‫دراسة مقارنة بين استخدام المحلول المشل لعضلة القلب‬

‫الدافىء والبارد لحماية القلب فى مرضى قصور الشراين‬

‫التاجية مع ضعف متوسط فى عضلة القلب‬
‫رسالة مقدمة توطئة للحصول على درجة الدكتوراة فى جراحة القلب والصدر‬
‫مقدمة من‬
‫الطبيب‪ /‬أحمد محمد رضوان‬
‫ماجستير الجراحة العامة‬
‫كلية الطب – جامعة األزهر ‪2016‬‬
‫تحت إشراف‬

‫أ‪.‬د‪ /‬الحسينى الحسينى جميل‬

‫استاذ جراحة القلب والصدر‬

‫كلية الطب ‪ -‬جامعة االزهر‬

‫أ‪.‬د‪ /‬محمد الدسوقى شرع‬

‫استاذ مساعد جراحة القلب والصدر‬
‫كلية الطب ‪ -‬جامعة االزهر‬

‫د‪ /‬محمد حسينى محمود‬

‫مدرس جراحة القلب والصدر‬
‫كلية الطب ‪ -‬جامعة االزهر‬
‫جامعة األزهر‬
‫‪2017‬‬

‫‪1‬‬
Comparative study of warm versus cold cardioplegia
in myocardial protection in ischemic heart diseases
with moderate left ventricular systolic dysfunction.
Thesis
Submitted for Partial Fulfillment of MD
In Cardiothoracic surgery

By
Ahmed Mohammed Radwan
M.B.B.ch., MSc in general surgery
Faculty of Medicine, Al-Azhar University 2016
Supervised by

Prof. Dr. / El-Husseiny El-Husseiny Gamil

professor of cardiothoracic surgery
Faculty of Medicine, Al-Azhar University

Prof. Dr. / Mohamed El desoky Sharaa

Assistant professor of cardiothoracic surgery
Faculty of Medicine, Al-Azhar University

Prof. Dr. / Mohamed Husseiny Mahmoud

Lecturer of cardiothoracic surgery
Faculty of Medicine, Al-Azhar University
Al-Azhar University
2017

2
 Acknowledgement
Many thanks to Allah, who granted me the
ability to perform this essay

First and foremost,

I feel always indebted Allah, the most kind and

the most merciful, who guided and aided me to bring
this work to light. I would like to express my deepest
gratitude and sincerest thanks ProfDr/
Professor of Cardiothoracic surgery Faculty of
Medicine-Al-Azhar University as he gave me
privilege to work under his supervision a valuable
advices.

Words are not enough to express my greatest

thanks and deepest appreciations to Prof Dr. /

3
Faculty of Medicine -Al-Azhar University for his
comments, ideas, constrictive criticism and support
throughout this work.

List of content
Subject Page

Introduction& aim of the work 5

4
 List of abbreviations
ATP Adenosine tri-phosphate

BCP Blood cardioplegia

Ca+2 Calcium
CABG Coronary artery bypass grafting
CCP Crystalloid cardioplegia
CK Creatine kinase

CK-MB Creatine kinase-myocardial band

Cl− Chloride
CPB Cardiopulmonary Bypass
EF Ejection fraction
HCl Hydrochloride
ICC Intermittent hypothermic cardioplegia(cold)

ICU Intensive care unit

IHDs Ischemic heart disease

5
IWC Intermittent normothermic cardioplegia (warm)
K+ Potassium

MAP Mean arterial blood pressure

Mg2+, Magnesium

Mmol Millimole

MVR Mitral Valve Replacement Surgery

Na+2 Sodium
NADH Nicolinamide Adenine Dinucleoide Hydrogenase

NO Nitric oxide

NYHA New York Health Association classification

O2 Oxygen

PCO2 Partial pressure of carbon dioxide

PO2 Partial pressure of oxygen

ROS Reactive oxygen species

TV Tricuspid Valve

6
 Introduction
&
Aim of the work

7
 INTRODUCTION

Adequate protection of the myocardium is essential for

successful clinical outcome during cardiac surgery. Despite the large
number of experimental and clinical studies already conducted, the best
strategy for myocardial protection is still not established. (Giordano et
al., 2013)
There is no doubt that adequate myocardial protection plays
a key role in achieving successful outcomes in cardiac surgery Sending
the heart into a diastolic flaccid arrest requires understanding of the
underlying electrophysiology principles. Hyperkalemia (as the current
clinical practice either via blood cardioplegia or crystalloid cardioplegic
solution changes the cellular resting membrane potential of cardiac
myocytes towards a less negative value (i.e. closer to zero).
( Habertheuer et al., 2014)
Perioperative myocardial protection is an important
determinant for early and late outcome after cardiac surgery. Different
cardioplegic methods have been introduced, including different routes of

8
administration, different solution temperatures and a wide variety of
added substances. However, the two main types of cardioplegia
predominantly used are blood cardioplegia and crystalloid cardioplegia.
(Jonge et al., 2015)

The concept of myocardial protection during cardiac surgery

have been already described in detail in the 1950s by Bigelow, who
proposed to use hypothermia as a strategy to protect the myocardium in
heart surgery. In this respect, a reduction in myocardial oxygen
consumption up to 80 % can be achieved by lowering the blood
temperature up to 20 °C. However, the disadvantage of the isolated
hypothermia without an additional usage of cardioplegia results in an
incomplete electromechanical cardiac arrest with ventricular fibrillation.
(Zeriouh et al., 2015)
Therefore, subsequent studies by Gay and Ebert support the
use of potassium-rich solution for the induction of diastolic cardiac
arrest by depolarization. In addition, further development of blood
cardioplegia by Follette and Buckberg as a composition of blood and
crystalloid solution improved myocardial protection enormously.
Finally, the next breakthrough was the development of normothermic
blood cardioplegia in which Calafiore has set new standards in
myocardial protection during cardiac surgery. (Zeriouh et al., 2015)
Various strategies and combinations of techniques have been
used over the years, but two main techniques have been supported most:

9
the use of blood cardioplegia (BCP) and a crystalloid based solution.
Initially, crystalloid cardioplegia (CCP) was introduced as an agent to
allow for hypothermic hyperkalemic arrest. A large controversy persists
between the use of blood and crystalloid cardioplegia (CCP) in terms of
the benefits conferred to the heart by each . Antegrade cold CCP is the
simplest method of myocardial protection to implement. The quiet
bloodless field and flaccid heart provide optimal conditions for the
cardiac surgeon. Cardioplegic crystalloid solutions preserve ventricular
function, prevent depletion of high-energy substrates, and maintain
ultrastructural integrity. The advantages for BCP include oxygen
delivery, the buffering capacity of blood, capillary flow distribution
where red cells are essential, prevention of free radical generation,
maintenance of oncotic pressure and restriction of hemodilution. (Bruyn
et al., 2014)
Currently, a large variety of techniques for myocardial
protection is available in cardiac surgery. Most surgical centers in the
USA and west european countries preferably apply blood cardioplegia as
several studies indicated superiority of blood cardioplegia over
crystalloid solutions. Nevertheless, the debate over the optimal
cardioplegia strategy, the way of application and temperature is still
under discussion. Nowadays, the IWC as a simple and cost effective
method is in widespread use throughout the world. (Zeriouh et al.,
2015)

10
Cardioplegia
The intermittent cold crystalloid cardioplegia consisted of
Ringer’s solution (1000 ml) to which 1.6 mmol MgCl2, 1.6 mmol KCl,
0.1 mmol procaine-HCl and 2.5 ml sodium hydrogen bicarbonate were
added. The temperature of the cardioplegic solution was maintained at
4°C throughout the entire operative procedure. Warm intermittent blood
cardioplegia was composed by mixing one ampoule of 50 ml (containing
75 mmol K+, 12.5 mmol Mg2+, 100 mmol Cl−) with NaCl (0.9%). To
create 40 ml of blood cardioplegia, 20 ml of both solutions were mixed
in a syringe.13 The temperature of the cardioplegia was maintained at
physiological blood temperature (37°C) throughout the entire operative
procedure. (Jonge et al., 2009)
The basic concept which favored the use of warm blood
cardioplegia was that the oxygen (O2) consumption of the heart is
reduced to 90% below the baseline values when it is arrested by K+-
enriched normothermic blood, while there is only a slight reduction in
O2 consumption (7-8%) when the temperature is lowered to about 11°C.
Cold blood cardioplegia (10°C) protects the myocardium from ischemic
injury but inhibits mitochondrial respiration and raises coronary vascular
resistance, resulting in delayed recovery of postoperative ventricular
function. (Baig et al., 2015)

11
 The oxygen carrying capacity of blood is of great importance,
as oxygen is a substrate for ATP-production. Furthermore, using blood
cardioplegia, the production of lactate during ischemia is delayed.
(Yamamoto et al., 2009)

The use of blood was based on its superior oxygen-carrying

capacity, better osmotic properties and buffers, endogenous nutrients,
and antioxidants compared with its crystalloid counterpart, so use of
intermittent tepid blood cardioplegia for myocardial protection has
become more popular. (Yeh et al., 2003)

Some studies state that cold blood cardioplegia does not offer
better myocardial protection than a cold crystalloid solution does. (Sá et
al., 2009)

12
 Aim of the work

The objective of this study is to evaluate the safety ,efficacy and

outcome of warm blood cardioplegia with normothermic CPB, regarding
myocardial protection in ischemic heart diseases as compared to cold
crystalloid cardioplegia (CCC) with hypothermic CPB.

13
 Patients and methods

In the present study 60 patients with ischemic heart disease 30

patients of them will undergo IWC and 30 patients of them will undergo
ICC.

Statistical analysis will be performed using SAS (Statistical

analysis software) and values will be shown mean ± SD (standard
deviation), categoral analysis by X-square or Fisher's test.

Inclusion criteria

Patients with ischemic heart disease-1

Patient with or without mild and moderate degree of pulmonary - 2

hypertension

Patient with EF 35% to 45% -3

Exclusion criteria

1- Patient with severe degree of pulmonary hypertension

14
2- Patient with EF below 35%

3- Patient with EF above 45%

 Every patient will be subjected to:

A-Preoperative assessment
1) - History taking.
2) - Clinical examination.
3) - Chest X ray.
4) - Electrocardiography (ECG).
5) - Echocardiography describing detailed cardiac dimensions
and ejection fraction.
6) –Coronary angiography.

B- Intraoperative assessment
flaccid heart , baseline ECG
C- Postoperative assessment
1) - Full ICU monitoring (pulse, invasive and non-invasive blood
pressure, central venous pressures and urine output).
2) - ICU medications and need for inotropic support.
3) - Postoperative complications:

15
 * a. Postoperative Bleeding and Transfusion
b. Postoperative Myocardial Infarction and Low Cardiac Output
c. Postoperative Renal Dysfunction

d. Neurological Complications
e. Arrhythmias
f. Mortality
4) - Hospital stay.
5)- Early postoperative echocardiography before discharge from hospital
with assessment degree of residual EF .
6)-Early and late postoperative follow up and need of medical treatment.

16
References

17
 References
Andreas Habertheuer, Alfred Kocher, Günther Laufer, Martin
Andreas, Wilson Y. Szeto, Peter Petzelbauer, Marek Ehrlich, and
Dominik Wiedemann (2014): Cardioprotection: A Review of Current
Practice in Global Ischemia and Future Translational Perspective,
Hindawi Publishing Corporation BioMed Research International
Volume 2014, Article ID 325725, 11 pages

Chi-Hsiao Yeh, Yao-Chang Wang, Yi-Cheng Wu, Jaw-Ji Chu and

Pyng Jing Lin(2003): Continuous Tepid Blood Cardioplegia Can
Preserve Coronary Endothelium and Ameliorate the Occurrence of
Cardiomyocyte Apoptosis CHEST;123:1647–1654

Giordano, P., Scrascia, G., D’Agostino, D., Mastro, F., Rotunno, C.,
Conte, M., Rociola, R. and Paparella, D. (2013): Myocardial Damage
Following Cardiac Surgery: Comparison between Single-Dose Celsior
Cardioplegic Solution and Cold Blood Multi-Dose Cardioplegia.
Perfusion, 28, 496-502.

18
Helene De Bruyn, France Gelders, Tine Gregoir, Valerie Waelbers,
Pascal Starinieri, Jean-Louis Pauwels, Jeroen Lehaen, Boris Robic,
Alaaddin Yilmaz, Urbain Mees, Marc Hendrikx (2014): Myocardial
Protection during Cardiac Surgery: Warm Blood versus Crystalloid
Cardioplegia, World Journal of Cardiovascular Diseases, August, 4,
422-431

M de Jonge ,AG van Boxtel, MA Soliman Hamad, MM Mokhles, S

Bramer, RLJ Osnabrugge, AHM van Straten and E Berreklouw
(2015): Intermittent warm blood versus cold crystalloid cardioplegia for
myocardial protection: a propensity score-matched analysis of 12-year
single-center experience) Perfusion 2015, Vol. 30(3) 243–249

Mirza Ahmad Raza Baig, Muhammad Sher-I Murtaza, Azhar

Iqbal ,Muhammad Zubair Ahmad, Hafiz Muhammad Farhan Ali
Rizvi, Nosheen Ahmed, Alia Shair, AnumIjaz (2015): Clinical
outcomes of intermittent antegrade warm versus cold blood cardioplegia
J Pak Med Assoc 593:596 June Vol. 65, No. 6,

Mohamed Zeriouh, Ammar Heider, Parwis B. Rahmanian, Yeong-

Hoon Choi, Anton Sabashnikov, Maximillian Scherner, Aron-
Frederik Popov, Alexander Weymann, Ali Ghodsizad, Antje-Christin
Deppe, Axel Kröner, Ferdinand Kuhn-Régnier, Jens Wippermann and

19
Thorsten Wahlers (2015):Six-years survival and predictors of mortality
after CABG using cold vs. warm blood cardioplegia in elective and
emergent settings Zeriouh et al. Journal of Cardiothoracic Surgery
10:180.

Sá, M.P., Rueda, F.G., Ferraz, P.E., Chalegre, S.T., Vasconcelos, F.P.
and Lima, R.C. (2012) : Is There Any Difference between Blood and
Crystalloid Cardioplegia for Myocardial Protection during Cardiac
Surgery? A Meta-Analysis of 5576 Patients from 36 Randomized Trials.
Perfusion, 27, 535-546

Yamamoto, H., Magishi, K., Goh, K., Sasajima, T. and Yamamoto, F.

(2009): Cardioprotective Effects of Normothermic Reperfusion with
Oxygenated Potassium Cardioplegia: A Possible Mechanism. Interactive
Cardiovascular and Thoracic Surgery 9, 598-604

20
‫الملخص العربي‬

‫الملخص العربي‬
‫‪21‬‬
 ‫من الضرورى توفير الحماية الكافية لعضلة القلب اثناء جراحة القلب للحصول على النتائج‬
‫المرجوة من هذة الطرق المحلول المشل لعضلة القلب الذى يتوقف على تغير كهربية القلب‬
‫بزيادة البوتاسيوم وهناك طرق مختلفة للتحضير اما باختالف درجة حرارة المحلول او اختالف‬
‫‪.‬تركيب المحلول المستخدم فى التحضير اما دم او محلول بلورى‬

‫وقد هدف ذلك البحث إلى المقارنة بين طريقتين من طرق الحماية لعضلة القلب وهى استخدام‬
‫‪ .‬المحلول المشل بالدم الدافىء والمحلول البلورى البارد وكالهما غنى بالبوتاسيوم‬

‫‪ :‬حيث تمت الدراسة علي ‪ 60‬مريض تم تقسيمهم الى مجموعتين‬

‫‪:‬المجموعة األولى‬

‫وتشمل ‪ 30‬مريض تم استخدام المحلول المشل بالدم الدافىء لحماية عضلة القلب‬

‫‪:‬المجموعة الثانية‬

‫وتشمل ‪ 30‬مريض تم استخدام المحلول المشل البلورى البارد لحماية عضلة القلب‬

‫أوال ‪ /‬مرحلة ما قبل التدخل الجراحي‬

‫حيث تتم فيها عمل الموجات الصوتية للقلب لتحديد وظيفة القلب وكذلك قسطرة تشخصية لمعرفة‬
‫القصور الشريانى وعمل الفحوصات والتحاليل الالزمة لما قبل التدخل الجراحي‬
‫ثانيا ‪ /‬مرحلة التدخل الجراحي‬
‫حيث يتم فيها االطمئنان على عدم وجود انقبضات او تاثير كهربى للقلب‬
‫ثالثا‪ /‬مرحاة مابعد الجراحة مباشرة (الرعاية المركزة)‬
‫حيث يتم فيها مالحظة الوظائف الحيوية للمرضى وتقييم االدوية المنشطة لعضلة القلب و وعمل‬
‫فحص اكلينيكي وعمل موجات صوتية للقلب لمعرفة نتيجة اإلصالح في كال المجموعتين من‬
‫‪.‬المرضى‬

‫‪22‬‬