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Albumin
Albumin
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ORIGINAL ARTICLE
a
Department of Cardiovascular Surgery, Turkiye Yuksek Ihtisas Training and Research Hospital, Ankara,
Turkey
b
Department of Cardiovascular Surgery, Yildirim Beyazit Training and Research Hospital, Ankara, Turkey
c _
Department of Cardiovascular Surgery, Izzet Baysal University, Bolu, Turkey
d
Department of Cardiovascular Surgery, Necmettin Erbakan University, Konya, Turkey
Received 19 January 2013; received in revised form 16 July 2013; accepted 23 September 2013
Available online 7 November 2013
KEYWORDS Summary Background: In this study, we have tried to demonstrate the effects of coating
complement; style used in oxygenators on various hematologic and clinical parameters.
interleukin; Materials and methods: Twenty-seven patients were included in the study, who had under-
oxygenator; gone operations because of elective coronary artery disease. Albumin-coated oxygenator
systemic was used in Group I. In Group II, a synthetic polypeptide-coated oxygenator was used.
inflammatory C1-inhib (complement), C3c, C4, interleukins (IL-1b, IL2, IL-6, IL-10), and tumor necrosis
response syndrome factor alpha (TNF-a) levels were examined at four different time intervals. Hemoglobin, he-
matocrit, leukocyte and platelet counts, drainage, and transfused blood volumes were
analyzed.
Results: Albumin levels were significantly lower in Group I than those in Group II 5 minutes
after the removal of the cross-clamp. Twenty-four hours after the surgery, Group I patients
also had a significantly higher white blood cell count compared to Group II patients. TNF-a
levels in Group I were always expressed in considerably higher amounts than those in Group
II. IL-6 levels were significantly higher in Group I, but IL-10 levels were observed to be high-
er in Group II (p < 0.05).
Conflicts of interest: The authors declare that they have no financial or non-financial conflicts of interest related to the subject matter
or materials discussed in the manuscript.
* Corresponding author. Department of Cardiovascular Surgery, Yuksek Ihtisas Training and Research Hospital, Kızılay Street, Altindag,
Ankara, Turkey.
E-mail address: erdaldr@yahoo.com (E. Simsek).
1015-9584/$36 Copyright ª 2013, Asian Surgical Association. Published by Elsevier Taiwan LLC. All rights reserved.
http://dx.doi.org/10.1016/j.asjsur.2013.09.004
94 E. Simsek et al.
1. Introduction injection, reaching the peak value in 3-4 hours time. This
stimulates IL-6 expression. IL-1 injection induces tumor
Systemic Inflammatory Response Syndrome (SIRS) can be necrosis factor (TNF) expression in macrophages and IL-6
the result of coagulation system activation and inflamma- expression in fibroblasts.
tory reactions triggered by blood getting into contact with IL-2 is mostly secreted by T4 cells but, it can also be
nonbiological membranes during cardiopulmonary secreted by T-8 cells medullary thymocytes and giant
bypass.1,2 SIRS is characterized by hypotension, coagulop- granule lymphocytes. It leads to endothelial permeability
athy, free oxygen radicals production, and platelet pro- increase and leak syndrome due to the secretion of various
duction, which are significantly associated with morbidity cytokines.
and mortality. It is thought that endothelial damage and IL-6 is released by T and B lymphocytes, monocytes,
increased microvascular permeability may play a role in the endothelial cells, epithelial cells and fibroblasts. It is an
physiopathological mechanism of this syndrome.3 indicator of an acute inflammatory response. IL-6 level in
One of the most important immunological structures plasma rises proportionally to the tissue damage caused by
affecting the inflammatory reactions that develop after the surgeon and the inflammatory response induced by
cardiopulmonary bypass (CPB) is the complement system. CPB.
The severity of the complement response alters depending IL-10 inhibits TH1 (T helper lymphocytes) and natural
on the length of CPB4 and the circulation system used.5 cells’ cytokine production. It increases B cell proliferation
During CPB, not only the existence of C3a, C5a, and and antibody production and inhibits cellular immunity. By
membrane attack complex (MAC), but also the consumption inhibiting TNF-a and nitrous oxide (NO) production, endo-
of the complement components indicate the activation of gen IL-10 has a role in the protection of myocardium during
the complement system in the circulation.6 Considerable ischemic reperfusion.
complement activations occur within the first 3 days TNF is composed of two peptides called TNF-a and TNF-
following the CPB.7 During the bypass, the complement b. TNF-a is an endogenous pyrogen and an acute phase
system is activated by standard and alternative methods; reactant secreted by activated macrophages. TNF-a has
while the standard activation method leads to an increase role in local neutrophilic infiltration, tumor necrosis,
both in C3a and C4a, the alternative activation method cachexia, and neutrophilia, and it has radioprotective ef-
leads to an increase only in C3a.8 C3a begins to increase fects at the same time. TNF-a, like proinflammatory cyto-
with the start of CPB and reaches its peak at the end of the kines, may individually turn into potential harmful
bypass. C3a level depends on the length of the bypass and mediators, when their plasma levels increase
reverts back to its standard level after 48 hours. C5a is substantially.10
related to instant reperfusion. C5a triggers activated leu- Oxygenators are accused of causing hemolysis because
kocytes, therefore, increases superoxide production and of abrupt pressure changes and increased surface tension.
enables them to attach to the coronary artery Perfusion through an oxygenator increases platelet mem-
endothelium.9 brane fragility, leading to increased possibility of hemoly-
There exist important peptides that function in inflam- sis, which then decreases after a 24-hour period. Further
matory and repair roles in the regulation of an organism’s trauma to blood components can be caused by the aspira-
immunity system. These peptides are generally called cy- tion system.2 One of the accused tools leading to coagula-
tokines. Cytokines play a role in both systemic and local tion cascade activation and inflammatory responses is the
inflammation by regulating cell-to-cell communication. “oxygenator” and numerous attempts have been made to
These cytokines are functionally proinflammatory (IL-1, change its surface with the hope of preventing these
IL8) and anti-inflammatory [IL-1RA (IL-1 receptor antago- catastrophic events. Therefore, we investigated the effects
nist), IL-10]. IL-6 shows both characteristics. Proin- of coating style (albumin or synthetic peptide) used in ox-
flammatory cytokines such as IL-1a, IL-1b, and IL-6 may ygenators within various hematologic and clinical
turn out to be harmful mediators when plasma levels are parameters.
high in cases such as major trauma, sepsis, and shock.10 In
cardiac surgery, according to some observations, both pro 2. Materials and methods
and anti-inflammatory cytokines expression increase in
order to provide an equilibrium between them.11 Twenty-seven patients undergoing elective coronary artery
IL-1 has effects on the emergence of local neutrophil bypass grafting (CABG) were included in the study. Our
infiltration, delayed type cell sensitivity, fibroplasias, and exclusion criteria among the patients was as follows: any
angiogenesis. After IL-1 injection, local inflammatory anticoagulant, steroid or anti-inflammatory drug usage
response begins. This reaction starts 1 hour after the within the last 7 days prior to enrollment, previous bypass
Coated oxygenators and inflammatory response syndrome 95
surgery and anyone in need of additional surgical pro- TNF-a was studied by the ELISA method using immuno-
cedures. The patients were randomly allocated into two assay kits (BioSource International, Inc USA). The results
groups based on oxygenators used. In Group I, albumin- were obtained by using Biotek ELISA reader at 450 nm.
coated (Jostra REF VKMO 4230, Hirrlingen, Germany) Hemoglobin, hematocrit, leukocyte, and platelet counts
oxygenator was used (n Z 14, male:female ratio Z 10:4, were analyzed with a Coulter Max M mode device. More-
mean age Z 58 8 years), and in Group II, a synthetic over, we also used an Olympus AU 5200 machine for
peptide-coated oxygenator (Jostra REF VKMO 4200, Hirr- determining total protein and albumin levels.
lingen, Germany) was used (n Z 13, male:female Z 10:3, Drainage and transfused blood volumes were recorded at
mean age Z 58 10 years). 4-hour intervals at 0, 8, and 12 hours postoperatively.
A radial artery and a central vein were cannulated in all
patients. Pentothal sodium 3e4 mg/kg, cisatracurium 2.1. Statistical analysis
(Nimbex) 0.15e0.2 mg/kg and fentanyl were used for
anesthesia induction. Thereafter, fentanyl (100 mg) and
Variables were expressed as a mean for standard deviation.
Nimbex (0.02 mg/kg with 30-minute intervals) were used
To compare groups, Student t test and Mann-Whitney U test
for anesthesia. Intravenous heparin (5 mg/kg) was given for
were used according to the normality test results assessed
systemic heparinization, which was neutralized with prot-
by Kolmogorov-Smirnov test. A p value less than 0.05 was
amine sulfate following the cessation of extracorporeal
considered as significant.
circulation. We preferred isothermic blood cardioplegia and
abstained from steroid drugs during the surgery. In the case
of a low preoperative hemoglobin level, erythrocyte sus- 3. Results
pension was added to the individual patient’s prime volume
(Isolyte S 1000 mL, Gelofusine 500 mL, mannitol 100 mL, There were no statistically significant differences between
heparin 50 mg, 3 ampule NaHCO3, antibiotic). Blood sam- the groups in terms of age, gender, body surface area,
ples were taken from radial artery at the following time cross-clamp time, body temperature during bypass, he-
points: matocrit, and drainage volumes corrected by time and
transfusion requirements (Table 1).
T1: Following anesthesia induction, just before surgical Total protein, hematocrit, and platelet count values
incision. were similar in both of the groups at the same intervals.
T2: 5 minutes after the removal of cross-clamp. Albumin levels were significantly lower in Group I at time 2
T3: At 6th hour from the start of CPB surgery. (Table 2). Group I patients had also significantly higher
T4: At 24th hour from the start of CPB surgery. white blood cell count 24 hours after surgery.
Postoperative total protein, albumin, hematocrit, and
The blood taken in flat test tubes was allowed to stand platelet counts were significantly lower, and white blood
at þ4 C until it became decomposed with a 10-minute cell counts were significantly higher in both of the groups.
centrifugation in 3000 rotation. The decomposed sera were C1, C3, and C4 checked at four different intervals had no
kept at 70 C in a deep freeze. C1inhib, C3c, and C4 were statistical difference in both groups (p > 0.05). While C1,
studied using the nephelometric method with a Behring C3, and C4 prominently decreased in surgery, a slight in-
Nephelometer Analyzer device, and the results were indi- crease was observed following CPB (Fig. 1).
cated in terms of g/dL. Statistical comparisons and levels of cytokines between
IL-1b, IL2, IL-6, and IL-10 were studied by the ELISA Group I and Group II are shown in Table 3. Regarding Group
method using immunoassay kits (BioSource International, II, the increase of TNF-a in T1eT3 was significant
Inc USA). The results were obtained by using a Biotek ELISA (p < 0.05), while the decrease in T3eT4 was not significant
reader at 450 nm and interleukin results were calculated as (p > 0.05). In Group I, the increase of TNF-a in T1eT3 was
picograms (pg)/mL. very significant (p < 0.01), while the increase in T1eT4 was
Table 1 Statistical comparison of demographic and operational variables in Group I and Group II.
Group I Group II p
Age (y) 58 8 58 10 NS
Sex 4 females, 10 males 3 females, 10 males NS
BSA (m2) 1.84 0.14 1.91 0.15 NS
Duration of pump (min) 69.28 35.37 78.38 23.8 NS
Duration of cross clamping (min) 39.4 21.8 43.3 13.6 NS
Temperature ( C) 29.28 2.19 29.23 1.3 NS
HTC in CPB (%) 21.5 3.34 23.76 3.72 NS
0e4 h drainage (mL) 338.8 244 266.9 167 NS
4e8 h drainage (mL) 155.7 75.7 132.6 104.2 NS
8e12 h drainage (mL) 91.15 104.16 105.7 109.5 NS
Post-operative blood transfusion (unit) 1 1.22 0.61 1.19 NS
BSA Z body surface area; CPB Z cardiopulmonary bypass; HTC Z hematocrit; NS Z not significant.
96 E. Simsek et al.
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