricle workload and it is
believed that this may initiate some level of myocardial reverse remodelling.
The objective of this study was to determine the effectiveness of CIMS balloon
pump concept: a prototype CIMS balloon pump was developed and used in vitro
in a LV human mock circulatory loop (MCL) which incorporated a physiological
shape silicone aorta to better simulate LV physiological circulation. The MCL
was programmable to simulate various heart conditions and several balloon
pump prototypes were tested – all powered by an Intra Aortic Balloon Pump
driver. Data measured were LV and aortic pressure waveform, aortic flowrate,
and systolic LV volume changes. From those data, cardiac output, afterload
changes and LV systolic work were computed.
In early prototypes, mean cardiac output increased on average by 6% while afterload
decreased by 13%. LV systolic work difference due to counterpulsation confirms
that the CIMS balloon pump delivered satisfactory LV workload reduction.
P119 (304)
TRANSCATHETHER VSD CLOSURE AFTER CARDIAC SURGERY IN
PATIENT WITH Sy EISENMANAGER - case report
Z. K. Mitrev1, T. N. Anguseva1, I. Milev1, D. Schranz2
1
Special Hospital of Cardiosurgery, Skopje, R. Macedonia; 2Cardiosurgery
Centre Justus Liebig, Gissen, Germany
Background: 41-year-old male with end-stage heart failure; congenital
malformation of mitral and tricuspid valve, ventricular septum defect (VSD);
severe pulmonary hypertension. He was cyanotic (O2Sat.56, Hb-16, Htc-45).
Using transoesophageal echocardiography VSD, pulmonary artery (38mm),
severe mitral and tricuspid regurgitation have been visualized (EF=15%,
EDV=265mL, ESV=202mL).
Methods: After mild cardioplegia, mitral and tricuspid annuli reconstruction,
pulmonary artery (PA) was banded on 24mm to increase right-to-left shunt and
decrease aortic saturation, with consequent decrease in PA saturation. Lowered
PA saturation results in decreasing of pulmonary resistance, opening closed
capillary pulmonary net improving O2 diffusion in pulmonary vein O2 Sat. in
patient was increased on 82 from 56 (without O2), and Hb was kept on 14
with Htc on 45-50, postoperatively. Hemodynamic measurements during the
first 5 days showed that PA pressure was 50% of systemic pressure. After 2
years, due to relapse of mitral insufficiency, patient got mechanical mitral
valve with closure of membranous VSD with pericardial patch. Implantation of
permanent pace maker was performed due registrated AV block IIIrd degree.
After 6 months control ultrasound examination showed big VSD muscular part
of septum. The patient was prepared for VSD device closure, which was a last
separate intervention.
Conclusions: Hybrid technique of VSD transcathether closure in patients after
previous cardiac surgery intervention can be a preferred approach, less invasive
for the patient with good clinical outcome.
© 2010 Wichtig Editore - ISSN 0391-3988
P120 (158)
Profiling for Partial circulatory support
S. Jacobs, J. Geens, F. Rega, W. Droogne, H. Bollen, B. Meyns
KU, Leuven, Belgium
Objectives: Recently a rotational micro-pump (SynergyTM micro pump,
CircuLite® Inc.) has been developed, which delivers partial circulatory support.
In our institution we have implanted 14 Synergy micro-pumps. In the same
period we implanted 29 HeartMate IITM devices. Patient files were reviewed to
profile the characteristics of patients suitable for partial support versus patients
requiring full support.
Methods: We reviewed preoperative biochemical, hemodynamic and clinical
data. We compared these preoperative data between patients on partial support
(Group CL, SynergyTM micro-pump) and patients on full support (Group HM,
HeartMate IITM). Additionally we differentiated good and bad responders in
patients with partial support.
Results: Age, gender and BSA were comparable between both groups. There
were significantly more patients with dilated cardiomyopathy in Group HM
(Group CL: 2/14 versus Group HM: 15/29; p<0.01). The average INTERMACS
score was higher in Group CL (Group CL: 4.1 versus Group HM: 2.6; p<0.0001).
No difference in preoperative biochemical values could be retained, except higher
CRP levels in Group HM (Group CL: 11.7mg/L versus Group HM: 77.1mg/L;
p<0.05). Preoperative hemodynamic measurements showed a higher systolic and
mean pulmonary artery pressures in Group CL (59.4mmHg versus 47.6mmHg;
p<0.01) and 40.9mmHg versus 34.6mmHg (p<0.05) respectively). No differences
in systemic perfusion pressure, cardiac output or cardiac power were observed.
Twenty-two patients in Group HM were on inotropic support compared to 2 in
Group CL (p<0.0001). Three patients on partial support were defined as bad
responders. Two of these patients had dilated cardiomyopathy (p<0.001). There
was a trend towards lower systolic and mean pulmonary artery pressures.
Conclusions: We tried to determine a patient-profile of patients eligible for
partial support. The ideal candidate for partial support is middle-aged, has an
ischemic cardiomyopathy with good right ventricular function and INTERMACS
score 4 or higher.
P121 (194)
THE EXPLANTED PROSTHESES STUDY - OBLIGATION OR LUXURY?
Z. Nawrat, Z. Małota, J. Sliwka, P. Kostka, J. Nozynski, L. Łachecka, R. Wojnicz,
J. Lelatko, A. Dworak. M. Jakubowski
Foundation for Cardiac Surgery Development, Medical University of Silesia,
Silesian University, CMPiW PAN, Katowice, Poland
Background: The Core Laboratories for investigation of failed cardiovascular
implant materials, initiated by the UE grant COST Action 537, thanks to Polish
grant, have been organized in Poland.
Objectives: For FCSD, research centre working on heart prostheses, biomaterials
and new surgery tools the goal is the improvement of medical devices in clinical
practice from the analysis of implanted prostheses. Supported by a scientific
multidisciplinary team, physicians can recognize the reason of the surgical
intervention and exchange the prostheses.
Materials and Methods: The protocol for the recovery and evaluation of the
implants and surrounding tissues consists of significant information about
the patient and the explanted device/biological materials. The study includes
histopathology, chemical analysis, surface studies. The complex analysis of
valve damage reasons & their consequences have been studied using different
modeling method: physical and computer simulation.
Results: Several critical outcomes were elicited by experimental analyses, such
as evidences of materials preservation/degradation, surface interactions with
plasma proteins, materials colonization by fibroblasts or inflammatory cells, etc.
About 200 samples: heart valves and vessel prostheses and vascular stents are
under investigation.
Conclusions: The test of chosen samples gave interesting answers to both
physicians and engineers questions. Different mechanisms were shown to occur,
causing the need for devices explantation, including calcification phenomena,
thrombosis and infective processes. In conclusion, the results obtained in the
course of the study enhanced some of the problems concurring to the behavior
of blood-contacting biomaterials and contribute to describe the complexity and
variety of the phenomena occurring in vivo. Described results can be used in
the diagnosing patients data analysis in case, when the reason of progressive
pathology changes is well known.
473
Int J Artif Organs 2010 ; 33 ( 7): 474
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
Transplantation
P122 (288)
Correlation Between the Severity of Liver Disease and image
analysis of histological findings. Preliminary studies
F. Marinozzi, S. Novelli, V. Morabito, G. Novelli
Sapienza University, Rome, Italy
Objectives: Cirrhosis is the end result of chronic liver disease and complications
of cirrhosis, including esophageal varices and ascites, develop once portal
pressure reaches a threshold level of 10–12 mmHg, as assessed by the hepatic
venous pressure gradient (HVPG). Liver biopsy remains the gold standard for
staging diffuse liver disease. But in liver disease the histologic examination can
not determine or predict the onset of disease complications and mortality of
patients. Recent studies have shown a modest correlation between HVPG and
histologic findings and in particular the septal thickness and nodule size. The
aim of the study is to assess whether there is a correlation between the HVPG
value and the modifications of morphology of sinusoids.
Materials and Methods: Four patients with biopsy-proven cirrhosis and HVPG
measurements within 1 month of the biopsy were included in the study. Two
patients were affected by C virus related cirrhosis and two by alcohol related
cirrhosis. Patient [1] and [4] showed an HVPG = 11 mmHg, patient [2] an HVPG=
12 mmHg and patient [3] an HVPG = 14 mmHg. Patient [5] was considered
as “control patient” with a normal HVPG and histologic finding negative for
cirrhosis.
Results: In the patients, we conducted an analysis of the geometrical images
of individual histological changes of sinusoids. Summarizes the results for each
class of samples, both in frequency domain by calculating the spatial Fourier
Transform (FT), which by the morphological parameters such areas and spatial
distributions of sinusoids. The aforementioned parameters are then compared
with histology of “control patient”. This method has shown a change in the
morphology of sinusoids in relation to the value of HVPG in the 4 patients
with the evaluated cirrhosis. As expected, in the control patient any kind of
morphological abnormality was seen.
Conclusions: Establishing the concept of ‘severity of cirrhosis’ has significant
clinical implications. Upon diagnosis of cirrhosis, specific histological findings
on biopsy could predict the likelihood of complications or death of patient.
This correlation between geometric analysis of images of individual histological
changes of sinusoids and HVPG could be predictive of the clinical evolution of
cirrhosis. These results are not statistically significant, but suggestive to apply
this methodology in a larger number of patients.
P123 (149)
NGAL AS A MARKER OF GRAFT FUNCTION IN THE EARLY POST-RENAL
TRANSPLANT PERIOD
K. Nisi, G. La Manna, I. Capelli, N. Lanci, G. Ubaldi, G. Comai, M.L. Cappuccilli,
M.P. Scolari, S. Stefoni
Nephrology, Dialysis and Renal Transplant Unit, S. Orsola University Hospital,
Bologna, Italy
Objectives: Neutrophil Gelatinase-Associated Lipocalin (NGAL) has been
recently proposed as a novel early marker for detection of acute changes in
kidney function. The increase in NGAL production and release from tubular cells
during acute damage leads to a subsequent elevation in its serum and urine
levels. In renal transplantation, a correlation of NGAL either with acute rejection
or with Cyclosporin A (CsA) nephrotoxicity has been proven. The purpose of the
current prospective study was to assess whether serum and urine NGAL can be
used as reliable markers in a 3-month follow-up period after transplant.
Methods: Blood and urine samples from 33 kidney patients who received kidney
transplant at out centre between January and November 2009 were collected
before transplant and after 1, 7, 14 days, 1 and 3 months. The urine and serum
NGAL were assayed using a commercially available ELISA.
Results: A significant and gradual decrease in serum NGAL levels was found
within 3 months following kidney transplantation (p=0.0001). The data collected
revealed a positive correlation between the trends of serum NGAL and creatinine.
Serum NGAL showed significant differences at 1, 3, 7, 14 days after transplant
(p=0.013; p=0.002; p=0.001; p=0.003, respectively). We observed that those
patients whose NGAL serum levels exceeded 200 ng/mL at 7 days, had higher
creatinine levels at all the experimental times compared to the patients with NGAL
serum levels within 200 ng/mL at 7 days (p=0.001). Our results also highlighted
a significant rise of NGAL urine and serum levels in patients with delayed graft
function (DGF), compared to those with immediate graft function recovery. Urine
NGAL was increased in DGF patients at 3 and 7 days (p=0.002; p=0.006).
474 © 2010 Wichtig Editore - ISSN 0391-3988
Conclusions: Our results suggest a positive correlation between serum NGAL
and creatinine levels in the early post-transplant period. Moreover this study
indicates NGAL urine and serum levels as predictive biomarkers for DGF in
kidney transplant.
P124 (111)
WEIGHT GAIN AND LIPID ABNORMALITIES AFTER RENAL
TRANSPLANTATION
A. Strakosha, N. Pasko, A. Idrizi, V. Cadri, S. Kodra, N. Thereska
Nephrology UHC “Mother Tereza” Tirana, Albania
Objectives: A tendency to weight gain is common after renal transplantation
and is of concern because of the associated risk with post-transplant
cardiovascular morbidity and diabetes mellitus. The aim of this study was to
define the occurrence and magnitude of the weight gain and its relationship to
gender, hypertension and lipid abnormalities after renal transplantation.
Methods: We conducted a retrospective study. The cohort included 57 patients
(15 females, 42 males, mean age: 33.78±9.78 years) who were recipients
of kidneys from living-related donors. Patient data on weight, cholesterol,
tryglicerides, and arterial pressure were collected from medical records at 3,
6, 9 and 12 months after renal transplantation. All patients were on the same
immunossupressive therapy with cyclosporine, mycophenolate mophetil and
corticosteroids.
Results: Although at baseline none of the patients was overweight, at one year
after transplantation 21 patients (36%) showed a significant increase in mean
weight (5.9±9.2 kg, p < 0.001). Additionally, a lesser post-transplant weight
increase was noted in females compared with males, but the difference was
not significantly different between sex. In patients who showed increased
weight, a progressive increase in total cholesterol and triglycerides levels
was also observed. Mean serum cholesterol levels before and one year after
renal transplantation were 145.15±12.6 and 212.82±4.58 mg/dL (p < 0.001)
respectively. Triglycerides levels were 137.11±08 and 186.15±12.5 (p < 0.001)
respectively. We found a statistically significant increase in the incidence of
post-transplant hypertension at one year follow-up.
Conclusions: According to the results of our study the weight gain one year
after renal transplantation was significantly associated with increasing of
cholesterol and triglyceride levels and remains an additional risk factor for
hypertension. Optimal control of weight after renal transplantation including diet
with an adequate carbohydrate and lipid content is indeed necessary in order to
prevent weight gain, hypertension and lipid abnormalities.
P125 (338)
CREATININe REDUCTION RATIO ON DAY 2 : USEFUL MARKER FOR LONG-
TERM TRANSPLANT OUTCOME IN RENAL ALLOGRAFT PATIENTS
I. Rambabova-Busljetic, J. Masin, G. Selim, P. Kolevski, Z. Popov, N. Ivanovski
University Clinics of Nephrology, Urology and Transfusiology, Medical Faculty
Skopje, R. Macedonia
Objectives: Early graft recovery is a confirmed beneficial factor for long-
term graft survival. On the other hand, delayed graft function is a common
complication after renal transplantation especially when expanded criteria renal
donors are used. Due to the underdeveloped cadaveric renal transplantation,
our centre performs predominantly living donor transplants. Although the DGF
is defined as a need of dialysis after renal transplantation, we introduced a
criterion of creatinine reduction ratio between day 1 and 2 (CRR2) as a better
marker for long-term graft survival. Here we present our first experiences.
Methods: A retrospective study was performed in 113 living renal transplant
recipients transplanted in the last 5 years. As living donors the following were
accepted: 85 haploidenthical parents, 5 sisters, 2 grandmothers, 3 aunts and 18
unrelated donors (predominantly spousal). The sequential quadruple protocol
with IL-2R antagonist and triple drug (MMF, CyA and steroids) maintenance
immunosuppression was used in all patients. The donors’ mean age was 61
years (range 28-84), while the recipients’ 39 years (range 18–66 years). The
mean warm and cold ischemia times were 3.7’ and 3.8 h, respectively. According
to RR2, the whole group of patients was divided into first one (group I, n=45)
with RR2>30% and second one (group II, n=68) with RR2<30%. There were no
significant differences between the groups in the donor’s age (61±6 vs. 63±4),
pretransplant GFR (80 vs. 75 ml/min), recipient’s age (40+9 vs. 40±12), warm
ischemia time (4±1.4 vs. 3.5±1.4 min), cold ischemia time (225±106 vs. 210±42
h) and HLA mismatch (2.4 vs. 2.6). The serum creatinine and GFR were evaluated
during the first week, on 30th postoperative day and 24 months later.
Results: There was a significant difference in the first postoperative week in
serum creatinine between group I and II (82.8±42 vs. 260±46), on day 30th
(97.6±20.4 vs. 140±5) as well as 24 months later (121±8 vs. 151.8 μmol/L).
Int J Artif Organs 2010 ; 33 ( 7): 475
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
The GFR was also superior on day 7 (76.9±13 vs. 41.3±2) on day 30 (77.8±2.
vs. 56.8±2) as well as 24 months later (70.3 vs. 51.3 ml/min). There was no
difference between rejection episodes (12% vs. 14%), graft lost (5 vs. 6) as well
as surgical and medical complications, respectively.
Conclusions: Our results confirmed that CRR2 correlates with renal function
throughout the first two years after transplantation. CCR2 is a useful easily applied
marker of DGF. Defining DGF by CRR2 allows an objective and quantitative
diagnosis after transplantation and can help to modify the immunosuppressive
protocols in the early period after surgery.
P126 (320)
USE OF ELDERLY LIVING KIDNEY DONORS – 20 YEARS EXPERIENCE iN
THE BALKANS
N. Ivanovski, J. Masin, P. Kolevski, K. Cakalaroski, Z. Popov
University Clinics of Nephrology and Urology, Institute of transfusiology, Medical
Faculty, Skopje, R. Macedonia
Objectives: In the last 20 years the Balkan region has dramatically changed.
Despite the efforts for transplants, dialysis remains the usual way of treatment
of ESRD. The living renal transplantation (LRT) is still predominant but there
is an enormous gap between the demand and supply of kidneys. Trying to
solve the problem, we started with our policy to accept the so-called expanded
criteria living kidney donors including elderly (ED), marginal, unrelated and
ABO incompatible donors. In this study we presented our 20 years’ experience
with living renal transplantation using elderly kidney donors, some of them in
advanced age.
Methods: Two hundred and forty-five LRT have been performed in our
Renal Transplant Unit in the last 20 years. In 95 of them the predominantly
haploidenthical living donors were older than 65 years, but 33 older than 70 (ED).
The donors’ mean age was 69±3 (range 65-86). The recipient group consisted
predominantly of haploidentical children, with mean age of 45 ± 6 years (range
35-58). The quadruple sequential immunosuppressive protocol was used in
all cases including induction with ATG or Il-2R antagonists and Cyclosporine
A, MMF/AZA and Steroids as a maintenance therapy. The Kaplan-Meier one,
three and five year’s graft and patient survival rate, rejection episodes, delayed
graft function (DGF) and actual renal function were analyzed. The results were
compared with the group of 110 LRT with younger donors (mean age 51±5,
range 38-62 years) and their haploidenthical recipients (mean age 35±4, range
16-42 years) performed in the same time (YD).
Results: One, three and five years Kaplan-Meier graft survival rate for the ED was
94%, 82% and 65%, respectively, compared with 95%, 88% and 77% of YD
group (p<0.04) while patient’s survival rate was 94%, 90% and 85 compared with
98%, 89% and 86%, respectively (p>0.6). The percentage of DGF was 15% in
ED group compared with 8% in YGD. Both differences are statistically significant.
The rejection episodes rate in ED and YD was 16% and 19%, respectively and the
actual serum creatinine in ED was 178, compared with 159 μmol in the YD. The
last two differences are not statistically significant. There were no serious medical
and surgical complications among the elderly and younger kidney donors.
Conclusions: Despite the statistical (acceptable) difference in graft survival
after 5 and more years between the ED and YD, the results in our study fully
justify the use of ED especially in the regions where the LRT is predominantly
a transplant activity. ED are available and their use is much easier and cheaper
compared with the very good organized cadaveric transplantation with the
comparable graft survival. As elsewhere, it may ameliorate the actual organ
shortage in the Balkans.
P127 (45)
Less frequent clinical manifestations of CMV-disease in
renal transplant recipients
N. Bašić-Jukić, L. Bubić-Filipi, I. Ratković-Gusić, P. Kes
Department of Dialysis, University Hospital Centre Zagreb, Zagreb, Croatia
Objectives: Diagnosis of cytomegalovirus (CMV) disease requires detection
of CMV (serological, RT-PCR) accompanied with clinical signs and symptoms.
The most common clinical findings of CMV disease include fever, followed by
leukopenia, thrombocytopaenia, deterioration of graft function and hepatitis. We
investigated involvement of other organs by the CMV.
Materials and Methods: Retrospective evaluation, and from the year 2003
prospective follow-up of renal transplant recipients to determine frequency,
severity and consequences of rare clinical manifestations of CMV disease.
Serology was used until 2005, and since that time we use PCR for quantitative
determination of CMV infection. We use prophylactic strategy which involves
administration of antiviral agents (ganciclovir, and more recently valganciclovir)
to patients at increased risk for infection.
© 2010 Wichtig Editore - ISSN 0391-3988
Results: From January 1973 to October 2009, 1054 patients received kidney
allograft at our institution. During that time, CMV infection defined as positive
CMV by either serology or PCR, was demonstrated in 134 patients (51 treated
with Azathioprine, and 83 treated with mycophenolate mofetil). CMV colitis
was diagnosed in a female patient after bowel rupture 2 months following renal
transplantation. Despite the treatment with ganciclovir and CMV hyperimmune
globuline, she developed CMV encephalitis and died from disseminated CMV
disease. Severe gastritis occurred 45 days after renal transplantation in a female
patient. Esophagogastroduodenoscopy revealed patchy distribution of mucosal
lesion. PCR and mucosal biopsy proved CMV disease. Spleen damage indicated
by occurrence of Howell-Jolly bodies in the peripheral blood was demonstrated
in one patient. After observation of blood irregularity, testing demonstrated CMV
infection which was successfully treated with ganciclovir. Heavy pancytopaenia
with presence of blast cells and changed morphology of megakariocytes
with consequent heavy thrombocytopaenia was consequence of resistant
CMV disease in a male patient. Eight patients had CMV pneumonitis. Other
patients had usual CMV organ involvement with febrility, nephritis, hepatitis and
myelotoxicity.
Conclusions: Timely recognition of CMV disease may be life-saving in
immunocompromised patients. It seems that CMV may attack any organ in the
body. Further studies are needed to determine the optimal treatment strategy to
avoid development of CMV disease.
P128 (319)
ABO-INCOMPATIBLE LIVING DONOR TRANSPLANTATION - THE FIRST
CLINICAL EXPERIENCE IN SKOPJE
G. Severova Andreevska, J. Masin, S. Pavleska, P. Kolevski, I. Rambabova–
Busljetic, Z. Popov, N. Ivanovski
University Clinics of Nephrology, Urology and Institut of Transfusiology, Medical
Faculty, Skopje, R. Macedonia
Objectives: Due to the severe organ shortage and underdeveloped cadaveric
renal transplantation in the Balkans we started accepting expanded criteria
living donors including elderly, marginal and unrelated donors. In the last years
ABO-incompatible renal transplantation has started, too. The first four cases
are presented here.
Methods: A 40-yr mother (blood group A1B), 57-yr husband (B), 46-yr wife (A1)
and 39-yr mother (A1B) were considered as suitable donors for four recipients:
19-yr daughter ( blood group B), 50-yr wife (blood group 0), 50-yr husband
(blood group 0) and 21-yr son (blood group A1), respectively. The recipients
serum anti-A1 and anti-B isoagglutinine titer was in range from 1/64 to 1/128
before the procedure. A routine laparoscopic splenectomy was performed in 3
of 4 recipients 38, 42 and 180 days before transplantation. In the 10 days pre-
conditioning period we started with rituximab (375 mgr/m), 4-5 plasmaphereses
to reduce the antibody titer below 1/4, and IvIg (0.5 gr/kgr/bw) one day before
surgery. Standard induction (Daclizumab) and triple drug therapy (CyA, MMF,
steroids) was introduced. The routine 4-5 plasmapheresis was performed in the
first two weeks after transplantation.
Results: Three out of four kidney recipients are doing well 12 months after the
surgery with an avarage serum creatinine of 199 μmol/L and GFR 55 ml/min.
Due to the repeated rejection episodes the second recipeint with unrelated
donor lost the graft after 2 months. The one-month protocol biopsies showed
sub-clinical acute rejections in two recipients and steroid pulse therapy was
introduced. The regularly monitored anti-A1 and anti-B antibody titer in all
recipeints was below 1/8.
Conclusions: The first short-term results despite the loosing of one graft
encourage us to continue with this type of intervention. The authors consider
ABO-incompatible renal transplantation as a safe and promising procedure that
may ameliorate the actual organ shortage in the region.
P129 (281)
THE IMPACT OF DONOR AGE ON EARLY POST-TRANSPLANT
EVENTS AND 1-YEAR GRAFT OUTCOME IN LIVING RELATED KIDNEY
TRANSPLANTATION
J. Masin-Spasovska1, G. Spasovski1, S. Dzikova1, S. Pavlevska1, G. Petrusevska2,
Lj. Lekovski3, Z. Popov3, N. Ivanovski1
1
Department of Nephrology; 2Department of Pathology; 3Department of Urology,
Medical Faculty, University of Skopje, R. Macedonia
Objectives: Donor age was identified as a major factor that unfluences the
short- and long-term outcome after kidney transplantation (Tx). This study
aimed to estimate the relationship between the donor age and (i) early post-
transplant events (delayed graft function-DGF, acute rejection-AR), and (ii) graft
outcome at 1-year after Tx.
475
Int J Artif Organs 2010 ; 33 ( 7): 476
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
Methods: Forty consecutive living related kidney transplant recipients were
included. Biopsies were performed at 1 and 6 months after Tx, and if clinically
indicated. Patients were divided in two groups according to the donor age: G1
(<55 yr, n=16), and G2 (>55 yr, n=24).
Results: The two groups were similar regarding the donor and recipient gender
and body weight, previous time on dialysis, HLA matching, and cyclosporine
target C2 levels. However, the groups differed significantly in the recipient age,
glomerular filtration rate of donated kidney and mean cold ischemic time-CIT
[24.3±5.6 vs. 40.9±5.5 yr (p<0.001); 60.0±17.4 vs. 47.8±14.5 ml/min (p<0.05)
and 3.16±1.1 vs. 4.1±0.6 hours (p<0.001)] for G1 vs. G2, respectively. Moreover,
G2 was characterized by slightly higher percentage of DGF (31% vs. 21%),
subclinical acute rejection (SAR) at 1 and 6 months biopsies (37.5% vs. 25% and
50% vs. 43.8%) and AR (16.7% vs. 12.5%), when compared to G1. In addition,
significant difference in mean serum creatinine and creatinine clearance was
found at 6 months and 1-year after Tx [157.1±39.7 vs. 126.0±45.9 (p<0.05);
52.0±10.8 vs. 72±22.6 (p<0.01) and 181.1±75.6 vs. 138.7±61.1 (p<0.05);
51.4±15.8 vs. 63.9±14.7 (p<0.05)], for G2 vs. G1, respectively.
Conclusions: Our data confirmed that the use of kidneys from older donors
is associated with an incresed risk of DGF and AR episodes, thereby resulting
with a decline in graft function at one year after transplantation. These results
might be explained by the fact that kidneys from older donors may be more
immunogenetic compared to kidneys from younger donors.
P130 (44)
Thyroid cancer in renal transplant recipients
N. Basic-Jukic1, L. Kovac-Bilic2, D. Prgomet2, M. Bilic2, L. Bubic-Filipi1, T. Jukic4,
A. Djanic-Hadzibegovic2, Z. Kastelan3, J. Pasini3, P. Kes1
1
Department of Dialysis; 2Department of Otorhynolaryngology; 3Department
of Urology, Clinical Hospital Centre Zagreb, Croatia; 4Department of Nuclear
Medicine and Oncology, Clinical Hospital Sisters of Mercy, Zagreb, Croatia
Objectives: Malignancies occur more often and behave clinically more
aggressively in kidney transplant recipients than in general population. Papillary
thyroid carcinoma (PTC) is the most common endocrine malignancy with
increasing incidence in general population. We investigated the incidence of PTC
in renal transplant recipients and in patients waiting for renal transplantation.
Methods: From January 1973 to October 2009, 1054 patients received kidney
allograft at our institution. We retrospectively reviewed medical files and from
December 2002 prospectively followed-up kidney transplant patients to identify
cases of PTC.
Results: There were 4 female and one male patients, age ranging from 46 to
59 years (0.47% of transplanted patients). PTC were discovered incidentally
based on ultrasonographic screening for evaluation of parathyroid glands
pathology 1 to 19 years after transplantation in all cases. Patients underwent
total thyroidectomy. The mean size of the largest tumor nodule was 0.72 cm.
Postsurgical radioiodine administration was applied. Immunosuppressive
protocol was modified, with sirolimus introduced instead of the cyclosporine
A in 2 patients. During the mean follow-up period of 12 months all patients
remained disease-free and with a stable graft function. Papillary thyroid
carcinoma was diagnosed in 0.45% of the wait-listed patients, and in 0.0089%
of general population of Croatia.
Conclusions: We discussed the possibility that increased rate of PTC may
merely be a consequence of increased diagnostic work-up of these patients
who are regularly “screened” for parathyroid pathology. Further studies are
needed to solve this dilemma.
P131 (321)
URINARY PROTEINS AS A SURROGATE MARKER FOR GRAFT SURVIVAL
IN MARGINAL LIVING DONOR RENAL TRANSPLANTATION
S. Pavleska, J. Masin, P. Korneti, K. Cakalaroski, P. Kolevski, Z. Popov,
N. Ivanovski
University Clinics of Nephrology, Urology and Institute of Transfusiology, Medical
Faculty, Skopje, R. Macedonia
Objectives: Despite the slightly worse results, the use of marginal living donors
in renal transplantation is a confirmed medical practice all over the world. Due
to the severe organ shortage in the region, we started accepting marginal
living renal donors 20 years ago. The aim of our study is to evaluate the urinary
proteins in the very early period after surgery as a marker of renal lesions and
their predictive value for long-term graft and patient survival.
Methods: Eighty-four renal transplant recipients are included in the study. A
selective proteinuria using SDS-PAGE (sodium dodecyl sulfate polyacrylamide
gel electrophoresis) is performed every other day during the first week, once
weekly in the second, third and forth week after surgery. A total of 40 donors
476 © 2010 Wichtig Editore - ISSN 0391-3988
(I group) were considered as marginal (elderly donors in advanced age, donors
with GFR below 70 ml/min, donors with controlled hypertension, and donors
with single cyst). The results were compared with the younger group (II group)
of donors considered as normal living kidney donors. There is no difference
among the groups concerning immunosuppression, HLA matching, surgical
and preservation procedure, cold and warm ischemia times. The delayed graft
function (DGF), rejection episodes, one, three and five year graft survival are
analyzed.
Results: Eighteen (18) patients in the marginal group of donors showed DGF
in the first week after surgery compared wit 6 in the second. The overall 24 h
proteinuria in the first three weeks was increased in the first group vs. the second,
too (1050 vs. 568.4, 485.4 vs. 333.4 and 225.0 vs. 185.8 mgr/24h, respectively).
SDS-PAGE confirmed a difference among the glomerular (α2 macroglobulin and
albumin) and tubular proteins (α1 microglobuline and α2 microglobuline) with a
predominance in the first group of patients. The one, three and five year graft
survival rates were 90%, 85% and 75% in the first group of pts, compared with
92%, 88% and 80% in the second.
Conclusions: Kidneys from marginal donors are prone to the injuries during
the surgical and preservation procedure. The early selective proteinuria could
be an important marker which, among others, could predict long-term graft
survival. Despite the slightly worse graft survival, the authors consider the use
of marginal living renal donors as suitable. The clinical practice could ameliorate
the organ shortage in the Balkan region.
P132 (323)
NONCOMPLIANCE IN PATIENTS WITH RENAL TRANSPLANTATION - A
CASE REPORT
S. Pavleska-Kuzmanoska, N. Ivanovski, G. Spasovski, M. Masin-Spasovska,
A. Asani, P. Dzekova, G. Nikolov,G. Selim, A. Sikole
University Clinic for Nephrology, Skopje, R. Macedonia
Objectives: In our country experience, about 15-20 patients with end-stage renal
failure per year are treated successfully with kidney transplantation, but some of
kidneys are lost as a consequence of failing to comply to doctor’s instructions.
Noncompliance rates vary from 20 to 50%. A noncompliant patient discontinues
his/her immunosuppressive medications or does not take the medication dose
as it is prescribed. Noncompliance leads to waste of money, time and efforts. It
reduces the benefits of therapy and causes extra costs. Noncompliance is an
important cause of late graft failure and graft loss after renal transplantation.
Methods: In this study we offer a case report and a literature review.
Results: Our patient underwent living unrelated kidney transplantation (LUKTx)
on 15.11.2005 at the age of 31, he had normal recovery, with blood report
nearing normal limits. On the 13th post-operative day serum creatinine level
(sCl) was 131 µmol/L. We followed him up once weekly during the first 3 months
after transplantation and once monthly after 1 year. Blood tests were drawn at
each visit. Acute rejection signs and symptoms are minimal in the late post-
transplantation period thus living nephrologists only with (sCl) and/or cyclosporine
A level as markers of kidney transplant rejection, but such monitoring is difficult
in noncompliant transplant recipients. Noncompliance with immunosuppressive
medications and weight gain were documented months before acute rejection.
Acute rejection episode occurred significantly later (December 2005) and led to
deterioration of graft function and graft lost. Although many studies report that
patients who underwent LUKTx were found to be adherent to their medications,
unfortunately in our case the patient was not.
Conclusion: Noncompliance is multifactorial and should not be ascribed
only as a fault of the patient. Some multidisciplinary measures can be taken:
improved communication between staff and patients, relevant information,
support groups, family support, reducing nonessential drugs.
P133 (150)
EVALUATION OF HEART-TYPE FATTY ACID BINDING PROTEINS AND
TOTAL GLUTATHIONE-S TRANSFERASE LEVELS IN THE PERFUSATE OF
MACHINE PERFUSED KIDNEYS
O.C. Varnav1, C. Moers2, W. van Oeveren1, H.G.D. Leuvenink2, G. Rakhorst1,
R.J. Ploeg2
1
Department of BioMedical Engineering, University Medical Center, Groningen,
The Netherlands; 2Department of Abdominal and Transplantation Surgery,
University Medical Center, Groningen, The Netherlands
Objectives: Heart-type Fatty Acid Binding Proteins (H-FABP) and total
Glutathione-S Transferase (Tgst) are organ injury biomarkers released during
acute ischemia. They could be used to diagnose kidney injury prior to
transplantation.
Methods: We analyzed H-FABP and Tgst in perfusate samples collected at
Int J Artif Organs 2010 ; 33 ( 7): 477
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
10 minutes, 1 hour and end of Machine Perfusion (MP) from 294 Brain Dead
(BD) and 82 Non Heart Beating (NHB) Maastricht category III donor kidneys.
We compared the release of H-FABP and Tgst in the two donor groups and
investigated how it was affected by warm and cold ischemia.
Results: H-FABP and Tgst levels in the NHB group were higher than in the
BD group and correlated with primary warm ischemia: H-FABP levels were
significantly increased already after 10 minutes of MP while Tgst levels at the
end of MP. The correlation between H-FABP and Tgst levels was strong in the
NHB group and moderate in the BD group. The relationship between H-FABP/
Tgst levels and cold ischemia was weak. The levels of both biomarkers did not
change considerably after 4 – 6 hours of MP. In both groups H-FABP was mainly
released during the first hour of MP.
Conclusions: Machine perfused NHB kidneys released higher levels of both
biomarkers in the perfusate. This might be considered as an effect of primary
warm ischemia. Cold ischemia time had little influence on the release H-FABP
and Tgst. H-FABP could be used to detect potentially damaged kidneys within
1 hour of MP, a time point that allows a final check before sending the kidneys
to recipient center.
P134 (226)
URINARY TRACT INFECTIONS IN RENAL-TRANSPLANTed PATIENTS -
OUR EXPERIENCE
S. Mena, V. Dokoska, N. Sela, D. Dokoski
Institute of Nephrology, Struga, R. Macedonia
Objectives: Urinary tract infections (UTI) are the most common form of
bacterial infections occurring in renal transplant recipients. It is very important
to recognize them, in order to avoid further complications. Our goal is to present
our experience with UTI in renal transplant recipients.
Methods: We are using the results of 1-year microbiological analysis
(urinocultures) of 6 patients, taken in their early post-transplant period (up to
6 months). The analyses were repeated on a monthly basis. The urinocultures
were taken from the middle flow of the first morning urine, and cultivated on
highly selective agar. They were performed on highly automated system for
identification and antibiogram - VITEK2 (Bio-Merieux-France).
Results: In 3 patients, we found multiresistant species of E. coli in a number
higher than 10^5/mL. In the detected species of E. coli we diagnosed the
production of extended spectrum beta-lactamases (ESBL) and they were only
sensitive to penems except in one who also produced metalocarbapenemasa
and was only sensitive to fosfomycin. In the other 3 patients we found sterile
urine samples.
Conclusions: Renal transplant patients have asymptomatic UTI due to the
immunosuppressive therapy. Also the transplant has lost its nerve connections,
and therefore UTI may be completely painless. Therefore, it is very important
to promptly diagnose UTI in these patients, because in the worst case
unrecognized infection may lead to grapht loss. The routine urinoculture
is crucial for diagnosing the UTI and the treatment should be based on the
antibiogram.
P135 (75)
TRANSPLANT PATIENTS WITH KIDNEY GRAFT IN CENTRE FOR
HEMODIALYSIS AND NEphROLOGY IN GOSTIVAR – MACEDONIA (1983-
2010)
J. Neskovski, D. Jovceski, B. Aliu, R. Veliu, D. Apostoloski, N. Camili
Centre for Hemodialysis and Nephrology, Gostivar, R. Macedonia
Our Centre for Hemodialysis and Nephrology opened in 1983. The total number
of patients till today (2010) is 362 patients. The number of transplant patients
with kindey graft in a period of 25 years (from 1985), is 28 patients.
Basic DG of recipient-transplant patient are: Glomerulonephritis chr 12,
Nefritis Hereditaria-Alport 4, IPN chr 4, Nefroangiosklerosis 1, Undifferentiated
nephropathy 7. Of the 28 recipients 17 are male, 11 are female. Of the 28
transplantations on kidney, 16 are living-donor transplantations and 12 are
cadaveric transplantations. The number of living donor transplantations
made in Skopje (Macedonia) is 15, but 1 is in Rijeka (Croatia). The number
of cadaveric transplantations made in Skopje is 2, but 10 are made outside
(Russia 1, Turkey 1, India 1, Pakistan 1, Italy 5, Germany 1). The age of patients
who are transplantated (living donor transplantation) recipients (20-30 years -
12, 31-50 years – 4), donors (31-50 years – 6, 51-70 years – 10). Of the 16
patients with living donor transplantation, the donors are: from father – 8, from
mother – 7, from wife – 1 (xenotransplantation in Skopje). The survival of grafts,
living donors transplantation (1-5 years – 6, 5-10 years – 6, 10-20 years – 4),
cadaveric transplantation (1-5 years – 5, 5-10 years – 2, 10-20 years -5). At the
moment patients with living donor transplantation (8 are alive, 4 are dead, 4 are
© 2010 Wichtig Editore - ISSN 0391-3988
brought back to dialysis, cadaveric transplantation (9 are alive, 3 are dead) To
solve the problem of Uremic sick patients who are in progression, is Cadaveric
transplantation.
Artificial liver
P136 (163)
MARS (MOLECULAR ADSORBENT RECIRCULATING SYSTEM) IN LIVER
FAILURE: RESULTS AND PROPOSALS FOR AN IMPROVEMENT OF THE
METHOD
R. Marangoni, G. Bellati, A.Colombo
Dept of Medicine, S. Anna Hospital, Como, Italy
Objectives: Proposals for a future evolution of MARS on the basis of the
reached results.
Methods: 7 patients affected by acute liver failure (ALF) and 93 by acute-on-
chronic liver failure (ACLF), 9 of whom complicated by hepatorenal syndrome
(HS) have been treated with MARS (5 h daily sessions, blood flow 220±20 ml/
min, albumin 150 ml/min). 42 with ACLF lamented severe pruritus and showed
scratching skin lesions. In order to improve metabolites removal, a patient (P)
with high bilirubinaemia (42 mg/dL) after a first session with an albumin standard
circuit (A) underwent a treatment with an albumin circuit with double adsorption
units in parallel (AA).
Results: After a single MARS session bilirubin, bile acids and ammonia fell of
27±7%, 40±5%, 54±14% respectively, with post-treatment rebound variable
in the different subjects. In those affected by HS urea and creatine showed
the same trend as during hemodialysis treatment. After the MARS cycle the
following statistically significant differences were observed: decrease of bilirubin,
bile acids, ammonia, alkaline phosphatase, increase of cholinesterase and
prothrombin activity. AST, ALT, GGTP remained unchanged in patients affected
by ACLF, while significantly decreased in those affected by ALF, all on the way
of recovery. 78 patients affected by ACLF showed an evident improvement of
clinical conditions and liver function, 6 of 9 patients affected by HS reached
a complete recovery of the renal failure and an improvement of liver function.
Pruritus disappeared in all cases after the 3rd MARS treatment. In P bilirubin
clearance calculated on albumin circuit gave the following values in A and AA:
2nd hour of treatment: A: 37.28 ml/min; AA: 73.02 ml/min; 4th hour : A: 28.18 ml/
min; AA: 51.24 ml/min. Percentage bilirubinaemia fall at the end of the session:
A: -28.88%; AA: -52.70%.
Conclusions: MARS has demonstrated to be efficient as replacement therapy
of liver detoxifying function and can be further improved and adjusted for the
patient’s need.
P137 (95)
MICRODIALYSIS - ITS PERSPECTIVE AND ROLE IN EVALUATING THE
EFFICIENCY OF ARTIFICIAL LIVER DEVICES
J. Prazak, E. Laszikova, O. Ryska, E. Koblihova, T. Pantoflicek, M. Ryska
Central Military Hospital, Prague, Czech Republic
Objectives: Acute liver failure is a severe condition with a very unfavorable
prognosis. One of the common complications and limiting factors for the
outcome is the development of intracranial hypertension. The aetiology and
pathogenetic pathways leading to the development and onset of this fatal
complication of acute liver failure is still not completely understood. The
influence of artificial liver devices on the development of cerebral oedema is not
uniquely determined. Microdialysis is a relatively new mini-invasive bed-side
monitoring method, often used in neurosurgery, which informs about the actual
metabolic state of the brain.
Methods: We have searched actual literature using Pub Med for the expressions
Artificial Liver devices, Acute Liver Failure, Microdialysis. We have compared the
results with our own preliminary experimental results.
Results: There are several works using microdialysis in the clinical monitoring
of brain damage during ALF, but only few experimental works on ALF treated
by artificial liver devices using the microdialysis technique in the monitoring.
According to our initial experience with microdialysis technique in the field of
experimental ALF treated by FPSA eliminating system, this monitoring technique
seems to reflect soon the positive influence of this artificial liver device on brain
metabolism.
Conclusions: Microdialysis, as a new method of tissue metabolism monitoring,
seems to be very perspective in the area of ALF, but its place and role in the
evaluation of the efficacy of artificial liver devices requires further experimental
and clinical studies.
477
Int J Artif Organs 2010 ; 33 ( 7): 478
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P138 (100)
Granulocyte Colony-Stimulating Factor (G-CSF) Usage for
Liver Regeneration In the Condition of Toxic Hepatitis
V. Zaporozhan, O. Kholodkova, D. Pykhtyeyev, A. Shcherbatyuk
Odessa State Medical University, Odessa, Ukraine
Objectives: We studied G-CSF influence on the state of liver in toxic influence
condition.
Methods: I group of experimental animals were injected adriblastin (10 mg/kg).
II group of animals were injected G-CSF (100 mkg/kg) 10 days after adriblastin
injection.
Results: Signs of nonspecific reactive hepatitis, namely disorder of beam
structure, expansion of sinusoids, inflammatory infiltrations of portal tracts
and parenchyma of liver, granular dystrophy of hepatocytes (HC) decrease of
glycogen in cytoplasm were observed in the I group 20 days after adriblastin
injection. Specific density (SD) of connective tissue rose 18%, SD of binuclear
HC decreased 1.6 times, SD of HC with picnotic nuclei rose 10.8 times
comparatively to the control. Alanine aminotransferase activity rose 3.8 times,
aspartate aminotransferase 1.9 times, alkaline phosphatase 1.3 times, total
bilirubin 2.15 times comparatively to the control. A considerable decrease
of pathological changes in liver in the II group of animals was observed. SD
of connective tissue rose 12%, SD of binuclear HC decreased 1.3 times
comparatively to the control. SD of HC with pyknotic nuclei was 5.7 times higher
than in the control. The amount of glycogen in cytoplasm of HC was restored.
Activity of hepatic enzymes was approximately similar to the control.
Conclusions: The protective action of G-CSF can be associated with
prostaglandin mediated reaction, therefore synthesis of proteins is intensified and
with intensification of SC leaving their depot. G-CSF is a potential agent for the
morphofunctional state of hepatic tissue restoration in toxic hepatitis condition.
P139 (113)
IN VITRO CULTURE OF PRIMARY ISOLATED HUMAN LIVER CELLS
A. Smietanka1, A.K. Strzalkowski1, K. Dudek2, J. Kawiak1, K. Pluta1
1
Laboratory of Tissue Engineering, Nalecz Institute of Biocybernetics and
Biomedical Engineering, PAS, Warsaw, Poland; 2Department and Clinic of General
Surgery and Liver Diseases, Warsaw Medical University, Warsaw, Poland
Objectives: The aim of the presented study was to characterize primary isolated
human liver cells during long-term in vitro culture to verify the effect of isolation
method elaborated in our laboratory. Basic metabolic functions were measured
and flow cytometry was conducted to characterize cells freshly after isolation
and during culture.
Methods: Primary isolated human liver cells were cultured in 12-well culture
plates on polystyrene surface untreated or coated with collagen type I or
MatriGel, in William’s Medium E supplemented with 10% inactivated FBS, 100
units/mL penicillin, 100 µg/mL streptomycin, 1% MEM NEAA solution, 10 Mm
HEPES (humidified atmosphere with 5% CO2, 37ºC).
Results: Isolated cells indicated good viability, growth and proliferation rates
over one month of culture. However, liver specific functions (albumin production,
morphology, cell polarization, glycogen accumulation, urea production) either
did not appear or declined during first week of culture on collagen type I. On the
other hand, culturing liver cells on MatriGel as a growth surface enabled albumin
production up to 3-4 weeks. Cells morphology became similar to fibroblasts-like
one but with numerous processes protruded from all cells.
Conclusions: In primary isolated human liver cells hepatocyte specific functions
have been declining during in vitro culture but both growth and proliferation
rates of liver cells in culture were unaltered. Therefore our isolation method
provides a good material for hepatocyte differentiation studies.
Acknowledgements: This work was partially supported by MNS-DIAG,
POIG.01.03.01-00-014/08-01.
P140 (99)
ISOLATION AND CHARACTERIzATION OF HUMAN LIVER CELLS
A. Smietanka-Grzeczkowicz1, A. Kinasiewicz2, K. Dudek2, A.K. Strzalkowski1,
J. Kawiak1,3, K. Pluta1
1
Nalecz Institute of Biocybernetics and Biomedical Engineering, PAS; 2Medical
University of Warsaw; 3Medical Center of Postgraduate Education, Warsaw, Poland
Objectives: Bioartificial Liver as well as liver cells transplantation is the future
alternative to organ transplantation. Unfortunately, the quantity of human
hepatocytes available from isolation is rather small. Additionally, during culturing
liver cells gradually lose their specific functions, such as albumin production.
The aim of our experiments was to compare different methods of human liver
478 © 2010 Wichtig Editore - ISSN 0391-3988
cells preparation by characterization of the isolated and cultured cells.
Methods: Human liver samples were obtained from partial hepatectomy. In our
experiments we used either collagenase I or IV. Cells were isolated using different
approaches: one method was based on the classical two-step collagenase perfusion
technique; in the other – tissue was minced and incubated in 37°C in collagenase
solution. The maceration was performed either in water bath with moderate agitation or in
the beaker placed on magnetic stirrer. Cells were cultured on surfaces previously coated
with either collagen type I or Matrigel in a William's E medium with 10% FBS. Cultures
were evaluated by light microscopy, fluorescence microscopy, and ELISA tests.
Results: Regardless of the isolation method used, we obtained similar
quantities of liver cells. Microscopical observations of cell cultures derived using
these methods showed no differences in their appearance. DAPI and Phalloidin
staining disclosed the presence of different cell types, however most cells had
fibroblasts-like morphology. The staining did not show typical for liver and C3A
cell line structures, bile canaliculi. Moreover, in all cases, ELISA tests detected
decreasing albumin production.
Conclusions: Liver cells isolation can be carried out using different techniques.
Moreover, collagenase I and IV digested liver tissue with similar efficacy.
However, cultured cells isolated with presented methods were gradually losing
their liver functions and proper cultivation conditions must be established to
overcome this limitation.
Acknowledgements: This work was partially supported by MNS-DIAG,
POIG.01.03.01-00-014/08-01.
P141 (114)
EFFECT OF ONCOSTATIN M ON LIVER CELLS IN IN VITRO CULTURE
A.K. Strzalkowski1, A. Smietanka1, K. Dudek2, K. Pluta1
1
Laboratory of Tissue Engineering, Nalecz Institute of Biocybernetics and
Biomedical Engineering, PAS, Warsaw, Poland; 2Department and Clinic of
General Surgery and Liver Diseases, Warsaw Medical University, Poland
Objectives: Oncostatin M (OSM) was demonstrated to regulate cell proliferation
and maturation in fetal liver, as well as progression of hepatic development in
postnatal liver. Dexamethasone (Dex), a synthetic glucocorticoid, was shown to
modulate OSM effect. The aim of the presented study was to reveal the effect
of OSM and Dex on basic metabolic functions of both: C3A cells derived from
human hepatoma and primary isolated human liver cells.
Methods: Primary isolated human liver cells were cultured in 12-well culture
plates on surface coated with collagen type I, in supplemented William’s Medium
E. C3A cells were cultured in uncoated 24-well culture plates, in supplemented
DMEM. In experimental groups OSM and Dex were added at concentrations of
50ng/mL and 1x10-6M, respectively.
Results: Addition of OSM and Dex caused decrease of C3A cells viability.
OSM added either separately or together with Dex strongly inhibited albumin
production of C3A cells (twofold comparing to the control). Dex added either
alone or together with OSM modified urea metabolism in both C3A cells and
primary isolated human liver cells leading to decreased urea concentration
in culture medium. Presence of OSM together with Dex reduced glucose
consumption of both C3A cells and primary isolated human liver cells. In
primary isolated human liver cells cultured on collagen type I, OSM slightly
slackened the decline rate of albumin production when compared to untreated
control. Interestingly, neither addition of OSM alone nor in combination with Dex
influenced bileduct-like structures formation.
Conclusions: OSM exerted different effect on mature C3A hepatoma cells and
on adult primary isolated human liver cells compared with what was earlier
reported for fetal liver cells. Both former cell types were sensitive to cytokine
stimulation, yet contrary to other reports, our studies showed that OSM added
alone or together with Dex did not enhance mature hepatocyte functions in
in vitro culture.
Acknowledgements: This work was partially supported by MNS-DIAG,
POIG.01.03.01-00-014/08-01.
Polymeric Biomaterials
P142 (52)
EVALUATION OF IN VITRO BIOCOMPATIBILITY OF HYDROGELS AS
VITREOUS BODY SUBSTITUTES
S. Lamponi1, G. Leone1, M. Consumi1, G. Greco2, A. Magnani1
1
Department of Pure and Applied Medicinal Chemistry, University of Siena,
Siena, Italy; 2Casa di cura Rugani, loc. Monatarioso, Siena, Italy
A new method, based on the use of a non toxic substance as cross-linker
Int J Artif Organs 2010 ; 33 ( 7): 479
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
agent, trisodium trimetaphosphate (STMP), to crosslink PVA was proposed.
Hydrogels with the following molar ratios between STMP and PVA were realized:
1:4, 1:6, 1:8. The hydrogels were characterized by Infrared Spectroscopy and
rheological analysis. On the basis of rheological analysis, light transmittance
and water content measurements, the most suitable hydrogel as vitreous
substitute was the STMP/PVA 1:8. The 1:8 sample was further characterized in
terms of thixotropic behavior, injectability and permeability. The STMP/PVA 1:8
showed good injectability with a negligible change of its rheological properties.
Moreover, the diffusion coefficient (DC) of a model molecule (phenylalanine)
through the hydrogel was found to be very similar to its DC in water.
As the synthetic injectable hydrogels must have a very high biocompatibility,
a fundamental aspect in their characterization is the knowledge of the effects
of their interactions with cells. The evaluation of the biocompatibility of the
three hydrogels previously synthesized, in terms of their in vitro interaction with
cultures of mouse fibroblasts NIH3T3 and primary human Endothelial Cells
(HMVECad) was performed. Cytotoxicity of hydrogels was evaluated by cell
density and proliferation analysis through the measurements of the rate of cell
viability with WST-1 assay, and by morphological and morphometric analysis
using light and scanning electron microscopy (SEM), respectively. Moreover, cell
adhesion and growth directly on the hydrogels surface was evaluated by SEM
and correlated to the amount of adsorbed proteins. At last, in vitro adhesion of
human lens cells to hydrogels was studied.
The results obtained demonstrated that all the STMP/PVA hydrogels properties
make them suitable as vitreous substitutes. Among them, the 1:8 sample,
showing the best behavior in terms of biocompatibily, was the most suitable
candidate.
P143 (35)
THERMORESPONSIVE HEPARIN BIOCONJUGATE AS A NOVEL AQUEOUS
ANTITHROMBOGENIC COATING MATERIAL
Y. Nakayama1,2, S. Yamaoka1,3, Y. Nemoto4, A. Borovkov1,2, K. Uchida3
1
Department of Bioengineering, Advanced Medical Engineering Center,
National Cardiovascular Center Research Institute, Osaka, Japan; 2Division of
Biotechnology and Macromolecular Chemistry, Faculty of Engineering, Hokkaido
University, Sapporo, Japan; 3Department of Materials Chemistry, Faculty of
Science and Technology Ryukoku University, Shiga, Japan; 4Chemical products
Divison, Development Department, Brigestone Corporation, Yokohama, Japan
Objectives: As a novel thermoresponsive aqueous antithrombogenic coating
material, a heparin bioconjugate with poly(N,N-dimethylaminoethyl methacrylate)
(PDMAEMA), which has both thermoresponsive and cationic characters, was
developed to reduce the thrombogenic potential of natural occurrence or tissue-
engineered tissues, or polymeric materials for cardiovascular implantation.
Methods and Results: PDMAEMA with 6-branched star shape and Mn of ca.
24 kDa was prepared by initiator-transfer agent-terminator (iniferter)-based living
radical photopolymerization from hexakis (N,N-diethyldithiocarbamylmethyl)
benzene. Bioconjugation of heparin with PDMAEMA occurred immediately upon
simple mixing of both aqueous solutions to form particles with several hundred
nanometers in diameter. The particles were very stable due to completely
prevention of hydrolysis of PDMAEMA in bioconjugated form. Since the lower
critical solution temperature of the heparin bioconjugate was approximately
34 degree, it could be coated from an aqueous solution at room temperature.
The excellent adsorptivity and high durability of the coating above 37 degree
was demonstrated on polyethylene and silicone films by surface chemical
compositional analysis, and on connective tissue sheets by heparin staining.
Blood coagulation was significantly prevented on the heparin bioconjugate-
coated surfaces.
Conclusions: The thermoresponsive bioconjugate developed therefore appeared
to satisfy the initial requirements for a biocompatible aqueous coating material.
P144 (105)
Endothelialization potential of titanium-coated
Polyurethanes – Biofunctionalization for medical
applications
J. Li1, S. Riescher1, S. Schopka1, D. Wehner2, T. Schmid2, B. Girndt3,
H. Zimmermann3, K. Stadtherr4, C. Schmid1, K. Lehle1
1
Department of Cardiothoracic Surgery, University Medical Center, Regensburg,
Germany; 2German Aerospace Center, Institute of Robotics and Mechatronics
Robotik and Mechatronik Robotic Systems, Oberpfaffenhofen-Wessling,
Germany; 3GfE Medizintechnik GmbH, Nürnberg, Germany; 4Institute for
Medical Microbiology and Hygiene, University of Regensburg, Germany
Objectives: The aim of this study was to improve the anti-thrombogeneity of
poly(ether)urethanes (PU) for medical applications such as pump chambers of
© 2010 Wichtig Editore - ISSN 0391-3988
implantable ventricular assist devices (VAD).
Methods: Different types of commercially available PU, the main component of
the pump chambers, were examined with regard to their mechanical flexibility.
Cultures of human endothelial cells (EC) (n=8) were applied to evaluate the
in vitro cytotoxicity and thrombogenicity of the raw material and of a surface
modified PU coated with a covalent bound titaniumcarboxonitride. Tissue-
cultured polystyrole (TCP) was used as a reference.
Results: Durability and flexibility of medical degrade PU was confirmed.
EC adhered onto the surface of uncoated and titanium-coated PU, but EC
proliferated only after seeding onto titanium-coated PU. Mitochondrial activity
of cells adhered to titanium-coated surfaces was found to be similar to TCP
(p<0.05). Coverage of surfaces such as uncoated and titanium-coated PU and
TCP with a monolayer of EC prevented the adhesion of isolated thrombocytes
(2 to 5fold) and mononuclear cells (1.5 to 3fold).
Conclusions: These experiments indicate that medical degraded PU impeded
EC seeding. Implementation of a covalent bound titanium-layer onto the PU
surfaces allows endothelialization and reduces cytotoxicity and thrombogenicity
of PU without affecting the materials flexibility. Covalent bound titanium-coating
of polymeric surfaces might be useful for tissue engineering.
P145 (337)
BIOCOMPATIBILITY OF ELECTROSPUN POLYURETHANE PATCHES
H. Bergmeister2,4, C. Grasl1,2, C. Schreiber2, I. Walter2,5, R. Plasenzotti2,4,
H. Schima1,2
1
Center for Biomedical Engineering and Physics, Med. Univ. Vienna, Austria;
2
LBC for Cardiovascular Research, Austria; 4Divison of Biomedical Research,
Med. Univ. Vienna, Austria; 5Department of Pathobiology, Veterinary University,
Vienna, Austria
Objectives: Three-dimensional synthetic polyurethane scaffolds serve as
an excellent framework for cell adhesion, proliferation and differentiation. We
investigated the biocompatibility of electrospun nanofiber mesh scaffolds with
commercially available PTFE patches in a rat model.
Methods: Scaffolds (10x10 mm) of electrospun polyurethane (n=40) or PTFE
(n=40) were implanted subcutaneously in rats and retrieved after 1 week
or 1, 3 or 6 months. Specimens were evaluated by conventional histology,
immunohistochemistry and transmission electron microscopy.
Results: Within 1 month polyurethane scaffolds showed a significant lower
immigration of inflammatory cells (CD3+, CD20+, MPO+, ED1+cells) than PTFE
implants. Giant cell reaction was not detectable. Electrospun implants revealed
ingrowth of myofibroblasts. After 6 months' implantation electrospun scaffolds
looked nearly bioinert, whereas PTFE implants showed a strong granulomatous
foreign body reaction.
Conclusions: Electrospun polyurethane patches induce less inflammatory
reaction compared with PTFE patches and seem to be more biocompatible
especially in long-term applications.
P146 (328)
Composites of Supramolecular PCL and Supramolecularly
Surface Modified Nanoapatite Particles for Tissue
Engineering
P. Shokrollahi, H. Mirzadeh, M. Mehmanchi
Iran Polymer and Petrochemical Institute, Tehran, Iran
Aiming to optimize the mechanical properties and the bioactivity of PCL for
tissue engineering applications, its composites with bioactive ceramics
have been prepared and examined in vitro/in vivo. Dealing with dynamic
interactions between the living cells and the ECM, bioresponsiveness of
synthetic ECMs becomes crucially important. In the search for novel materials
with the ability to adopt their biofunctionality according to the requirements
of living cells, self assembling peptide architecture and hydrogen bonded
supramolecular polymers have been designed and studied for their bioactivity.
Supramolecular polycaprolactone based on quadruple hydrogen bond forming
ureidopyrimidinone(Upy) moiety holds promise as a favourable biomaterial for
tissue regeneration.
We show that despite the dynamic nature of hydrogen-bonded systems,
bioactive composites can be prepared from supramolecular polycaprolactone
and bio-ceramic hydroxyapatite. Aiming to increase the interfacial interaction at
the organic/inorganic interface through hydrogen bond array formation, Upy-
groups were grafted on the surface of hydroxyapatite (HapUPy) and composites
of hydrogen bonded PCL with both unmodified (Hap, 10, 15 and 20 wt%
inorganic) and Upy functionalized hydroxyapatite (HapUPy, 10, 15 and 20 wt%)
were prepared.
DSC results showed that the Tg was affected by the presence of the inorganic
479
Int J Artif Organs 2010 ; 33 ( 7): 480
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
species suggesting that there is an interaction between organic/inorganic
phases. DSC data also confirmed that the interaction is stronger in case of Upy-
modified hydroxyapatite. Mechanical testing showed that all studied composites
have a higher Young’s modulus compared to the pristine PCL1250(Upy)2, which
was also confirmed by dynamic mechanical measurements. Mechanical and
dynamic mechanical measurements revealed that surface modification of Hap
particles with Upy functionality enhances the mechanical properties and load
bearing character of the composite. Scanning electron microscopy investigation
revealed that the Upy-modified particles distributed more uniformly throughout
the composite. Data from mechanical, dynamic mechanical and microscopy
analysis show that dynamic composites of PCL(Upy)2/HapUPy demonstrate
superior mechanical and dynamic mechanical properties compared to the
conventional composite PCL1250(Upy)2/Hap (at similar inorganic amounts).
P147 (104)
Effect of Nanostructure and Composition of PLGA-Gelatin
Electrospun Nanofibrous Scaffolds on Cell Behavior
S.M. Saeed, M. Zandi, H. Mirzadeh
Iran Polymer & Petrochemical Institute, Iran
Objectives: The purpose of this study is to investigate the cell behavior on
PLGA and PLGA/Gelatin hybrid scaffolds. In this study, nanofibrous scaffolds
are fabricated using the electrospinning method. Electrospinning of polymer
blends dissolved in different or the same solvents and electrospinning of the
mixture of natural and synthetic polymers were studied in order to improve the
properties of synthetic and natural polymers, which have leads to creation of
new types of scaffolds with good biocompatibility and improved mechanical
and physical/chemical properties. Since fiber structure and morphology are
important parameters in cell behavior, this study investigates the effect of
morphology and nanostructure of PLGA and PLGA/Gelatin scaffolds on cell
behavior and cell seeding results.
Materials and Methods: The materials used in this study include gelatin,
Gelita; carbodiimide derivative, Merck; PLGA Boehringer; HFIP, Merck; PLGA
and PLGA/Gelatin are fabricated through electrospinning technique. Fabricated
PLGA and PLGA/Gelatin scaffolds are coated by gelatin and then crosslinked.
Finally, these scaffolds are dried in oven under vacuum conditions, at 37°C, for
48 hours.
Results: The SEM micrographs show that in electrospinning process, fine fibers
can be obtained by optimizing of different parameters such as tip-to-collector
distance, voltage and feeding rate as well as polymer composition. According to
our results, the attachment and the proliferation behavior of the cells on PLGA/
gelatin hybrid scaffolds show better results comparing to PLGA scaffolds.
According to observations in this study, novel nanofibrous scaffolds that are
made of PLGA and gelatin reveal quite appropriate and uniform cell seeding.
Conclusions: Since all tissues in the body have the same structure as
nanofibrous structure, the scaffolds fabricated by nanofibers are one of the best
candidate in tissue engineering. As gelatin is added to the scaffold, we observe
that cell behavior is being improved. We concluded that the scaffolds fabricated
in this study enjoy high potentials as desirable scaffolds in tissue engineering.
P148 (127)
APPLICATION OF FUNCTIONAL hemo-compatibility COATINGS FOR
IMPLANTABLE DEVICES OF ARTIFICIAL HEART
V.V. Morozov, L.V. Belyaev, A.V. Zhdanov
Vladimir State University, Vladimir, Russian Federation
Objectives: Putting monolayer, multilayer coatings, which have simple or strong
chemical compositions, by different methods is one of the promising areas
on creating biomedical materials with high mechanical properties, bio- and
hemocompatibility measures, also with small weight.
Methods: At the Vladimir State University the scientists carry out the research
by putting hemocompatibility coatings to artificial ventricles of heart, which are
made by foundry of thermoplastic po-lyurethane by vitur PFTM-0533-90 grade
by method of physical vapour deposition (PVD) and physical laser deposition
(PLD) in the evacuated vessel. Observed researches were making at the Russian
equipment names Unicoat 600 SL+ and fibre optic ytterbium laser with Q switching.
Exam of getting coatings was carried out with using a sonden nanolaboratory
Integra Aura and the electron scanning microscope Qanta 200 3D.
Results: Samples were obtained by the different techniques of putting coatings,
researched thicknesses and structure of them, surface’s topology, which
generated after putting coating, adhesion of the layers to surface.
Conclusions: New techniques were developed to put nanostructured coating of
Ti, TiN, TiCN to composite surface of artificial ventricles of heart by the methods
mentioned above.
480 © 2010 Wichtig Editore - ISSN 0391-3988
P149 (134)
HEMOCOMPATIBILITY TESTS ON MATERIALS FOR A MULTI-TACTILE-
SENSOR CONCEPT
J. Arens¹, P. De Brouwer¹, I. Mager1, C. Brücker², M. Schäfers³, P. Jacobs³,
T. Schmitz-Rode¹, U. Steinseifer¹
1
Inst. for Applied Medical Engineering, RWTH Aachen University, Germany;
2
Inst. Mechanics and Fluid Dynamics, TU Bergakademie Freiberg, Germany;
3
Fraunhofer Inst. for Laser Technology, RWTH Aachen University, Germany
In order to develop a multi-tactile sensor for the measurement of the inner
geometry of human blood vessels, surfaces with microhairs were produced from
Polydimethylsiloxan (PDMS). Due to the use inside blood vessels these surfaces
with microhairs (d = 100 µm, l = 200-1000 µm) need to be hemocompatible.
The planned duration of examination with this sensor is up to 20 min inside
the blood vessels. Though, a short-term dynamic hemocompatibility test setup
was needed.
For the test setup flat probes with microhairs with a standardized base area of
30 x 30 mm² were used. Number of hairs was varied from 1200 to 2400 and
3600, but the distance of hairs was constant (0.5 mm). The probes were put
into a flow chamber (dimensions: w=30 mm, h=1 mm, l=150 mm). Comparative
tests were undertaken in three identical test circuits comparing two probes with
haired surfaces and one probe without hairs. Test duration was 20 min. The
circuits were primed with physiological NaCl solution. Test fluid was heparinized
porcine blood (ACT > 130 sec). Blood temperature was kept to 37 °C ± 1 °C by
placing the whole setup inside a climate chamber. Flow through the chambers
was set to 500 ml/min by use of roller pumps. Samples were collected at 0, 5,
10, 15, and 20 min. Rate of hemolysis is specified by the quantity of plasma-
free hemoglobin. Adhesion of cells to the hairs will be examined by scanning
electron microscopy (SEM).
The priming of the flow chambers to wet all surfaces and to eliminate air
bubbles showed that the hydrophobe PDMS surfaces (hairs) need extra
attention regarding the de-airing. Analyses of blood damage and the SEM are
presented.
A test setup with test conditions according to heart catheter examinations could
be successfully implemented. First results show, that the de-airing of the sensor
will be a challenge to implement in the insertion instrument.
Biomaterials
P150 (278)
SODIUM DODECYL SULPHATE THE IN PROCESSING OF BOVINE
PERICARDIUM
A. Turek1, B. Cwalina2, A. Marcinkowski3, B. Trzebicka3, Z. Dzierżewicz1
1
Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland;
2
Environmental Biotechnology Department, Silesian University of Technology,
Gliwice, Poland; 3Centre of Polymer and Carbon Materials, Polish Academy of
Sciences, Zabrze, Poland
Objectives: Sodium dodecyl sulphate (SDS) is an anionic surfactant useful
to lyse cells during the processing of tissues. This reagent is effective in
removing cells from allogeneic and xenogeneic tissues used as scaffolds for
tissue engineering. However, SDS may also influence the elements structure
in the tissue. The aim of this work was to determine the effect of SDS on the
nanostructure of connective fibers in bovine pericardium (BP).
Methods: BP was obtained from the local abattoir and transported to the
laboratory. Fatty tissue and sections with heavy vasculature were gently
removed. Tissue samples were treated (for 48 hours) with a solution containing
0.3% of SDS and 0.09% of sodium chloride (NaCl). The tissue nanostructure
elements were studied under an atomic force microscope (AFM) MultiMode 3
(di-Veeco, CA), working in the tapping mode.
Results: Native tissue showed D-spacing in connective tissue fibers, with
the distance of 68-78 nm being typical for collagen type I. The surface of
the SDS-treated tissue was free from the debris of extracellular matrix. The
solution containing SDS and NaCl induced changes in the D-banding pattern.
The collagen-periodicity in the SDS-treated tissues increased to values of
approximately 96 nm. This effect points out changes in tissue cross-linking
and other interactions. It is known that SDS may disrupt the hydrogen bonds
in proteins. However, no significant disintegration of fibers in the tissue was
observed in our experiment. SDS-treated tissue was correctly preserved and
maintained morphological features characteristic for the native tissue.
Conclusions: Results of AFM-studies showed that the nanostructure of SDS-
treated BP may be satisfactory for the formation of bio-scaffolds.
Int J Artif Organs 2010 ; 33 ( 7): 481
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P151 (279)
GLUTARALDEHYDE AND TANNIC ACID IN THE MODIFICATION OF
PORCINE PERICARDIUM
A. Turek1, B. Cwalina2, A. Marcinkowski3, B. Trzebicka3, Z. Dzierżewicz1
1
Department of Biopharmacy, Medical University of Silesia, Sosnowiec, Poland;
2
Environmental Biotechnology Department, Silesian University of Technology,
Gliwice, Poland; 3Centre of Polymer and Carbon Materials, Polish Academy of
Sciences, Zabrze, Poland
Objectives: Nowadays, glutaraldehyde (GA) is the most often used cross-
linking agent applied in the stabilization of collagen-rich tissues for obtaining
bioprosthetic heart valves. The significant disadvantages of GA-stabilized
tissues are calcification and cytotoxity of the tissue, and premature degradation
of elastin. A partial elimination of these drawbacks may be achieved by tissue
stabilization in the mixture containing GA and tannic acid (TA). The aim of this
work was to determine the micro- and nanostructure of porcine pericardium
(PP) stabilized by GA and TA.
Methods: PP was obtained from the local abattoir and subsequently transported
to the laboratory. Fatty tissue and sections with heavy vasculature were gently
removed from prepared samples. PP was treated with solutions containing GA
and/or TA in combinations: (i) 0.2% of TA, (ii) 2% of TA, (iii) 0.2% of GA and
0.2% of TA, (iv) 0.2% of GA and 2% of TA, in the course of 4 hours. The tissue’s
nanostructure was studied under an atomic force microscope (AFM) MultiMode
3 (di-Veeco, CA), working in the tapping-mode. The PP microstructure
was examined in optical microscopy, at a magnification of 200x. The tissue
specimens were stained with hematoxylin and erythrosine.
Results: Different morphological features in micro- and nanostructures in PP
after stabilization with GA and TA were revealed. Optical microscopy showed
a prevented native structure. However, AFM imaging of GA- and TA-treated
tissues showed significant morphological changes. Cross-linking processes led
to changes in the periodicity of collagen fibers, making them irregular. Moreover,
broadening of collagen fibers was observed.
Conclusions: GA and TA act synergistically in tissue stabilization. The
intensification of morphological changes was correlated with an increased
concentration of the reagents.
P152 (140)
FREEZE-DRIED AND IRRADIATED BOVINE PERICARDIUM MODIFIED
WITH SILK FIBROIN AND CHITOSAN: CALCIFICATION RESULTS
R. Polak1, R.F. Weska3, A.C.D. Rodas2, M.M. Beppu3, O.Z. Higa2, R.N.M.
Pitombo1
1
Department of Biochemical and Pharmaceutical Technology, School of
Pharmaceutical Sciences, University of São Paulo, USP, São Paulo-SP, Brazil;
2
Biotechnology Center, Energy and Nuclear Research Institute, IPEN – CNEN/
SP, São Paulo-SP, Brazil; 3School of Chemical Engineering, University of
Campinas, Campinas-SP, Brazil
Objectives: The aim of this study was to investigate the in vitro calcification
behavior of the modified samples of bovine pericardium (BP) by irradiation
and with chitosan (CHIT), silk fibroin (SF) and their mixtures (1:1, 1:3 and 3:1).
These modifications were performed in order to achieve potential membranes
to be used as biomaterials, such as in bioprosthesis confection. Furthermore,
previous biofunctionality results showed that the samples modified with SF/
CHIT (all ratios) and irradiation favored the adhesion and growth of endothelial
cells throughout the tissue.
Methods: After the modifications, half of the samples were irradiated with 25kGy
at 4.67kGy/s (determined in previous work). Calcification test was carried out
using a simulated body fluid (SBF) solution in two concentrations 1× and 1.5×,
in order to accelerate the calcification process. Samples of 4cm2 were soaked
in 50Ml of 1.5×SBF solution at 36.5°C under agitation for 7 days. SBF solution
was changed every 48h (1×, 1.5×, 1.5×). Then, the samples were rinsed with
ultrapure water to remove excess of salts on their surface and then freeze-dried
for Scanning Electron Microscopy and Energy-dispersive X-ray spectroscopy
analyses.
Results: Calcification results showed that all samples induced calcification.
However, all samples showed the relation Ca/P smaller then hydroxyapatite’s.
Conclusions: Although the samples modified by CHIT and SF mixtures (all
ratios) and irradiated presented calcification, they also presented affinity to
endothelial cells. This endothelial cell layer could help to keep valve integrity and
furthermore, improve its mechanical properties and even avoid its pathological
calcification.
© 2010 Wichtig Editore - ISSN 0391-3988
P153 (139)
STRUCTURAL CHARACTERIZATION AND IN VITRO ENDOTHELIZATION
STUDY OF FREEZE-DRIED BOVINE PERICARDIUM MEMBRANES
V. Tattini Jr1, A.C.D. Rodas2, M.J.S. Maizato4, A.A. Leirner4, M.M. Beppu3,
O.Z. Higa2, B. Polakiewicz1, R.N.M. Pitombo1
1
School of Pharmaceutical Sciences, University of São Paulo, USP, São Paulo-
SP, Brazil; 2Energy and Nuclear Research Institute, São Paulo-SP, Brazil; 3School
of Chemical Engineering, University of Campinas, Campinas-SP, Brazil; 4Heart
Institute-Medical School, University of São Paulo, São Paulo, Brazil
Objectives: To investigate the influence of the 2,2’-[phenethylimino dimethylene]
bisoxirane CAS [1207734-60-8]P cross-linking on bovine pericardium secondary
structure compared to native and glutaraldehyde cross-linked. The collagen
cross-linked freeze-dried bovine pericardium membranes were tested in their
biocompatibility with cytotoxicity assay and endothelial cell growth. These
modifications were performed in order to achieve potential membranes to be
used as bioprosthesis confection.
Methods: Freeze-drying was used as a mediator in the process of the
cross-linking and all pericardium samples were freeze-dried before chemical
modifications. The epoxide was synthesized, using a method described in a
previous paper. Pericardium membranes micrographies were obtained by
Scanning Electron Microscopy. The secondary structures of native and freeze-
dried tissues were determined by Raman spectroscopy. Membranes without
cytotoxicity were analyzed by confocal microscopy.
Results: Bovine pericardium tissue glutaraldehyde cross-linked appeared
more compacted than the bovine pericardium epoxide cross-linked membrane.
Freeze dried bovine pericardium epoxide cross-linked, presented better
interaction with cells in comparison with the freeze dried bovine pericardium
glutaraldehyde cross-linked, in which most of the cells showed non-functional.
Conclusions: Freeze-dried bovine pericardium 2,2’-[phenethyliminodimethylene]
bisoxirane cross-linked membranes could be used as an alternative to
glutaraldehyde cross-linked pericardium bioprostheses. Probably the collagen
secondary structure preservation favored the compatibility for endothelial cells
growth.
P154 (203)
HYDRODYNAMIC AND STRUCTURAL CHARACTERIZATION OF
TAURODEOXYCHOLATE PORCINE HEART VALVES: A NOVEL METHOD FOR
THE PRODUCTION OF TISSUE GUIDED REGENERATION SCAFFOLDS
E. Buratto, A. Gandaglia, F. Naso, C. D’Agostino, C. Dal Lin, T. Bottio, M. Spina,
G. Gerosa
University of Padua, Padua, Italy
Objectives: The aim of this study was to investigate the effects of previously
untested detergent taurodeoxycholate, as a novel decellularizing agent for
biological heart valves, both from a hydrodynamic and a structural perspective.
Decellularization quality, maintenance of structure and repopulation potential
were all investigated.
Methods: Fresh porcine aortic roots were treated using a combination of
hypotonic and hypertonic solutions with the detergents Triton X 100 and
Taurodeoxycholate (TRI-TDOC method) followed by nucleic acid digestion with
a non-specific endonuclease. Structure of the aortic cusps, walls and sinuses
was investigated by transmission electron microscopy and by means of classic
histology, immunohistochemistry and fluorescence methods. Additionally,
alteration of hydrodynamic behavior was investigated by testing systolic and
diastolic performance of the same valves pre-and post-decellularization in a
Sheffield Pulse duplicator.
Results: TRI-TDOC protocol has the potential to create a porous scaffold,
preserving proteoglycans, whilst completely removing cells and their
components. Basement membrane components, Collagen IV and Fibronectin
especially, were largely intact. Hydrodynamic performance demonstrated
significantly increased transvalvular gradients (p < 0.5) and regurgitant volumes
(p < 0.5) post-treatment.
Conclusions: The study demonstrates that taurodeoxycholate is an effective
decellularizing agent, with a significantly different action to previously published
methods. Further investigation of the scaffold in a dynamic bioreactor should be
carried out in order to verify its potential to be repopulated under physiological
conditions.
481
Int J Artif Organs 2010 ; 33 ( 7): 482
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P155 (198)
TISSUE ENGINEERING: STANDARDIZED FABRICATION OF HEART VALVES
UNDER GMP CONDITIONS
C. Lueders, R. Hetzer
Deutsches Herzzentrum, Berlin, Germany
Objectives: Tissue engineering may be an alternative means of reconstruction
of organs and organ structures. The fabrication of tissue engineered human
cardiovascular prostheses such as heart valves is an individual process. So far
no “gold standards” for the cell source, the scaffold material and the in vitro
culture conditions are available. In a recent project we have focused on the
evaluation and establishment of first standards for the in vitro fabrication of
tissue engineered human cardiovascular structures. The aim is to integrate these
standards into a catalog of parameters to guarantee controlled and reproducible
management and quality of the fabrication process under Good Manufacturing
Practice (GMP) conditions.
Methods and Results: In our laboratory we have established the isolation
and cultivation of human vascular cells from different sources, e.g. the human
umbilical cord. Recently, we have replaced the supplements in the present
protocols by nutrients conforming to GMP with the aim to establish an individual
cell bank and then to fabricate tissue engineered heart valves using these
cryopreserved cells. Further, we have analyzed different polymeric scaffolds as
carriers and modified the fabrication process accordingly. We have developed a
new bioreactor system combining optimal cell distribution and adjacent in vitro
conditioning in the same device for tissue engineered heart valve constructs.
An adjacent measuring unit is able to collect and monitor different parameters
during the fabrication process to provide detailed data on the tissue developing
inside the bioreactor system. The parameters are displayed via online monitoring
in a specific LabView application throughout the in vitro conditioning process.
Initial trials have demonstrated the feasibility of monitoring and controlling the
development of tissue-like structures.
Conclusions: Online monitoring of the different parameters gives information
on the developing tissue and is used to control and manage the fabrication
process. Adjustment to nutrients complying with GMP is one step towards
obtaining permission for fabrication for future clinical applications.
P156 (182)
DEVELOPMENT OF ULTRASONIC-RANGE VIBRATORY MICROINJECTION
SYSTEM
F. Miyawaki1, J. Hasegawa2, Z. Rejep1, D. Kudereti1, R. Okada1, K. Kobayashi2
1
Tokyo Denki University, Saitama, Japan; 2Takusyoku University, Tokyo, Japan
Objectives: To raise the efficiency of gene transfer, we have been developing
the vibratory microinjection (VM) system, which pierces a cell and injects
foreign gene into nucleus while a micropipette is longitudinally vibrated. We
previously reported the auditory-range VM in this conference, and will present
the ultrasonic-range VM (UVM).
Methods: The frequency of UVM in this study was 40 kHz; the amplitude
was controlled by voltage applied to the vibrator. A total of 605 fertilized eggs
obtained from 40 BDF1 mice were randomly allotted to UVM group and an
ordinary non-vibratory microinjection (OM) group. In each group, 30 eggs were
pierced with a single micropipette. GFP gene was injected. Each injection
procedure was videotaped and those microscopic images were subsequently
analyzed to measure how deeply each egg was depressed at the insertion point
and to determine how quickly each injection was finished. After injection, the
eggs were cultured for 4 days and their embryonic development was examined
periodically.
Results: 1) UVM group showed significantly smaller depression rates than
OM one did: 25.8 ± 6.1% (N = 233) vs. 32.0 ± 6.1% (N = 230) (p < 0.0001,
Student’s t test). 2) UVM significantly shortened the injection time, duration from
the moment a micropipette touched the zona pellucida until the moment it was
drawn out of the egg: 2.50 ± 1.39 sec (N = 233) vs. 4.02 ± 1.65 sec (N = 230) (p <
0.0001, Student’s t test). UVM thus reduced the time by 38%. 3) On 4th day after
injection, 129 eggs out of 303 (42.6%) in UVM group developed to blastocyst,
the final stage in culture, whereas 111 of 302 (36.8%) did in OM group (p =
0.14). The death rates were 24.5% (75/303) and 29.1% (88/302) in UVM and OM
groups, respectively (p = 0.22).
Conclusions: Ultrasonic-range VM facilitated cellular piercing and improved
efficiency of gene transfer because of its much shorter injection time. It also
showed better embryonic development, thus suggesting that UVM can
contribute to production of more transgenic mice than ordinary microinjection.
482 © 2010 Wichtig Editore - ISSN 0391-3988
P157 (188)
Functioning of cells encapsulated in nano-thin membrane
for biomedical purposes
M. Borkowska, J. Kinasiewicz, M. Antosiak-Iwanska, E. Godlewska,
L.H. Granicka
Institute of Biocybernetis and Biomedical Engineering, Polish Academy of
Science, Warsaw, Poland
Objectives: The implantation of bioartificial systems consisted of biological
material encapsulated in the membranes, producing biologically active
substances may be an alternative for implants achieved from donors. Our aim
was the evaluation of chosen polyelectrolyte (PE) layers configuration suitability
for encapsulation of cells.
Methods: The nano-thin PE bilayer consisted of polylysine and
poly(ethyleneimine) with incorporated fullerenol was deposited on Jurkat cells
(human lymphocyte T cell line) using electrostatic interactions in layer-by-layer
process. The purpose of such coating application was minimizing the system
volume as well as diminishing oxidative stress. The cells were coated with two
PE bilayers. Different fullerenol concentrations were applied. Cells functioning
was evaluated during 8-day culture by mitochondrial activity assessment in MTT
test in spectrophotometer. As a control nonencapsulated cells were cultured.
Results: After 8-day culture there was no difference in mitochondrial activity
of cells coated with shells containing different fullerenol concentrations (mean
absorbance for different nanoshell concentrations was 0.082±0.007), the
mitochondrial activity was comparable for nanocoated cells as compared to a
control for different fullerenol concentrations.
Conclusions: The applied coatings may have application for encapsulation of
cells for biomedical purposes.
P158 (192)
Functioning of microorganisms encapsulated in membrane
system for anti-tumor purposes
L. H. Granicka1, R. Stachowiak2, J. Wiśniewski2, M. Łyżniak3, J. Bielecki2,
J. Kawiak1,3
1
Institute of Biocybernetics and Biomedical Engineering, Polish Academy of
Science, Poland; 2University of Warsaw, Faculty of Biology, Department of
Applied Microbiology, Poland; 3Medical Center of Postgraduate Education,
Warsaw, Poland
Objectives: Encapsulation of bacteria in a semipermeable polymer membrane
opens several technological possibilities. Some encapsulated microorganisms
may carry a transfected gene, and thus become a source of regulatory factors.
Our aim was to evaluate the impact of factors produced by modified organisms
Prokaryotae encapsulated in elaborated membrane system on functioning of
eukaryotic cells for further applications in anti-tumor therapy.
Methods: The activity of genetically modified bacteria Bacillus subtilis (Bs)
encapsulated in elaborated for this purpose membranes was evaluated by
assessment of their impact on human leukaemia cells, obtained from patients.
In primary experiments with nonencapsulated biological material it was
observed that proteins secreted by recombinant Bs strain including listeriolysin
(LLO), in proper environment have cytolytic features and may induce apoptosis
and necrosis in cells. 1) Encapsulated in membranes IPTG induced bacteria
were cultured in sheep erythrocytes suspension for 48 hr. The impact of
bacterial products was evaluated spectrophotometrically. 2) Encapsulated in
membranes IPTG induced bacteria were cultured in suspension of peripheral
blood mononuclear cells obtained from leukaemic patients for 24 hr. The impact
of bacterial products was evaluated in flow cytometer. As a negative control the
cells were cultured in presence of empty membranes.
Results: Encapsulated Bs demonstrated hemolytic as well as cytolytic activity.
The number of erythrocytes in suspension cultured in encapsulated bacteria
presence declined twice. It was observed that the viability of leukaemic cells
declines as compared to a negative control (24.6±6.4[%] and 9.5±1.0[%] dead
cells, respectively). This indicates effective action of bacterial toxins produced
by membrane coated Bs cells.
Int J Artif Organs 2010 ; 33 ( 7): 483

Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia

Artificial Kidney 2 P161 (309)

PREDICTORS OF NATIVE FISTULA THROMBOSIS IN HEMODIALYSIS
PATIENTS
A. Asani, P. Dejanov, V. Gerasimovska, A. Oncevski, L. Trajceska, V. Amitov,
P159 (266)
V. Pusevski, G. Severova-Andreevska, A. Sikole
EFFECT OF PLASMAPHERESIS ON CLINICAL IMPROVEMENT IN
University Clinic of Nephrology, Skopje, R. Macedonia
SYSTEMIC DISEASES ASSOCIATED WITH RENAL FAILURE
L. Tozija, Z. Petronijevic, I. Nikolov, A. Asani, K. Cakalaroski
Objectives: Acute thrombotic complications of native fistulas remain a
University Clinic of Nephrology, Medical Faculty, University "Sts Cyril and
proportionally increasing complication in hemodialysis patients. We aimed to
Methodius", Skopje, R. Macedonia
investigate the associated factors with thrombosis of fistulas.
Methods: 121 hemodialysis patients of mean age: 56.4±13.0 years were
Objectives: Prognosis of a systemic disease for patients with fulminant vasculitis
included in a cross-sectional study. Excluding criteria: malignant disease,
admitted to the intensive care unit (ICU) is very poor. Renal involvement is
thrombocytosis and inadequate antithrombotic prophylaxis. After adjusting for
typically present in these diseases and often referred to as a rapidly progressive
initial failures (ie, failures within the first 2 months of fistula use), the rates of
glomerulonephritis with high morbidity and mortality. Early and accurate
thrombosis of native AV fistulas, as number of episodes per patient year, were
diagnosis and aggressive treatment are essential to optimizing outcomes while
calculated for each patient. Stenosis and corrections of fistulas were closely
avoiding unnecessary immunosuppressive therapy. Plasmapheresis or plasma
observed. Clinical and dialysis history were notified including referral of patients
exchange (PE) may influence the activity of vasculitis not only by removal of
to nephrologists and presence of preventive fistula (pAVF). Multivariate linear
pathogenic autoantibodies, but also by lowering of serum levels of circulating
regression analysis was performed.
cytokines.
Results: In the Univariate model presence of diabetes mellitus (r=0.155,
Methods: We present here three patients treated in ICU at the University
p=0.045 ), age above 65 years (r=0.171, p=0.031), lower dialysis vintage (r=-218,
Clinic of Nephrology in Skopje, with confirmed diagnosis of systemic disease
p=0.017), higher C-Reactive Protein (0.206, p=0.012), Hyperlipoproteinemia
associated with respiratory symptoms and a renal affection manifested as
(HLP) (r =0.277, p=0.002), Intra - Dialytic Hypotension (r=0.183, p=0.044) and
glomerulonephritis. In two patients we confirmed diagnosis of Morbus Wegener
better nutritional support (r=-0.160, p=0.04) correlated with higher rates of fistula
and in one patient we confirmed Goodpasture syndrome. Initial hospital admission
thrombosis. The presence of pAVF lowered significantly the risk for thrombosis
was marked by serious respiratory symptoms with development of important
(r=0.248, p=0.008). The early referral to nephrologists, higher education level and
deterioration of renal function as well as anemia and hypoproteinemia. Dialysis
early detection and treatment of stenosis lowered the risk, but insignificantly.
treatment was introduced. After diagnosis confirmation, immunosuppressive
Multiple analyses revealed that HLP, and CRP were the strongest predictors of
treatment with prednisolone and cyclophosphamide were introduced as well
thrombotic events and presence of preventive AVF predicted lowering the risk.
as plasmapheresis. This resulted in a disappearance of signs and symptoms of
Conclusions: Quality improvement strategies to improve the prevalence of
systemic inflammation and in an important improvement of respiratory symptoms
fistulas should focus on wide population education, early referral to nephrologists
and moderate improvement of kidney function. Patients were discontinued from
and predialysis creation of fistulas. Early recognizing of hemodynamically
dialysis and a regular control of renal function by nephrologist was suggested.
significant stenosis is crucial. Further studies are needed to investigate whether
Conclusions: In patients with clinically and histologicaly confirmed systemic
the treatment on HLP will lower the rate of thrombosis of fistulas.
vasculitis associated with renal disease, plasmapheresis therapy addition must
be considered as an effective modality of treatment.
P162 (223)
EPO DOSES IN HEMODIALYSIS PATIENTS WITH HEPATITIS C
P160 (247)
P. Dzekova Vidimliski, G. Severova-Andreevska, L. Trajceska, V. Pusevski,
Hantavirus pulmonary syndrome with acute renal failure
G. Selim, S. Gelev, V. Amitov, A. Sikole
A. Asani, L. Tozija, Z. Petronijevic, I. Nikolov, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Department of Nephrology, Faculty of Medicine, Skopje, R. Macedonia
Objectives: Attenuated anaemia was detected in hemodialysis patients with
We report a case of a 40-year-old patient with acute renal involvement in
hepatitis C virus (HCV) infection. The aim of the study was to compare the Epo
Hantavirus pulmonary syndrome (HPS) observed at the Department of
doses needed for maintaining stable hemoglobin levels between HCV positive
Nephrology, Faculty of Medicine, Skopje, Republic of Macedonia. This
and HCV negative hemodialysis patients.
syndrome was first recognized in 1993. Although rare, HPS is a potentially
Methods: A retrospective study was conducted on 110 hemodialysis patients.
deadly syndrome and progresses rapidly to potentially life-threatening breathing
Monthly laboratory samples were collected between January 2009 and January
problems. The Hantan and Seoul viruses are responsible for hemorrhagic fevers
2010. The HCV status was determined by anti-HCV antibodies, tested by ELISA-
with renal syndrome (HFRS) of severe to moderate expression in Asia and also
third generation assay. Criteria for patients exclusion from the study were: active
in the Balkans.
gastrointestinal bleeding, chronic infections, active treatment with interferon,
The patient was working in a wood factory and he was in contact with wood,
polycystic kidney disease, and acquired cystic kidney disease.
dust and mice, and presented with fever, weakness, headache, abdominal pain
Results: Of 110 patients, 60 (54.5%) were HCV positive and 50 (45.5%)
and generalized myalgia, cought, lumbar pain and hematuria (clinical features
were HCV negative. Mean hemoglobin level in the HCV positive patients was
of the patient who was with serum creatinine level of 535 micromole/L). Other
12.26±1.22 g/dL compared to 11.46±3.13 g/dL for the HCV negative patients,
following laboratory findings were leukocytosis, with neutrophylia, and reduction
(p=0.069). HCV positive patients received significantly lower Epo doses for
of serum sodium and calcium, and a decrease in serum complement C4 (0.06
maintaining stable hemoglobin levels compared to HCV negative patients
g/L).
(57.30±52.92 vs. 78.75±37.09 U/kg/w, p<0.018). Anti-HCV positivity was also
His clinical course progressed through febrile, hypotensive, oliguria and polyuria
significantly associated with dialysis duration (p<0.000), serum levels of alanine
phases. The diagnosis of Hantan virus infection was proven at the first hospital
aminotransferase (p<0.000) and aspartate aminotransferase (p<0.007). Serum
week by an indirect immunofluorescent IgG reaction with a titer of 1:2048 after
level of hemoglobin (OR=0.44, 95%CI, 0.31-0.62, p=0.000), serum level of
a four-day hospitalization in our clinic. The patient was successfully treated
iron (OR=0.06, 95%CI, 0.01-0.45, p=0.006), and number of transfused blood
with supportive management, but he developed a severe clinical course
products (OR=7.86, 95%CI, 1.55-40.22, p=0.016) were identified as independent
with acute renal failure requiring dialysis. Because of manifesting respiratory
predictors of Epo doses in hemodialysis patients, with linear regression model.
insufficiency, hypo-saturation and need of assisted ventilation for 12 hours
Conclusions: Hemodialysis patients with HCV infection required lower Epo
we applied mechanically-generated positive pressure in Intensive Care Unit
doses to maintain the stable hemoglobin levels compared to HCV negative
of Anesthesiology and Reanimation Clinic. After 3 weeks his renal function
patients. Further studies should be conducted in order to identify the real
improved and serum creatinine levels were almost normalized.
reasons for lower Epo requirement in hemodialysis patients with hepatitis C.
Clinicians should be alert to the possibility of Hantavirus pulmonary syndrome
when examining patients with symptoms of fever, renal function impairment and
hemorrhagic tendency.

© 2010 Wichtig Editore - ISSN 0391-3988 483

Int J Artif Organs 2010 ; 33 ( 7): 484
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P163 (222)
LIVER DISEASE PROGRESSION AND AMINOTRANSFERASE ACTIVITY IN
HEMODIALYSIS PATIENTS WITH CHRONIC HEPATITIS C
P. Dzekova Vidimliski, L. Trajceska, G. Severova Andreevska, V. Pusevski,
G. Selim, S. Gelev, V. Amitov, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: The aim of the study was to determine the predictors of
aminotransferase activity in hemodialysis patients with chronic hepatitis C.
Methods: Eighty hemodialysis patients with chronic hepatitis C were enrolled
in the study and followed for 48 months. Serum levels of aminotransferases
were measured monthly with standard automated analyzers. The presence of
HCV antibodies was tested by ELISA assay and HCV RNA was determined by
reverse transcriptase polymerase chain reaction. Ultrasound examination with
measurement of morphological parameters (liver size, morphology, surface,
echogenicity, and spleen volume) and hemodynamic parameters (portal vein
diameter and portal vein mean flow velocity) was done in all patients.
Results: According to the serum levels of alanine aminotransferase (ALT),
during the follow-up, patients were divided into two groups. The first group
consisted of 34 patients with persistently normal levels of ALT. The second group
included 46 patients with elevated levels of ALT. Genotype 1 was the dominant
genotype in both groups (78 patients, 97.5%). Patients with elevated ALT
levels were characterized with significantly shorter dialysis duration (p=0.048)
and significantly shorter duration of HCV infection (p=0.005) compared to
the patients with persistently normal levels of ALT. The values of measured
ultrasound parameters were not significantly different between the two groups.
The univariate analysis identified higher serum level of direct bilirubin (p=0.044),
shorter duration of dialysis (p=0.048), and shorter duration of HCV infection
(p=0.005) as potentional predictors of elevated serum ALT levels in dialysis
patients. After stepwise logistic regression, none of the potential predictors was
independently associated with elevated ALT levels.
Conclusions: Serum aminotransferase levels are poor predictors of liver disease
progression in hemodialysis patients with chronic hepatitis C.
P164 (244)
Hypertension as modifiable risk factor for coronary heart
disease in hemodialyzed patients
H. Korca, M. Gashi, D. Kocinaj
UCC of Kosova, Prishtine, Kosova
Objectives: Many studies evaluated coronary heart disease (CHD) risk factors in
hemodialyzed patients (HD). Patients with end-stage renal disease (ESRD) have
accelerated rate of CHD including increased mortality after an acute coronary
syndrome and myocardial infarction. Hypertension is a major risk factor.
Methods: We examined the relationship between known risk factor-hypertension
for CHD and incidence of CHD in men (44%) and women (56%) aged from 20 to
78 years (men age 56.4±13.9), hemodialyzed at our center.
Results: During two years of follow-up in 125 patients on hemodialysis mean
systolic blood pressure (BP) was 138.8±25.4 and mean diastolic BP was
77.6±14.4, with the mean heart rate 78.2±14.9. Blood pressure higher than
140 mmHg was associated with increased risk of CHD. Higher systolic BP
of 10 mmHg was associated with RR of 1.2 (1.12-1.25) compared with lower
systolic BP independent of age, gender, body mass index (BMI), cholesterol,
triglycerides and diabetes.
Conclusions: Our results confirm the importance of hypertension as a modifiable
risk factor for CHD, an important predictor of mortality in patients with ESRD as
it accounts for almost 50 percent of deaths.
P165 (186)
LIPOPROTEIN PROFILE IN CHRONIC HEMODIALYSIS PATIENTS AND
HEMODIALYSIS ANTICOAGULATION
B. Vajdič, R. Ponikvar, V. Persic, S. Pejanov, A. Marn-Pernat, J. Kovac,
M. Benedik, J. Varl, B. Knap, J. Gubensek, B. Kersnic, J. Buturović-Ponikvar
Department of Nephrology, University Medical Center, Ljubljana, Slovenia
Objectives: The aim of our single-center retrospective cross-sectional study
was to analyze lipoprotein profile in chronic dialysis patients and to compare it
among groups with different types of hemodialysis anticoagulation.
Methods: The study cohort included 207 patients with end-stage kidney
disease who were on hemodialysis treatment in our dialysis center in July 2009.
Baseline values of lipoprotein profile from regular month laboratory tests were
analyzed and the type of hemodialysis anticoagulation – unfractioned heparin
(UFH), low molecular weight heparin (LMWH) or regional citrate anticoagulation
(RCA) – was recorded. The use of statins was recorded as well. Due to the small
484 © 2010 Wichtig Editore - ISSN 0391-3988
number of patients (7) receiving RCA they were excluded from the lipoprotein
profile analysis.
Results: Of 207 patients (mean age 64 years +/- 15.2 years, range 23 to 95
years) 117 (56.5%) were males. 55.1% of patients were receiving LMWH for
hemodialysis anticoagulation, 41.5% were receiving UFH and 3.4% were
having RCA. 21 patients were taking statins at the time of analysis: 9 (7.8%)
patients from the group receiving LMWH, 11 (12%) patients from the group
receiving UFH and 1 (14%) from the group receiving RCA. Baseline values of
total cholesterol, LDL and triglycerides were lower in the group receiving LMWH
compared to the group receiving UFH, but there was no significant difference
between the LMWH and UFH treatment.
Conclusions: Only a minority (less than 10%) of chronic hemodialysis
patients had high total and LDL serum cholesterol level and are using statins.
Anticoagulation with LMWH was associated with slightly lower serum cholesterol
and triglyceride levels, however, the difference was not significant.
P166 (85)
DOES THE HIGHER NUMBER OF DWELLS WITH APD RESULT IN BETTER
SOLUTE REMOVAL COMPARED TO CAPD?
S. Eloot, W. Van Biesen, R. Vanholder
Renal Divison, Gent University Hospital, Ghent, Belgium
Objectives: Two observational studies showed more solute removal (SR)
of protein bound solutes with hemodialysis, while time averaged plasma
concentrations (TACs) were not strikingly higher or even markedly lower in
peritoneal dialysis (PD) patients. Furthermore, analogous discrepancies were
found among PD modalities, with equal SR but higher TAC in automated PD
(APD) versus continuous ambulatory PD (CAPD). On the other hand, one could
expect better SR in APD compared to CAPD due to the higher number of
exchanges, especially in cases of high transporter PD membranes and/or small
solutes. To clarify those discrepancies, a cross-over study of APD and CAPD
treatment was performed investigating SR and TAC.
Methods: Nine chronic kidney disease patients on either CAPD or APD were
included in a cross-over study performing at random 24h of CAPD and APD
at midweek. During the 24h test session, 4 and 6 exchanges were performed,
respectively, in CAPD and APD, while PD fluid and urine were collected and
kept cooled. A blood sample was taken before each 24h test session (TAC).
Blood samples were immediately centrifuged and plasma was stored at
-80°C until analysis. All samples were determined for urea, creatinine (CREA),
phosphor, IL1B, beta-2-microglobulin, total protein, uric acid (UA), hippuric
acid, 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid, indoxyl sulfate,
indole acetic acid, and p-cresyl sulfate. Solute removal (SR) and total clearance
(K) were calculated for each PD modus.
Results: PD dwell volume was significantly different (p=0.004) as defined by the
therapy, while urine output was borderline higher for CAPD (p=0.059). For all
solutes, no differences were found for the TAC, while SR and K were significantly
higher in CAPD for CREA (p=0.005 and 0.013) and UA (p=0.047 and 0.033).
Conclusions: Although the number of dwells is higher in case of APD, CAPD
showed improved solute removal and total clearance for small solutes like
creatinine and uric acid.
P167 (159)
HOMOCYSTEINE LEVELS AND ERYTHROCYTE GLUTATHIONE
S-TRANSFERASE ACTIVITY IN A HEMODIALYSIS POPULATION
A. Noce2, C. Tozzo2, M. Dessi1, O. Durante2, S. Manca-di-Villahermosa2,
R. Massoud1, G. Ricci3, N. Di Daniele2
1
Department of Laboratory Medicine, Tor Vergata University Hospital, Rome,
Italy; 2Nephrology and Dialysis Unit, Tor Vergata University Hospital, Rome, Italy;
3
Department of Chemical Sciences and Technologies Tor Vergata University,
Rome, Italy
Objectives: Aim of the study was to evaluate the relationship between total
plasma homocysteine (Hcy) and erythrocyte glutathione S-transferase (e-GST)
activity in 62 ESRD patients on maintenance hemodialysis (MHD) and in 57
healthy controls.
Methods: Plasma total Hcy was assayed by an HPLC method using reversed-
phase separation and fluorescence detection. Erythrocyte e-GST activity was
detected by a photometric method applied on an automatic system of clinical
chemistry at 340 nm with the standard substrate (1-chloro-2,4-dinitrobenzene,
CDNB) and co-substrate (reduced glutathione).
Results: Over-activity of glutathione S-transferase (GST) was detected in the
erythrocytes of uremic patients. Either mean e-GST activity and mean plasma
Hcy levels were increased in HD patients compared to controls (10.47±2.86
U/gr Hb versus 5.63±1.7 U/gr Hb, p < 0.0001; 52.42±28.63 μmoli/L versus
Int J Artif Organs 2010 ; 33 ( 7): 485
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
13.65±6.13 μmoli/L, p < 0.0001). Further, a significant direct correlation was
found between plasma Hcy levels and e-GST activity (r=0.79, p<0.0001) in HD
patients, whereas no correlation was observed between plasma Hcy and E-GST
activity in the control group. Since it was observed that glutathione peroxidase
(GPx) activity is inhibited by high plasma concentrations of Hcy (Durmaz A,
J Enz Inhib Med Chem 2007), the increased E-GST activity maybe due to an
enhanced oxydative stress always observed in HD patients and in particular
under severe hyperhomocysteinemia conditions.
P168 (291)
DOES RENAL ARTERY RESISTIVE INDEX correlate with
GLOMERULAR FILTRATION RATE?
P. Avramovski1, P. Janakievska1, M. Koneska2, R. Pejkovski1, A. Sikole3
1
Clinical Hospital, Bitola, Macedonia; 2Medical Center, Prilep, Macedonia; 3Clinic
of Nephrology, Faculty of Medicine, Skopje, R. Macedonia
Objectives: Resistive index (RI) is a simple parameter that can be derived from
an ultrasound Doppler spectrum which describes the percentage reduction
of end-diastolic blood flow (Vmin) in a vessel in relation to maximal systolic
blood flow (Vmax): RI=(Vmax-Vmin)/Vmin. Glomerulal filtration rate (GFR) was
calculated by Cockcroft – Gault formula. The aim of this study was to evaluate
the relation of GFR to renal RI in patients with different stages of renal failure.
Materials and Methods: Sixty-seven hypertensive patients (28 females, 39
males, mean age 54±9.87) with GFR less than 60 ml/min/1.73m2 (RR~150/95)
mmHg were included in the study. Twenty healthy, normotensive volunteers (13
females, 7 males, mean age 45±6.9) served as controls. We estimate blood
pressure, creatinine level and the blood speed in segmental arteries by Doppler
ultrasound machine Toshiba SSA-340A. The RI was calculated from the blood
velocities and GFR from the level of creatinine and demographic data for
patients (age, body mass, gender).
Results: Renal RI was significantly higher in the patient group [(RI=0.749
(0.654–0.796) p<0,001], compared to the control group [RI=0.658 (0.632–
0.698), p=0.003)]. RI correlated significantly with effective renal plasma flow
(GFR=43±17.8 ml/min/1.73m2) (r=-0.5; p=0.003) in the patient as well as in the
control group (GFR=96±12.8 ml/min/1.73m2). The RI indices did not correlate
with serum creatinine in the control group, the patient group, or the mean arterial
blood pressure.
Conclusions: Renal RI seems to be closely related to the parameters of renal
hemodynamics and GFR in patients with chronic renal failure.
Hemodialysis 3
P169 (306)
INFECTION WITH ANTIMICROBIAL-RESISTANT MICROORGANISMS IN
PATIENTS WITH TUNNELED CUFFED HEMODIALYSIS CATHETERS
V. Gerasimovska , A. Oncevski, B. Gerasimovska-Kitanovska, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Catheter-related bloodsteram infection (CRBI) is a frequent complication among
hemodialysis (HD) patients (pts) using tunneled cuffed hemodialysis catheters
(TCC). The purpose of this study was to evaluate the association between
positive blood culture and antimicrobial management of pts with CRBI. During
the 3 year study period we analyzed a group of 123 pts receving chronic HD via
181 TCC. Duration time of TCC were 9500-10500 days, average 139-429 days.
TCC were divided in 3 groups: Gr 1 - tunneled femoral catheters TFC-103 (77
pts); Gr 2 - tunneled jugular catheters TJC-41 (24 pts); Gr 3 - tunneled subclavian
catheters TSC-37 (22 pts). All pts with TCC were monitored for infection and
data recorded for each patient included: clinical signs of infection conected with
HD, episodes of CRBI, blood culture from catheter and peripheral vein when
we had a suspicion of infection, antibiotic therapy and clinical outcomes. In Gr
1TFC- 21 cathet had 41 episodes of CRBI successfully treated with antibiotics
(systemically and antibiotic “lock” therapy) and unsuccessful in 6 cases (5.8%).
Microbiologically we isolated S. aureus, Staphyl coagulasa negative and
Enterococcus + Pseudomonas together. Infective rate was 4.1 infective
episodes/1000 cath days. Gr 2 TJC-7 catheters had 30 episodes of CRBI
successfully treated with antibiotics, and unsuccessful in 4 cases (9.7%). We
isolated again S. aureus, and Acinetobacter + Enterococcuss. Infective rate
was 2.8 infective episodes/1000 catheter days. Gr 3TSC- 14 catheters had 32
episodes of CRBI successfully treated and unsuccessful in only 1 case (2.7%).
We isolated again S. aureus. Infective rate was 3.6 infective episodes/1000
cath days. The initial AB regimens were Vancomy/Cefotaxim or Ciprofloxacin.
Antibiotic therapy was statistically significant for catheters survival especially in
© 2010 Wichtig Editore - ISSN 0391-3988
TSC (log rank test=0.06) and using multivariant analysis, only in this group we
found that positive blood culture (p=0.0008295) has prognostic value as a risk
factor for free survival time. We concluded that the use of AB therapy was a
successfully treatment in eradicating CRBI.
P170 (92)
THE EFFECT OF HIGH-FLUX HEMODIALYSIS ON QUALITY OF LIFE IN
DIALYSIS PATIENTS
V. Pusevski, D. Mladenovska, L. Trajcevska, S. Gelev, V. Amitov, A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: The nutritional support, dialysis treatment tolerability and adequacy
have a major impact on the Quality of life (Qol) in dialysis pts. We evaluated the
effect of high-flux hemodialysis on Qol, intra- and interdialytic symptoms.
Methods: The pts were stable, well compliant hemodialysis pts with Chronic
interdialytic hypotension. Pts with dialysis vintage less than 3 months, non
managed anemia, sleep disturbance and severe intradialytic hypotension or
severe cardiovascular comorbidites were excluded. The study was patient-blind
single cross-over with treatment period of 6 months. Both conventional and
high-flux membranes were polysulfone, the dialysate was bicarbonate, dialysate
sodium was held constant, temperature fluctuated from 36 to 37˚C. Presence
of intradialytic episodes of hypotension and requirements of concentrated
sodium were closely observed. Interdialytic symptoms as appetite score (1-
5) and interdialytic weight gain as percentage of dry body weight (IDWG/b.w.)
were notified. Qol was assessed by SF-36 questionnaires at the end of each
treatment period. Seven pts completed both phases.
Results: The spKT/V value was lower during conventional than high-
flux treatment (p less than 0.028). Intradialytic hypotensive episodes and
requirements of concentrated sodium per dialysis were less severe during high-
flux than conventional treatment (p=0.107), (p=0.063), respectively. Appetite
showed borderline significant improvement by the high-flux dialysis (p=0.059)
and IDWG/b.w. was insignificantly increased (p=0.446). The phosphorous and
C-reactive protein decreased with high-flux dialysis but, insignificantly (p=
0.237), (p=0.527). The Normalized Protein Appearance (nPNA) and dry weight
of the pts significantly improved (p=0.039), (p=0.038).
Conclusions: High-flux dialysis improved the tolerance of the dialysis treatment,
adequacy and beneficially affected the appetite and nutritional support of the
dialysis pts. The influence of high-flux dialysis on Qol in dialysis pts is to be
established in larger study population.
P171 (295)
Cardiac surgery in patients under chronic hemodialysis
T. Anguseva, Z. Mitrev, D. Nikolovska, V. Kostova, I. Kirova
Special Hospital for Surgery Fillip II, Skopje, R. Macedonia
Objectives: Open-heart surgery carries a high risk for hemodialysis patients.
This study focuses on the short and long-term outcomes of hemodialysis
patients undergoing heart surgery.
Material and Methods: A total of 10 chronic renal failure patients on hemodialysis
therapy underwent some kind of cardiovascular surgery between May 2008 and
April 2010. One had a valve abnormality, and the remaining nine had coronary
artery disease. All of them were hemodialyzed the day before surgery and 24–48
h after the operation, with Prismaflex CVVHD.
Results: Six recovered well after surgery, four died of septic shock: one was in
terminal congestive heart failure. All operative deaths occurred in the patients
who underwent non-elective surgery or were preoperatively in New Heart
Association (NYHA) class IV. The factors having an impact on morbidity and
mortality seem to be more related to the previous clinical situation and to the
urgency of the operation than to the status of chronic renal failure.
Conclusions: An early and adequate assessment of the candidates, when
possible avoiding emergency surgery and acute left ventricular dysfunction,
as well as careful management during cardiopulmonary bypass procedures
(CPB) and the immediate post-surgical period will certainly improve the result
of cardiac surgery in these patients, making it similar to those who are not in
chronic renal failure.
P172 (133)
AUTOMATIC EVALUATION OF VASCULAR ACCESS IN HEMODIALYSIS
PATIENTS
C. Rose1,4, B. Béné2, J. Chanliau3, F. Charpillet4
1
Diatelic, Nancy, France; 2Gambro, Meyzieu, France; 3ALTIR, Nancy, France;
4
INRIA, Nancy, France
The vascular access that allows to perform the extra-corporeal circulation, is
485
Int J Artif Organs 2010 ; 33 ( 7): 486
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
usually a vein of the arm that has been enlarged by a surgical creation of a
fistula. The prevention of complications such as stenosis or thrombosis of the
vascular access is a key issue in hemodialysis treatment.
Many dialysis machines measure ionic dialysance by conductivity measures on
the dialysate fluid. Ionic dialysance is an indicator of small molecule transfers
through the dialysis membrane. Previous works have shown that the follow-up
of the dialysance and the pressures along the extra corporeal circuit can help to
detect at an early stage a potential complication on the vascular access.
The difficulty of automating the follow-up is the large variability of the measures
and the need to detect tendencies. Dynamic Bayesian Networks (DBN) allow to
formalize expert knowledge as a graphical stochastic model adapted to reasoning
under uncertainty. In a DBN the state of the patient and the measurements
are represented by interconnected temporal random variables. The relations
between those variables are described using probability distributions. The
proposed approach is based on a supervised learning of a DBN for classifying
the dialysis sessions according to a risk score describing the medical situation
(0: no risk,1: mild risk, 2: severe risk). The training of the system was performed
using a dataset labelled by a medical expert.
The evaluation of the results was done performing a double-blind analysis of
real data. The result was an 85% agreement rate between the human expert
and the automated analysis.
Human score 0; Human score 1; Human score 2
Auto score 0; 763; 55; 1
Auto score 1; 80; 196; 15
Auto score 2; 8; 20; 66
The purpose of the system is to assist the human expert by reporting
abnormalities. The results show that a score 2 reported by the human is rarely
missed by the automated analysis (only 1 case) whereas the opposite is more
frequent (8 cases). The final decision to further investigate a case is taken by
the human expert.
P173 (292)
Correlation between inflammation and cardiovascular
disease on hemodialysis unit in prishtina
H. Korca, M. Gashi, D. Kocinaj
UCC of Kosova, Prishtina, Kosova
Objectives: In chronic kidney disease (CKD), a common cause of death is
cardiovascular disease (CVD). Traditional risk factors can not explain the
increasing incidence and prevalence of CVD in this group of patients, we would
like to suggest that we can explain this with the presence of inflammation which
has a major role on vascular atherosclerosis and together with nontraditional
risk factors which they accelerate each other.
Methods: In this cross-sectional study, we enrolled 123 chronic HD patients.
Hematological, biochemical parameters were determined. Cardiovascular
disease (CVD) was investigated by ultrasonic and electrocardiography signs
of LVH. The presence of inflammatory reaction was assessed by C-reactive
protein (CRP) and negative reactant of acute phase response serum albumin
(S-albumin).
Results: We found that total of 123 chronic HD patients, predominantly male 69
(56.1%), middle aged are 56.4±13.9, mean age 60 (52%) with diabetes mellitus
are 24.4%. Inflammation marker CRP was positive 37.1%, mean 11.2±8.0
mg/L, no correlation between gender, no significance of age. Negative reactant
of acute phase responses S-albumin decreased to 57.7%, female 63.8%,
mean 33.8± 4.2 g/L. Left ventricular hypertrophy to 53.7%. Weak correlation is
observed between systolic function and reactant of acute phase inflammation.
Conclusions: These results indicate the presence of inflammation and weak
correlation with systolic function. The presence of old age with low immunity
together with inflammation cause in this population (HD patients) an increase in
prevalence and incidence of CVD.
P174 (276)
Development of secOndary hyperparathyroidism at the
department of hemodialysis in Kocani
B. Panova, E. Grozdanova, M. Eftimov
General Hospital, Kocani, Department of Hemodialysis, Kocani, R. Macedonia
Objectives: Secondary hyperparathyroidism (sHPT) is one of the more serious
complications in dialysis patients and it is characterized with abnormalities in
mineral metabolism and bone disease. The aim of this study was to present the
development of sHPT at the HD patients in Kocani and distribution to without
clinical expression,with clinical expression and several clinical expressions.
Materials and Methods: Information was derived from the medical
documentation of patients. Retrospectiely we have analyzed 40HD patients (30
486 © 2010 Wichtig Editore - ISSN 0391-3988
male, 10 female). The following parameters were analyzed: clinical condition,
biochemical analysis (serum Ca, PO4, AF, PTH), X-rays, ultrasonography.
According to the results all patients were divided in three groups.
Results: First group includes 11 patients or 27.5%, male 7 (13.6%), female 1
(2.3%), without clinical manifestation of sHPT with iPTH<150pg/mL, AF<120U/L,
Ca>2.3 mmol/L, PO4<1.6 mmol/L, X-ray findings were normal, with average
HD period from 6 months to 3 years. Second group includes16 patients or
40%, 13 male (32%), 3 female (7.5%) with clinical manifestation of sHPT with
iPTH>150pg/mL, AF >12U/LCa<2.3 mmol/L, PO4>1.6 mmol/L, X-ray changes
(ROD) with HD period 3-10 years. Third group includes 13 patients or 32.5%,
10 male (25%), 3 female (7.5%) with expressed clinical manifestation with
iPTH>500 pg/mL, AF>300U/L, Ca 2 mmol/L, P>2mmol/L, X-ray with highlight
changes of ROD, average HD period >10years.
Conclusions: sHPT is one of the most frequent metabolic discorders in HD
patients and is correlated with the length of the dialysis period. Knowing the
consequences of sHPT, it is necessary to prevent, detect and set an adequate
treatment.
P175 (221)
Epidemiology of CKD-MBD in the Institute of Nephrology –
Struga
M. Zabzun
Institute of Nephrology, Struga, R. Macedonia
Objectives: Disorders of mineral and bone metabolism are one of the most
prevalent and serious abnormalities in dialysis patients. MBD are associated
with bone fractures, soft tissues and vascular calcifications. Patients with CKD-
MBD are with high risk of morbidity and mortality. Aim of this study was to
evaluate the distribution of the different types of CKD-MBD in the Institute of
Nephrology – Struga. Treatment strategies Study design: Type: Single center
study (epidemiological survey) Place: Institute of Nephrology Struga. Prospective
data analysis, Retrospective data analysis.
Materials and Methods: 156 Patients included, with clinical data analysis
= 70.9% of HD population in the Institute. Last 3 determinations of serum
biochemistry: s.Calcium (Ca); s.Phosphorus (P); total alkaline phosphatase
(TAP) Parathyroid hormone (i PTH) Bone mineral densitometry – BMC, single
photon absorptiometry – n=156, Bone biopsy, iliac crest bone biopsy with
double tetracycline labeling. n= 35 Bone hystomorphometric analysis n= 35,
Surgical parathyroidectomy (PTx) n= 8.
Results: We reached the in-target range for approximately 50% of our study
group, for the 3 main biochemical parameters. Calcium-carbonate is the most
used Phosphate-binder (96% of our study group) resulting in inadequate
Phosphor control and radiological evidence of soft-tissue calcifications.
Sevelamer group (4%) is with an adequate control of Ca – P axis, with minimal
complications, mainly gastrointestinal. iPTH is a useful diagnostic indicator in
predicting renal bone disease, but bone biopsy still remains the “gold standard“,
especially in patients with ABD. HPTBD is the most prevalent in our biopsied
study group (45.7%). ABD is found in 22% of our bone-biopsied study group.
Parathyroid intervention is crucial in the cases of nodular hyperplasia of the
glands. In our PTx study group there is a significant improvement of the event
for a long period.
P176 (76)
CLINICAL EXPeRIENCE WITH TRANSFUSION BLOOD RED CELL AND
EPOETIN BETA IN TREATMENT OF ANEMIC SYNDROME IN PATIENTS
On CHRONIC HEMODIALySIS at THE CENTRE FOR HEMODIALYSIS IN
GOSTIVAR-MACEDONIA
J. Neskovski, D. Jovceski, V. Jovceska, J. Zvezdakoska, R. Veliu, B. Aliu,
J. Jankoski, D. Apostoloski
Centre for Dialysis and Nephrology, Department of Transfusiology, General
Hospital Gostivar Private Health Organization, Nefromedika, Gostivar,
R. Macedonia
Investigations of effect on Transfusion blood red cell and Epoetin Beta
(intravenous application after hemodialysis), in treatment of anemic syndrome
on patients in hemodialysis. Investigations of effect on transfusion blood cell
application and Epoetin Beta, from dependents of high number on Hb, HTC,
Feritin, Serum Fe, MCV, blood pressure, application dose in different periods.
We take protocols for practical application on Epoetin beta (Studia Necker-
France, 50-60JE kg/tt in week), and transfusion blood red cell (under Hb 70gr/L-
massive hemorrhagic syndrome and perforation of set for hemodialysis for time
on treatment with dialysis). The numbers of patients on treatment with dialysis
at the Centre for hemodialysis in Gostivar are 50 patients (27 women and 23
men). Investigation time was 20 weeks. Epoetin beta was given three sessions
Int J Artif Organs 2010 ; 33 ( 7): 487
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
in week after hemodialysis and transfusion blood red cell application after acute
problems. After 20 weeks treatment with Epoetin Beta and transfusion blood
red cell, parameters (Hb, HTC, Serum Fe, Feritin) are significantly high, blood
pressure is good and good effect in lipids status. The number of transfusion
blood red cell is given with minimal percent (urgent transfusion applications
in acute problem – massive hemorrhagic syndrome and perforation on set for
hemodialysis for time on dialysis treatment). Every day, the quality of life is
significantly better and socialization of patients increases with good corrections
of anemic syndrome in dialysis patients.
P177 (310)
Mortality in the department of Hemodyalisis in Kocani for
the period 2005-2009
E. Grozdanova, V. Grozdanov, M. Eftimov
Department of Hemodylisis, Kocani, R. Macedonia
Objectives: According to WHO the most frequent reasons for increased
mortality are: cardiovascular diseases CVD, ischemic stroke (ICV), malignant
disease. Aim of this study was to present the mortality of this diseases at the
department of hemodyalisis in Kocani from 2005 to 2009.
Materials and Methods: Data were obtained from the medical documentation
of hemodyalsis patients, and were analysed for a period of 5 years.
Results: In 2005 of 41 patients, 7 patients died (17.1%), 4 male (9.7%), 3
females (7.4%). From CVD 3 males (7.4%), 2 females (4.8%), ICV 1 male (2.4%),
1 female (2.4%). In 2006 of 35 patients, 5 patients died (14%), 4 males (11%), 1
female (5.6%). From CVD 2 males (5.6%), 1 female (2.8%), ICV 1 male (2.8%),
other 1 male (2.8%). In 2007 of 35 patients, 4 patients died (11.4%). From CVD
1 male (2.7%), 2 females (5.7%), Other 1 male (2.7%). In 2008 of 37 patients,
3 patients died (8.1%), 1 male ( 2.7%), 2 females (5.4%). From CVD 1 male
(2.7%), 1 female (2.7%), ICV 1 female (2.7%). In 2009 of 44 patients. 3 patients
died (6.8%) 2 males (4.6%), 1 female (2.3%). From CVD 1 male (2.3%), 1 female
(2.3%), ICV 1 male (2.3%).
Conclusions: Cardiovascular dsease end ischemic stroke are often found in
hemodalysis patients and they are causes of high mortality among these.
Hemodialysis 4
P178 (210)
TROPONIN I LEVELS IN CHRONIC HEMODIALYSIS PATIENTS
V. Persic, J. Kovac, A. Marn-Pernat, R. Ponikvar, B. Knap, J. Varl, M. Benedik,
J. Gubensek, B. Kersnic, J. Buturovic-Ponikvar
Dialysis Center Zaloska, Department of Nephrology, University Medical Center,
Ljubljana, Slovenia
Objectives: A very high prevalence of Troponin-T (TnT) positive results has been
reported in asymptomatic patients with end-stage renal disease (ESRD) treated
with hemodialysis. On the other hand, elevated Troponin-I (TnI) in these patients
was reported less frequently. The aim of our single-center retrospective cross-
sectional study was to analyze serum levels of TnI in chronic dialysis patients in
association with presence of coronary artery disease (CAD) risk factors.
Methods: 220 patients on chronic hemodialysis in our center in December 2009
were included and Troponin I Ultra® levels from regular month laboratory values
were analyzed. A TnI concentration of >0.1 mcg/L (concentration that exceed
the 99th percentile value of the reference population) was considered abnormal.
Presence of CAD and traditional CAD risk factors were recorded – age, gender,
diabetes mellitus, arterial hypertension.
Results: The median age was 65±15 years (range 23-95), 59% (129/220) of the
patients were men, 33% (72/220) had diabetes mellitus, 82% (180/220) had
arterial hypertension, and 24% (52/220) had a history of coronary artery disease
(CAD). The median number of years on dialysis was 6.1±7.4 (range 1–36). None
of the patients had symptoms of coronary heart disease (CHD). Average TnI
value was 0.040±0.073 (range 0.006-0.827) mcg/L. 3.6% (8/220) patients, all
men, had abnormal levels of TnI. This subgroup of patients had at least two risk
factors for development of a CHD.
Conclusions: The vast majority of patients on hemodialysis does not have
elevated cardiac Troponin I values. Even minimal elevations of cardiac Troponin
I in such patients should not be attributed to their renal disease. Abnormal high
values of cardiac Troponin I in patients with ESRD should be assumed to be the
result of myocardial necrosis.
© 2010 Wichtig Editore - ISSN 0391-3988
P179 (102)
SEASONAL VARIATIONS IN BILIRUBIN IN DIALYSIS PATIENTS, A POSSIBLE
INTERPLAY BETWEEN NUTRITION AND SUNLIGHT
L. Trajceska¹, G. Severova¹, S. Arsov², A. Sikole¹
¹University Clinic of Nephrology, Skopje, R. Macedonia; ²University Medical
Center Groningen, Groningen, The Netherlands
Objectives: Seasonal variations of bilirubin in dialysis patients (pts) could
be partly explained by nutritients & vitamins deficiency in seasonal food
variations. Sunlight breaks down bilirubin, so it might play additional role on the
phenomenon. Aim: to explain the influence of sunlight and nutritional status (NS)
on bilirubin variations in dialysis patients.
Methods: 89 dialysis patients with stable hemoglobins were studied within a
year. Excluding criteria: liver disease, hemorrhage, transfusions, inadequate
dialysis, and vitamin supplements. NS was assessed by body mass index (BMI)
and subjective global assessment (SGA).
Results: The peak values for bilirubin in the group of well nourished pts (N=40)
occurred in January and in malnourished pts (N=17) in March. Lowest values
occurred in October for both groups. Except in January, bilirubin levels were
significantly higher in malnourished patients through the whole year including
March peak (8.9±2.9 vs. 7.1±1.9, p=0.007) and October lowest levels (7.2±2.2
vs. 5.9±1.5, p=0.009). Monthly decline in bilirubin occurred significantly more
in well nourished from March until October, when adjusted for NS (OR 11:
[1.2 – 102.9], p=0.02) and significantly increased more in malnourished from
October until December (OR 2: [1.07 – 3.7], p=0.044). Adjusted for NS, the Mean
corpuscular Volume decreased significantly more in January in well nourished,
OR 9.2: [2.1 – 39.5], p=0.003 and significantly increased in both groups in
December, with no difference between groups.
Conclusions: The seasonal pattern of bilirubin variations in dialysis pts seems
to be connected to variation of nutrition. The reduction of bilirubin in the
summer, resulting from better nutrition, might be amplified by the same sun
exposure seasonal pattern. The significant fall in bilirubin levels in January
in well-nourished patients, could be explained by increase in sun exposure.
In malnourished patients, this effect is overcome by insufficient food intakes
resulting in further increase of bilirubin until spring.
P180 (118)
PREDICTORS OF BONE MINERAL DENSITY (BMD) IN HEMODIALYSIS (HD)
PATIENTS
M. Młot-Michalska, A.E. Grzegorzewska
Chair and Department of Nephrology, Transplantology and Internal Diseases,
University of Medical Sciences, Poznan´ , Poland
Objectives: Mineral bone disease is a frequent complication in patients on
maintenance dialysis treatment which increases morbidity and reduces quality
of life. The aim of our study was to assess predictors of BMD in HD patients.
Methods: The study was performed in 60 patients treated with HD (26 women
and 36 men, age 54.8 ± 15.3 years, dialysis vintage 36.9 months, (range 6.0 –
279.6 months). BMD was measured in the femoral neck (FN) using dual-energy
x-ray absorptiometry. Associations/correlations between BMD and demographic
characteristics, anthropometric measurements assessing nutritional state, and
laboratory parameters of examined patients were analyzed.
Results: The best model for predictors of the FN BMD (0.813 ± 0.203 g/cm2)
in HD patients, built on the stepwise regression analysis (corr. R2 = 0.979),
included blood pH (7.35 ± 0.06, BETA = 0.605, p = 0.000), metrical age (BETA
= -0.497, p = 0.000), lean body mass (59.6 ± 12.6 kg, BETA = 0.394, p = 0.000),
total iron binding capacity (209.2 ± 37.5 µg/dL, BETA = 0.372, p = 0.002), serum
creatinine level (8.10 ± 3.28 mg/dL, BETA = 0.177, p = 0.004) and presence
of bone pain (declared by 33 HD patients, BETA = -0.096, p = 0.002). The last
parameter was replaced in the next model (corr. R2 = 0.978) by bone alkaline
phosphatase (BALP) activity (30.3 ± 15.2 U/L, BETA = -0.131, p = 0.005). The FN
BMD showed linear correlation with age (r = -0.591, p = 0.000), BALP activity (r =
-0.350, p = 0.007), serum creatinine (r = 0.316, p = 0.014), osteoprotegrin (11.15
± 5.41 pmol/L, r = -0.263, p = 0.043) and iron (83.1 ± 38.7 µg/dL, r = 0.277, p
= 0.032) levels. In both models blood pH was the strongest predictor of the FN
BMD; association between these parameters was described by the equation:
the femoral neck BMD (g/cm2) = 5.9766x1/pH.
Conclusions: We expect better preservation of BMD in HD patients by more
rigorous treatment of abnormalities in parameters of acid-base balance,
nutritional status, calcium-phosphate and iron metabolism. In HD patients who
declare bone pain the FN BMD should be checked.
487
Int J Artif Organs 2010 ; 33 ( 7): 488
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P181 (112)
WILLINGNESS TO CONSIDER LIVING DONOR KIDNEY TRANSPLANTATION
IN HEMODIALYSIS PATIENTS
D. Mladenovska, A. Sikole, L. Trajceska, G. Selim, V. Amitov, N. Ivanovski
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: Despite the confirmed benefit of living donor kidney transplantation
(LDKT), many patients hesitate to pursue this treatment option. The possible
reasons are: donor’s health and wellbeing, fear of unknown, feeling of guilt, etc.
The objective of the study was to examine predictors of willingness to consider
LDKT in hemodialysis (HD) patients in our centre.
Methods: One hundred and eighty HD patients were approached to participate
in this cross-sectional study. Patients older than 70 years, those with psychiatric
disorders and severe concomitant diseases were excluded, leaving 142 eligible
patients. The psychosocial questionnaire was completed by 132 subjects.
Multivariate statistical analysis was conducted to analyze socio-demographic
factors, perceived health status, perceptions and information about living
donation as predictors of the willingness to consider LDKT.
Results: Of 132 participants, 57 (43%) were willing to accept LDKT, 14 (11%)
were unsure and 61 (46%) were unwilling. In univariate analysis, the willingness
correlated with a lower perceived risk for the donor, higher perceived benefit,
better perceived current health status, perception that it is appropriate to ask a
family member to donate, and higher level of information received about LDKT
(p=0.001, respectively for all the variables). Older age and lower education
correlated with a lower acceptance (p=0.001 and p=0.03, respectively). No
significant effects were seen for gender, ethnicity, socio-economic, marital and
living status, dialysis vintage and spirituality. In multivariate analysis, willingness
to accept LDKT independently and positively correlated with higher perceived
benefit (p=0.001), lower risk perception (p=0.02) and with more favorable
perception of the current health status (p=0.001).
Conclusions: In conclusion, the authors recommend the appropriate educational
interventions for the patients and the potential donors.
P182 (64)
Prealbumin as a nutritional marker in hemodialysis and
renal transplant patients
S. Chrysostomou
National and Kapodistrian University, Medical School of Athens, Athens, Greece
Objectives: Although prealbumin is known as a sensitive nutritional marker,
there is still a very little research evidence that confirms its reliability in
hemodialysis (HD) and renal transplant (RT) patients. The aim of this study is to
assess prealbumin in HD and RT patients and compare it with other biochemical
and anthropometric markers of nutritional status.
Methods: Serum prealbumin is measured in 84 HD patients and in 154 RT
patients. Renal transplant patients are divided into 3 groups, based on the
year of renal transplantation (1st year, 1st-2nd year and 3rd-10th year). Other
anthropometric, biochemical and hematological measurements are included
in this study. Demographic and clinical data are also recorded from all study
patients. The definition of malnutrition, for all biochemical nutritional markers
is based on Kidney Disease Outcomes Quality Initiative (K/DOQI) and for
anthropometric markers is based on WHO Consultation on Obesity.
Results: HD patients are significantly older than RT patients but no significant
difference is found for body weight, BMI and MAC. Prealbumin levels are
significantly higher in HD patients compared with RT patients. Gender, age
and presence of anemia, hypertension and diabetes do not significantly affect
prealbumin levels, in none of the two groups. Prealbumin levels are significantly
positive correlated with duration of dialysis in the HD group and significantly
positive correlated with albumin in the RT group. Furthermore, prealbumin
levels are significantly higher in the 1-2nd group compared with the 1st year
group whereas serum albumin, creatitine and body weight are not significantly
different between these two groups.
Conclusions: HD patients have higher levels of prealbumin compared with RT
patients but both groups are malnourished, based on K/DOQI. Prealbumin is a
more sensitive, independent and acute marker of nutritional status especially in
RT patients, compared with other nutritional markers.
488 © 2010 Wichtig Editore - ISSN 0391-3988
P183 (178)
DAILY SALT INTAKE AND OVERHYDRATION IN PATIENTS ON
HEMODIALYSIS
G. Severova-Andreevska, L. Trajceska, P. Dzekova, G. Selim, S. Gelev, V. Amitov,
A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: With a progressive loss of urine output, sodium and fluid restrictions
are vital to control the extra cellular volume in anuric and oliguric patients (pts)
on hemodialysis (HD). Reducing the sodium load from their diet to 5–6 g salt,
appears to be sufficient to suppress thirst, despite the excessive weight gain
and overhydration (OH). In anuric pts, each 8 g NaCl, requires 1 L of fluid intake
to maintain normal serum sodium. If interdialytic weight gain (IDWG) exceedes
4–4.5% of dry weight (DW), complication of OH can appear. The aim was to
investigate the influence of daily salt intake (DSI) on signs of OH in pts on HD.
Materials and Methods: In 75 pts on MHD, mean age 58.5 years, the DSI was
calculated using the formula: NaCl (g/day) = 8*serum Na (mmol/L)/140(mmol/L)
(mean weekly IDWG(Kg)*3/6.5). According to the median level of DSI, they were
divided into low and high DSI pts. The total body water (TBW) was calculated
using Watsons’ formula. Therefore pts were followed for 6 months and mean
monthly values for the hematocrit (Ht), IDWG and amounts of NaCl 20% given
during HD were noted. Approaching the DW, hypertension (HT) and night
dyspnea were also evaluated. Chest X-ray and heart ultrasound (HU) were
performed. The χ² test and multivariate linear regression model from the SPSS
statistic program were used.
Results: The median level of DSI was 12.14 g/day. When age and TBW were
also dichotomized by median levels, significantly higher DSI were found for age
OR 0.2: [CI 0.09 - 0.6], p = 0.009 and in pts with higher levels of TBW OR
6: [CI 2.16 – 16.75], p = 0.0001. The amounts of NaCl 20% given during HD,
approaching the dry weight after HD and collapses during the HD insignificantly
affected the DSI (p= 0.09; p= 0.169; p= 0.151, respectively). Powerful predictive
factors for DSI like Na 20% given on HD (p = 0.0001, b = 0.245) and total body
water (p = 0.0001, b = 0.312) were found.
Conclusions: Pts with high DSI have a higher risk of having more TBW. Older
pts run a high risk of larger DSI. Low and high DSI pts do not differ in clinical
signs for OH.
P184 (327)
Mesor analysis of 24 hour blood pressure monitoring is a
good predictor of preeclampsia in high risk patients
B. Gerasimovska Kitanovska, K. Zafirovska, S. Bogdanovska, Lj. Lozance
Department of Nephrology, University Clinical Centre, Skopje, R. Macedonia
Objectives: To evaluate whether MESOR analysis (Midline estimated statistic of
the rhythm) is a good predictor of preeclampsia.
Materials and Methods: 24 hour blood pressure monitoring was evaluated in
40 pregnant women (20 normotensive and 20 with preeclampsia) by the use
of MESOR analysis (with Chronolab 3.0 software) in 6 control points during
pregnancy (08th, 18th, 23rd, 28th, 32nd, 36th gestation week). Laboratory
analysis and Doppler of the placental artery were performed in all pregnant
women.
Results: In the subgroup of patients with preeclampsia, diastolic MESOR was
higher than in the normotensive subgroup, starting from 23rd week, but it did
not reach statistical significance (75±8 mmHg vs. 70±6 mm Hg), although the
difference became statistically significant in 32nd and 36th gestation week.
Diastolic MESOR was significantly higher in the group with one or more risk
factors (pre-existing hypertension, recurrent preeclampsia, positive family history
of hypertension) starting from 18th gestation week and had a positive predictive
value of 76. In multiple regression analysis in the subgroup with several risk
factors, MESOR, positive family history, uric acid and Doppler changes were
predictive of preeclampsia starting from 18th gestation week.
Conclusions: MESOR analysis may be a good predictor of preeclampsia in the
high risk group.
Int J Artif Organs 2010 ; 33 ( 7): 489
Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia
P185 (293)
SUCCESSFUL PREGNANCY IN A 43 YEAR-OLD WOMaN WHO UNDERGO
LONG-TERM HEMODIALYSIS
G. Selim1, O. Stojceva-Taneva1, S. Gelev1, N. Stojcev1, V. Amitov1, G. Adamova2,
A. Sikole1
1
University Clinic of Nephrology; 2University of Obstetrics and Gynecology,
University “Sts. Cyril and Methodius”, Skopje, R. Macedonia
Pregnancy in hemodialysis (HD) patients is uncommon and associated with many
complications related to uremia or to comorbidities of chronic renal failure.
We report the case of a 43-year-old female patient, 10th gestational week with
three living offsprings (1988, 1990, 1993 year) and a history of five abortions
before 1988. During the first trimester of her 9th week's pregnancy (23.05.1996),
she developed placental abruption with peripartum hemorrhage, complicated
by fetal death and acute renal failure. Bilateral renal cortical necrosis was
documented in a contrast-enhanced CT scan, renal biopsy was not done for
the patient’s refusal and the patient was diagnosed as a case of ESRD in July
1996 year. She was maintained on HD 3 times a week since that time, with no
significant problems.
Six years after maintenance HD (2002), she presented with abdominal distension
and amenorrhea, she was found to be 16 weeks' pregnant, amniocentesis
testing was not done for the patient’s refusal. During pregnancy the HD schedule
was increased to 4 hours 4 times weekly between 16 to 23 week, 5 times weekly
between 24 to 28 week and 6 times weekly after 28 week of pregnancy. As a
consequence, pre-dialysis blood urea levels decreased from 22.1 mmol/L (20th
week), 17.7 mmol/L (24th week), 15.6 mmol/L (28th week) to 14.4 mmol/L at the
end of pregnancy. As expected, erythropoietin requirements were increased,
from a weekly dose of 8000 to a mean of 12000 units, but hemoglobin level
ranged between 90 and 72gm/L. Blood pressure increase was controlled by
alpha methyldopa, and using the ambulatory blood pressure monitoring was
119/76 mmHg (20th week and 28th week). On the 33th week of gestation, the
patient had a caesarean section delivery of a living boy weighing 2100 g. Patient
and boy remain healthy eight years after.
Our case illustrates that intensified dialysis regimens and attentive medical care
results in a successful outcome of pregnancy in HD patients.
P186 (294)
A MULTI-BIOMARKER APPROACH FOR THE PREDICTION OF
CARDIOVASCULAR MORTALITY IN HEMODYALISIS PATIENTS
G. Selim, O. Stojceva-Taneva, S. Gelev, N. Stojcev, P. Dzekova, L. Trajcevska,
A. Asani, I. Busletic, S. Pavleska, A. Sikole
University Clinic of Nephrology, University “Sts. Cyril and Methodius” Skopje,
R. Macedonia
In patients with end-stage renal disease, the ability of multiple biomarkers
monitoring to predict mortality has not been well established. This study
determined the prognostic value of multiple biomarkers for all-cause and
cardiovascular (CV) mortality in hemodialysis (HD) patients.
We measured brain natriuretic peptide (BNP), N-terminal pro-B-type natriuretic
peptide (NT-proBNP) and C-Reactive Protein (CRP) concentration, before HD in
125 prevalent HD patients (age 48.80±14.95 years and HD vintage 99.26±60.77
months) to examine the all-cause and CV mortality.
During the 2-year follow-up, 28 out of 125 patients (22.5%) had died, most
from CV diseases (65.7%). Patients who died of CV causes had higher
levels of BNP (3736.61±6239.16 vs.1112.08±1132.13; p=0.000), NT-proBNP
(17.004.56±10.549.00 vs. 8959.30±9509.74; p=0.025) and CRP (16.33±10.93
vs.7.44±6.88; p=0.000), as well as patients who died of all causes had higher
levels of BNP (2947.86±5178.76 vs 1105.35±1136.64; p=0.001), NT-proBNP
(14873.43±11588.36 vs. 717.67±9109.49; p=0.011) and CRP (14.68±1.54 vs.
8.49 ±8.09; p=0.004). The cut-off point for BNP, as predictor of the clinical
outcome, according to the ROC curve was 1200pg/mL for CV mortality
(sensitivity of 63% and specificity of 65%, AUC - 0.612, CI95%0.473-0.750)
and 10.000mg/L for NT-proBNP (sensitivity of 67.5% and specificity of 72.5%,
AUC-0.747, CI95%0.677-0.816). Kaplan-Meier analysis showed that all cause
(log rank, p=0.002; p=0.040; p=0.000) and CV mortality (log rank, p=0.001;
p=0.006; p=0.001) were the cause for a significantly lower survival in patients
with BNP>1200pg/mL, NT-proBNP>10.000 pg/mL and CRP>10mg/L.
Measuring the plasma concentration of the multiple biomarkers, particularly
CRP>10mg/L, as a marker of inflammation, BNP>1200pg/mL and NT-
proBNP>10000pg/mL, as markers of cardiac dysfunction, may be useful for the
identification of HD patients at high risk of CV mortality.
© 2010 Wichtig Editore - ISSN 0391-3988
P187 (217)
Hospital-Acquired Acute Kidney Injury Requiring Dialysis,
Does Age Matter?
P. Kes, N. Bašic´-Jukic´, B. Brunetta-Gavraniic´
Department of Dialysis, University Hospital Centre, Zagreb, Croatia
Hospital-acquired acute renal injury (HAARI) requiring dialysis is a known
complication in elderly patients. We compared incidence, etiology and outcome
of patients with HAARI requiring renal replacement therapy (RRT) according to
age difference. During 1-year prospective study, 62.951 consecutive patients
admitted to Univ. Hosp. Centre Zagreb were followed up for development of
AKI requiring RRT. Dialysis was instituted when patient exhibited inadequate
urine output for several hours despite correction of hemodynamic status and
diuretic therapy. Decision about type of dialysis treatment was made according
to patient hemodynamic stability and it was either daily hemodialysis or one
of continuous renal replacement therapies. Patients were divided into two
age categories: ≤64, and ≥65 years. 71 patient developed HAARI requiring
dialysis (0.11% of all patients hospitalized during the study period). First group
comprised 29 patients (40.9% of all HAARI patients; age 18-64 years) and
second comprised 42 patients (59.2%; age 65-90 years). There was significantly
higher incidence of arterial hypertension (31% vs. 73.8%) and mild CRF (24.1%
vs. 47.6%) among elderly patients. Incidence of diabetes mellitus (24.1% vs.
38.1%) and days of hospitalization when RRT was started (17.4 vs. 16.8) did not
differ significantly. The most common primary causes of HAARI were the same
in both groups. First was sepsis (67.9% younger and 61.0% elderly patients)
followed by ischemia (21.4% and 24.4%, respectively), and iatrogenic causes
such as ACEi, NSAID or aminoglycosides (7.1% and 12.2%, respectively).
Elderly patients developed HAARI more often after surgical procedure (76.2%
vs. 58.6%), but difference was not significant. There was almost no difference
in survival rate (33.3% elderly vs. 34.5% younger patients) or incidence of
CRF among survivors (21.4% vs. 20% respectively). Elderly patients with AKI
have the same perspective for survival and renal function recovery as younger
patients.
P188 (145)
ACQUIRED RENAL CYSTS PREDICT LOWER ERYTHROPOIETIN
REQUIREMENTS IN DIALYSIS PATIENTS
G. Severova, L. Trajceska, P. Dzekova, V. Pusevski, S. Gelev, G. Selim, V. Amitov,
A. Sikole
University Clinic of Nephrology, Skopje, R. Macedonia
Objectives: Identification of predictors of hyporesponsiviness to erythropoietin-
stimulating agents (ESA) in hemodialysis helps improving anemia management
and reduces hemoglobin (Hb) level variability. ESA requirements show
substantial inter- and intra-patient variability. This study aimed to assess the
associated factors with the ESA dose requirements in dialysis patients (pts)
maintaining stable hemoglobin levels.
Methods: Short-acting ESA were used in anemia management. ESA dosage
(defined as mean weekly ESA dose per Kg body weight) was assessed in 110
stable dialysis pts maintaining Hb above 10.0g/dL, within 6 measurements in
one year. Pts on dialysis less than one year, suffering from acute infections and
bleedings were excluded. Presence of acquired renal cysts by ultarsonography
prior to the study was evaluated in all patients. Univariate and multivariate
analyses were performed.
Results: 110 dialysis pts were evaluated. Presence of secondary renal cysts
was found in 10 (9.1%) of patients, 7 patients (6, 4%) were treated with
angiotensin converting enzyme (ACE) inhibitors. In the univariate analysis
the male gender, lower age of participants and lower ferritin levels correlated
positively with higher ESA dosage, but lost significance in the multivariate
model. The use of ACE inhibitors was positively but insignificantly correlated
with ESA dosage (p=0.077). The multivariate analysis showed that higher ESA
dosage was associated with presence of lower urea reduction rate, (β=0.212,
p=0.000), higher dosage of iron (β =0.295, p=0.001), higher phosphorous levels
(β =0.216, p=0.002) and higher CRP (β =0.361, p=0.002). Presence of Adult
polycystic disease and secondary renal cysts independently predicted lower
ESA dose requirements (β=-0.286, p=0.001), (β=-0.340, p=0.001), respectively.
Conclusions: Dialysis adequacy, inflammatory and iron status are of extreme
importance for anemia management in dialysis pts. Pts prone to secondary
renal cysts formation require significantly lower doses of erythropoietin in
maintenance of Hb levels.
489
 Int J Artif Organs 2010 ; 33 ( 7): 490

Posters: XXXVII Annual ESAO Congress, 8-11 September 2010, Skopje - R. Macedonia

P189 (346)
Hypertension in Chronic hemodialysis patients in The Institute
of Nephrology - Struga
V. Kovaceska Savreska, A. Derebanova
Institute of Nephrology, Struga, R. Macedonia

In clinical practice HTA is a very important risk factor for cardiovascular and
cerebrovascular complications, and the leading cause of mortality in dialysis
patients. The Institute of Nephrology (Struga) is treating 215 patients on HD. 114
are patients on ambulatory HD treatment. Hypertension was found in 81 (71%) of
patients. This problem is even greater in 18% of patients with HTA and Diabetes.
HTA was controlled adequately with HD (controlled by Ultrafiltration) in only 49
(60.5%) of patients. In the other 32 hypertensive patients (39.5%), hypertension
is not only treated by hemodialysis. They are on regular antihypertensive
therapy (usually ACE-inhibitors and Calcium antagonists). These patients are
fully monitored by measuring blood pressure before each hemodialysis, during
hemodialysis every 30 minutes, and at the end of HD. In the interdyalisis period,
blood pressure is monitored by 24 hour ambulatory-BP-monitoring. Weight was
monitored before and after HD, BMI, abdominal obesity (waist circumference),
complete laboratory investigations, ECG, Echocardiography, fundoscopy, etc.
Treatment of hypertension in patients on hemodialysis has its own peculiarities,
which require an individual approach, and the education of our patients.

490 © 2010 Wichtig Editore - ISSN 0391-3988

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