Ain Shams Journal of Anesthesiology Vol 2-2; July 200911 Comparative study between cardioprotective effects of intermittent antegrade blood cardioplegia with terminal warm blood reperfusion ('hot-shot') versus intermittent antegrade blood cardioplegia in pediatric cardiac surgery Hussein H. Sabri FRCA, Samia I. Sharaf MD, Abla A. Saab MD, Mohammed Saleh MSc. Department of Anesthesiology, Intensive Care, and Pain Management, Faculty of Medicine, Ain shams University, Cairo Abstract: Backg round : Terminal warm blood cardioplegia (hot-shot), has been shown to enhance myocardial protection in adult cardiac surgery. The aim of current study is to evaluate terminal warm cardioplegic blood reperfusion compared to conventional reperfusion to determine whether it has a beneficial cardioprotective effect during pediatric cardiac surgery. Metho ds: This prospective study was carried out in Ain Shams University Hospital on sixty children scheduled for pediatric cardiac surgery. Patients were randomly allocated into 2 equal groups: Control group (C): 30 patients received intermittent antegrade cold blood cardioplegia. Hot-shot group (HS): 30 patients received intermittent antegrade cold blood cardioplegia with terminal warm blood reperfusion just before declamping. We traced and compared the effect of warm cardioplegic blood reperfusion versus conventional reperfusion on clinical outcome paramet ers, myocar dial oxyge n and lactate ext racti on ratio afte r declampi ng and serum level of cardiac troponin I. Resu lts: This study demonstrated higher percentage of spontaneous defibrillation into sinus rhythm in hot-shot group when compared to control group (76.7% versus 33.3% respectively), lower level of inotropic support required for weaning from CBP in hot-shot group when compared to control group (4.4±5.5 versus 10.5±6.5 respectively), lower level of inotropic support required in the ICU in hot-shot group when compared to control group ( 75.4±61.2 versus 122.5±103.2 respectively), less duration of inotropic support required in the ICU in hot-shot group when compared to control group (9.5±7.2 hours versus 14.9±11.8 hours respectively), Myocardial lactate extraction ratio was significantly elevated at all studied time interval in hot-shot group when compared to control group, lower level of Serum troponin I at 4 hours after declamping in -shot group when compared to control group (13.2±8.0 ng/ml versus 31.3±23.1 ng/ml), lower level of Serum troponin I at 8 hours after declamping in hot-shot group when compared to control group (10.0±5.8ng/ml versus 19.1±11.5ng/ml). Conclusions: This study demonstrated that: intermittent cold blood cardioplegia with terminal warm blood cardioplegia offered favorable effect on the clinical outcome parameters in term of higher percentage of spontaneous defibrillation into sinus rhythm and lower level of inotropic support, in comparison to intermittent cold blood cardioplegia. Moreover, intermittent cold blood cardioplegia with terminal warm blood cardioplegia accelerated recovery of aerobic metabolism and reduced the myocardial damage following ischemia / reperfusion injury. Keywords: terminal warm blood cardioplegia •Hot-shot • pediatric myocardial preservation.
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7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
11
Comparative study between cardioprotective effects
of intermittent antegrade blood cardioplegia with
terminal warm blood reperfusion (hot-shot) versus
intermittent antegrade blood cardioplegia in
pediatric cardiac surgery
Hussein H Sabri FRCA Samia I Sharaf MD Abla A Saab MD
Mohammed Saleh MSc
Department of Anesthesiology Intensive Care and Pain Management
Faculty of Medicine Ain shams University Cairo
Abstract
Background Terminal warm blood cardioplegia (hot-shot) has been shown to enhance
myocardial protection in adult cardiac surgery The aim of current study is to evaluateterminal warm cardioplegic blood reperfusion compared to conventional reperfusion to
determine whether it has a beneficial cardioprotective effect during pediatric cardiac
surgery Methods This prospective study was carried out in Ain Shams University
Hospital on sixty children scheduled for pediatric cardiac surgery Patients were
randomly allocated into 2 equal groups Control group (C) 30 patients received
intermittent antegrade cold blood cardioplegia Hot-shot group (HS) 30 patients
received intermittent antegrade cold blood cardioplegia with terminal warm blood
reperfusion just before declamping We traced and compared the effect of warm
cardioplegic blood reperfusion versus conventional reperfusion on clinical outcome
parameters myocardial oxygen and lactate extraction ratio after declamping and serum
level of cardiac troponin I Results This study demonstrated higher percentage of
spontaneous defibrillation into sinus rhythm in hot-shot group when compared to
control group (767 versus 333 respectively) lower level of inotropic support
required for weaning from CBP in hot-shot group when compared to control group
(44plusmn55 versus 105plusmn65 respectively) lower level of inotropic support required in the
ICU in hot-shot group when compared to control group ( 754plusmn612 versus 1225plusmn1032
respectively) less duration of inotropic support required in the ICU in hot-shot group
when compared to control group (95plusmn72 hours versus 149plusmn118 hours respectively)
Myocardial lactate extraction ratio was significantly elevated at all studied time
interval in hot-shot group when compared to control group lower level of Serum
troponin I at 4 hours after declamping in -shot group when compared to control group
(132plusmn80 ngml versus 313plusmn231 ngml) lower level of Serum troponin I at 8 hours
after declamping in hot-shot group when compared to control group (100 plusmn 58ngml
versus 191plusmn 115ngml) Conclusions This study demonstrated that intermittent cold
blood cardioplegia with terminal warm blood cardioplegia offered favorable effect on theclinical outcome parameters in term of higher percentage of spontaneous defibrillation
into sinus rhythm and lower level of inotropic support in comparison to intermittent
cold blood cardioplegia Moreover intermittent cold blood cardioplegia with terminal
warm blood cardioplegia accelerated recovery of aerobic metabolism and reduced the
myocardial damage following ischemia reperfusion injury
Comparison of cardioprotective effects Hussein Sabri et al
12
Introduction
In an era when essentially nocongenital heart defect is consideredinoperable Repair of congenital
heart defects is becoming morefrequent in neonates and infantsThus pediatric myocardial pro-
tection has become of great interestto cardiac anesthetists who should
tailor their myocardial protectivetechniques to protect the immaturemyocardium during global myo-cardial ischemia to permit a greater
safety in performing complex con-genital heart repairs
Despite major advances in the
technical aspects of surgical repairof congenital heart diseases peri-
operative myocardial damage withlow cardiac output remains themost common cause of morbidityand death after repair of congenitallesion (Allen 2004) Cardiac
damage from inadequate myo-cardial protection can prolong
hospital stay and result in delayedmyocardial fibrosis leading to
cardiac dysfunction months to years
later So optimal myocardialprotection is as important as anexcellent technical repair inachieving the best long-term
outcome with surgical correction
Advances in cardioplegic techni-ques include intermittent ante-
grade cold blood cardioplegia withterminal warm blood reperfusion(hot-shot) that has been shown toenhance myocardial protection inadult cardiac surgery (Teoh et al
1986 Caputo et al 1998)
However because of structuralfunctional and biochemical diff-
erence in myocardial metabolismand response to ischemia andreperfusion cardioprotective stra-tegies should not be extrapolated to
pediatric cardiac practice withoutevident base (Toyoda et al 2003
Modi et al 2004)
The aim of the current study is
to evaluate the cardioprotectiveeffects of intermittent antegradecold blood cardioplegia withterminal warm blood cardioplegicreperfusion in pediatric cardiac
practice in comparison to inter-
mittent antegrade cold bloodcardioplegia
Patients and methods
After approval of both depart-ment of anesthesia faculty ofmedicine Ain Shams Universityand the medical ethics committeean informed consent was obtained
from the parents of each child
Methodology
Sixty children scheduled forpediatric cardiac surgery in AinShams University Hospital were
enrolled into this prospectiverandomized study Patients wererandomly allocated into two equalgroups Control group (C)
thirty patients submitted forcorrection of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
Study group [Hot-shot]
(HS) thirty patients submittedfor correction of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
with terminal warm cardioplegic
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
13
blood reperfusion just beforedeclamping of the aorta
The study population wasstratified based on clinical
diagnosis patients with right toleft shunt visualized by echo-cardiography were considered
cyanotic others considered non-cyanotic
Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion
criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation
Anesthetic management Anesthetic technique was stan-
dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively
Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed
Premedication Patients were
premedicated with oral midazolamat a dose of 05mgkg-1 given 15min
before induction of anesthesia tofacilitate quiet separation from theparents
Induction of anesthesia
Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a
peripheral venous cannula was
inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV
Ventilation was mechanically
controlled by Ohmeda 7800 venti-lator to deliver tidal volume of
10mlkg-1 respiratory rate wasadjusted achieve a partial pre-
ssure of carbon dioxide [PaCO2] of32-36mmHg
Monitoring On arrival to
operative theater patients were
monitored by electrocardiogram(lead II) pulse oximetry and non
invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was
inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular
Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Comparison of cardioprotective effects Hussein Sabri et al
12
Introduction
In an era when essentially nocongenital heart defect is consideredinoperable Repair of congenital
heart defects is becoming morefrequent in neonates and infantsThus pediatric myocardial pro-
tection has become of great interestto cardiac anesthetists who should
tailor their myocardial protectivetechniques to protect the immaturemyocardium during global myo-cardial ischemia to permit a greater
safety in performing complex con-genital heart repairs
Despite major advances in the
technical aspects of surgical repairof congenital heart diseases peri-
operative myocardial damage withlow cardiac output remains themost common cause of morbidityand death after repair of congenitallesion (Allen 2004) Cardiac
damage from inadequate myo-cardial protection can prolong
hospital stay and result in delayedmyocardial fibrosis leading to
cardiac dysfunction months to years
later So optimal myocardialprotection is as important as anexcellent technical repair inachieving the best long-term
outcome with surgical correction
Advances in cardioplegic techni-ques include intermittent ante-
grade cold blood cardioplegia withterminal warm blood reperfusion(hot-shot) that has been shown toenhance myocardial protection inadult cardiac surgery (Teoh et al
1986 Caputo et al 1998)
However because of structuralfunctional and biochemical diff-
erence in myocardial metabolismand response to ischemia andreperfusion cardioprotective stra-tegies should not be extrapolated to
pediatric cardiac practice withoutevident base (Toyoda et al 2003
Modi et al 2004)
The aim of the current study is
to evaluate the cardioprotectiveeffects of intermittent antegradecold blood cardioplegia withterminal warm blood cardioplegicreperfusion in pediatric cardiac
practice in comparison to inter-
mittent antegrade cold bloodcardioplegia
Patients and methods
After approval of both depart-ment of anesthesia faculty ofmedicine Ain Shams Universityand the medical ethics committeean informed consent was obtained
from the parents of each child
Methodology
Sixty children scheduled forpediatric cardiac surgery in AinShams University Hospital were
enrolled into this prospectiverandomized study Patients wererandomly allocated into two equalgroups Control group (C)
thirty patients submitted forcorrection of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
Study group [Hot-shot]
(HS) thirty patients submittedfor correction of congenital heartdisease and received intermittent
antegrade cold blood cardioplegia
with terminal warm cardioplegic
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
13
blood reperfusion just beforedeclamping of the aorta
The study population wasstratified based on clinical
diagnosis patients with right toleft shunt visualized by echo-cardiography were considered
cyanotic others considered non-cyanotic
Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion
criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation
Anesthetic management Anesthetic technique was stan-
dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively
Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed
Premedication Patients were
premedicated with oral midazolamat a dose of 05mgkg-1 given 15min
before induction of anesthesia tofacilitate quiet separation from theparents
Induction of anesthesia
Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a
peripheral venous cannula was
inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV
Ventilation was mechanically
controlled by Ohmeda 7800 venti-lator to deliver tidal volume of
10mlkg-1 respiratory rate wasadjusted achieve a partial pre-
ssure of carbon dioxide [PaCO2] of32-36mmHg
Monitoring On arrival to
operative theater patients were
monitored by electrocardiogram(lead II) pulse oximetry and non
invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was
inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular
Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
13
blood reperfusion just beforedeclamping of the aorta
The study population wasstratified based on clinical
diagnosis patients with right toleft shunt visualized by echo-cardiography were considered
cyanotic others considered non-cyanotic
Inclusion criteria Patients ofboth sexes presented for electiverepair of congenital heart diseaseBody weight 10-25kg Age12month-36month Exclusion
criteria Patients underwentpalliative operation (eg shuntpulmonary artery banding) andpresented for total repair Patientsunderwent previous repair andpresented for redo operationPatients on preoperative inotropicsupport Patients on preoperativemechanical ventilation
Anesthetic management Anesthetic technique was stan-
dardized for all patients Childrenshould have no milk formula orsolids for 6hrs prior to surgeryClear liquids are allowed up to 3hours preoperatively
Preoperative assessment After careful history taking a tho-rough physical examination wasdone This included assessment ofthe general condition chest exami-nation and measurement of axi-llary temperature Laboratorystudies chest x-ray and results ofechocardiography and catheteri-zation studies were reviewed
Premedication Patients were
premedicated with oral midazolamat a dose of 05mgkg-1 given 15min
before induction of anesthesia tofacilitate quiet separation from theparents
Induction of anesthesia
Anesthesia was induced withinhalation of halothane 2-3 in100 oxygen by face mask till a
peripheral venous cannula was
inserted and secured Then ane-sthesia was completed throughfentanyl 2microgkg-1 IV Trachealintubation was facilitated withpancuronium 01mgkg-1 IV
Ventilation was mechanically
controlled by Ohmeda 7800 venti-lator to deliver tidal volume of
10mlkg-1 respiratory rate wasadjusted achieve a partial pre-
ssure of carbon dioxide [PaCO2] of32-36mmHg
Monitoring On arrival to
operative theater patients were
monitored by electrocardiogram(lead II) pulse oximetry and non
invasive blood pressure Immed-iately after anesthetic inductionleft radial arterial catheter was
inserted after modified Allenstest for invasive blood pressuremonitoring and arterial bloodsampling Right internal jugular
Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Comparison of cardioprotective effects Hussein Sabri et al
14
blood gas acid base andelectrolytes analysis to correctany change in the ventilationelectrolytes or acid base balance
of the patient Maintenance of anesthesia
Anesthesia was maintained by
isoflurane 02-04 in 50 oxygen
air mixture extra analgesia wasprovided by fentanyl 10microgkg-1 IVbefore sternotomy in incrementsPancuronium in a dose of002mgkg-1 IV was used as
increment for adequate muscle
relaxation Management of cardio-
pulmonary bypass Immediately
after anesthetic induction activatedclotting time (ACT) was measuredand used as a control Anti-coagulation was achieved byadministration of heparin sulphate
3mgkg-1 IV and adjusted tomaintain ACT more than 480seconds Priming of Cardiopul-monary bypass (CPB) circuit
consisted of ringer solution
manifold sodium bicarbonate andblood or plasma depending oninitial hematocrit CPB wasestablished between ascending
aortic and bicaval cannulation CPBwas instituted using non-pulsatileflow ranging between 100-150mlkg-1min-1 to maintain mean
arterial pressure between 40-60mmHg
At full flow of CBP mecha-nical ventilation was stopped and
the lungs remained collapsed atthe functional residual capacityModerate systemic hypothermiawas used [28degC-32degC] Alpha stat
strategy for pH management wasadopted Hematocrit was main-tained above 25
Protocol of myocardial pro-tection In control group (C) Myo-
cardial protection was achievedwith intermittent antegrade coldblood cardioplegia with topicalheart cooling in all patients
Cardioplegic solution of 20mLKg-1
of body weight was initially infusedinto the aortic root after applicationof aortic cross clamp to achieve
cardiac arrest with subsequent
doses every 20min Blood cardio-plegia was prepared by mixingoxygenated blood with hyper-kalemic crystalloid solution in 11ratio with sodium bicarbonate
added as buffer lidocaine as mem-brane stabilizer and cooled to 9degC
[Table 1] [Table 2]
In hot-shot group (HS) Cardio-
plegic regimen was the same withan additional 20mLKg-1 of body
weight of warm (35degC) bloodcardioplegia was infused into the
aortic root just before declamping ofthe aorta The composition ofterminal warm blood cardioplegiawas the same as the cold blood
cardioplegia other than tempera-ture
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Myocardial lactate extractionrate ratio= [lactate A - lactate CS] x100lactate A
Lactate A serum lactate concen-tration in arterial blood sample
Lactate CS serum lactate concen-
tration in coronary sinus bloodsample
Serum level of cardiac
troponin I (cTnI) Two millilitersof blood sample collected fromeach patient after induction of
anesthesia and at 4 8hrs afterdeclamping of the aorta Bloodsamples were centrifuged and
stored at -20deg until the completionof the study when thawed once
and assays were performed by a
laboratory technician blinded tothe clinical status of the patientor their inclusion in the studySerum concentration of cardiac
troponin I was determined with acommercially available enzyme-linked immunosorbent assay
(ELISA) kits cTnI ELISA-DRG
international Inc
Principle of the test Sample
was allowed to react with themicrotiter coated with monoclonalanti troponin I antibody (solid
phase) Monoclonal anti troponinI-enzyme (horseradish peroxidase)conjugate solution was added
resulting in the troponin I molec-
ules being sandwiched between
the solid phase and enzyme-linked antibodies
A solution of tetramethyl-benzidine (TMB) reagent was added
and incubated for 20 minutesresulting in the development of ablue color The color development
was stopped with the addition of 1Nhydrochloric acid (HCl) changing
the color to yellow The concen-tration of troponin I was directlyproportional to the color intensity ofthe test sample Absorbance was
measured spectrophotometrically
using Dade Behring Inc BEPreg
IIIat wavelength 450nm
Statistical analysis
All data were prospectively
collected coded tabulated thensubjected to statistical analysisusing SPSSreg for Windows version150 software packages Numericalvariables were presented as mean
and standard deviation (SD) while
categorical variables were presen-ted as number of cases and percent
Between-groups comparisons of
numerical variables were performedwith unpaired student-t test whilethose of categorical variables wereperformed by Fisher exact test orChi-square test as appropriate For
all tests P-value of less than 005
was considered statistically signifi-
cantResults
Patientsrsquo characteristics and
intraoperative data The demog-
raphic data and patients pathology
were comparable in both studygroups as shown in (Table 3)
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Requirement of postoperative inotrope n () 24 (80) 14 (467) 0015
Inotrope score in ICU Meanplusmn SD 1225plusmn1032 754plusmn612 0036
Inotrope duration (h) Mean plusmn SD 149plusmn118 95plusmn72 0039
Duration of mechanical ventilation (h) Mean plusmn SD 88plusmn 44 67plusmn 38 0053
Duration of ICU stay (h) Mean plusmn SD 603 plusmn 231 511plusmn 188 0099
Mortality n () 3 (10) 0 (0) 0237
n () Number (percentage) of patients Mean plusmnSD P-value is significant when Plt005
unpaired t-test for inotrope score in ICU inotrope duration duration of mechanical Ventilation and duration of ICU stay P-value is significant when Plt005 Fisherrsquos exact test
for requirement of postoperative inotrope and mortality
Myocardial oxygen and lactate
extraction ratio As regards myo-
cardial oxygen extraction ratiothere was no significant differencebetween hot-shot group and
control group at the different
studied time intervals throughout
the initial sixty minutes ofreperfusion (P-value was gt005)(Table 6 Fig 1)
Table 6 Myocardial oxygen extraction ratio (MO2 ER)
Time interval after declamping of the aorta
Control
group
No =30
Hot-shot
group
No =30
P
value
M O2 ER immediately after declamping 529plusmn 62 512 plusmn 66 0308
M O2 ER 15 min after declamping 505plusmn 58 494 plusmn 61 0477
M O2 ER 30 min after declamping 492plusmn 55 480 plusmn 58 0414
M O2 ER 45 min after declamping 485plusmn 52 472 plusmn 55 0351
M O2 ER 60 min after declamping 476plusmn 51 468 plusmn 53 0554Mean plusmnSD P value is significant when P lt 005 unpaired t-test
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Comparison of cardioprotective effects Hussein Sabri et al
22
Serum level of cardiac troponinI (cTnI) There was no significantdifference between both studygroups as regards baseline values of
serum troponin I (P-value was0146) There was significantdifference between both study
groups in serum troponin I level at4 and 8 hours after declamping of
the aorta Serum troponin I level at
4 hours after declamping was132plusmn80ngml in hot-shot groupversus 313plusmn231ngml in controlgroup (P value was lt0001) Serum
troponin I level at 8 hours afterdeclamping was 100plusmn58ngml inhot-shot group versus 191plusmn115ngml in control group (P value waslt0001) (Table 8 Fig 3)
Table 8 Serum level of cardiac troponin I (cTnI)Control
group
No =30
Hot-shot
group
No =30
P
value
Baseline (ngml) 08plusmn
04 07plusmn
04 01464 hrs after declamping of the aorta (ngml) 313plusmn 231 132 plusmn 80 lt0001
8 hrs after declamping of the aorta (ngml) 191plusmn 115 100 plusmn 58 lt0001
Mean plusmn SD P-value is significant when P lt 005 unpaired t test
Fig 3 Serum level of cardiac troponin I (cTnI) Data are presented as mean Errorbars represent 95 confidence interval P value is significant when P lt 005
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
23
Discussion
Low cardiac output aftersurgically induced ischemia andreperfusion continues to be a major
contributor to morbidity andmortality after pediatric cardiacsurgery and in more than 50 of
cases has been attributed toinadequate myocardial protection(Bull et al 1984 Hammon
1995)
Careful control of theconditions of reperfusion and the
composition of the reperfusate can
optimize postischemic recovery ofmyocardial function (Follette et
al 1981 Allen et al 1986)
The current study wasdesigned to evaluate the cardio-protective effect of using inter-mittent antegrade cold bloodcardioplegia versus intermittent
cold blood cardioplegia with ter-minal warm blood cardioplegia
(hot-shot) in pediatric cardiacpatients
The result of the current
study demonstrated significantdecrease in blood pressure at 5and 15 minutes interval in thecontrol group compared with the
hot-shot group after weaning ofthe cardiopulmonary bypass
Intermittent cold blood
cardioplegia with terminal warmblood cardioplegia offers favorable
effect on the clinical outcomeparameters This was demon-strated in this study as asignificant higher percentage ofspontaneous defibrillation into
sinus rhythm in hot-shot group
than control group (767 versus333 respectively)
The percentage of patientsrequiring inotropic support after
weaning from cardiopulmonarybypass was significantly higher incontrol group than hot-shot group
(80 versus 467 respectively)
By adopting the inotropic scoredescribed by Wernovsky et al
(1995) the level of inotropic
support was significantly lower inhot-shot group than control group
(44plusmn55 versus 105plusmn65 respec-
tively)
The improved clinical outcomerevealed the role of intermittent
cold blood cardioplegia withterminal warm blood cardioplegia inenhancement of myocardialprotection which was manifested asa reduction in myocardial arrhyth-
mia associated with ischemiareperfusion and a better myocardial
functionThe myocardial protective effect
of terminal warm blood cardioplegia
extended into the postoperativeperiod This was manifested as asignificant higher percentage ofpatients in control group than hot-
shot group who required inotropicsupport in the intensive care (80
versus 467 respectively) The
maximum dose of inotropic support(calculated by a modification of
inotropic score) was significantlyhigher in control group than hot-shot group (1225plusmn1032 versus754plusmn612 respectively) Theduration of inotropic support was
significantly higher in control group
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Comparison of cardioprotective effects Hussein Sabri et al
24
than hot-shot group (149plusmn118versus 95plusmn72 respectively)
In the postoperative periodresults were comparable as
regards duration of mechanicalventilation and stay in theintensive care unit in addition to
comparable mortality rate
Myocardial oxygen extraction
ratio reflects balance betweenmyocardial oxygen supply anddemand Myocardial oxygenextraction ratio was similar
between the two studied groups
This similarity may reflect theaerobic metabolic state of the
myocardium provided by the coldblood cardioplegia in both groups
Lactate release from theischemic myocytes is considered asa reflection of anaerobic metabolism(Krause et al 1993)
A negative myocardial lactateextraction ratio indicates that
amount of lactate productionthrough anaerobic glycolysis washigher than the amount of lactate
consumption for aerobic energy pro-duction with continuing anaerobicmetabolism and impairment ofnormal aerobic energy production
While a positive myocardial
lactate extraction ratio indicatesthat amount of lactate production
through anaerobic glycolysis wasless than the amount of lactate
consumption for aerobic energyproduction and that myocardiumstarts to use lactate as a substratevia oxidative phosphorylation
Myocardial lactate extractionratio in control group stayednegative value all through the sixtyminutes of studied period which
indicates impairment of aerobicmyocardial metabolism during thisperiod In hot-shot group myo-cardial lactate extraction ratioremained negative value till 45min
after declamping of the aorta when
it becomes a positive value
This point is considered a turnfrom anaerobic to aerobic meta-
bolism and it resembles the equilib-
rium between lactate consumptionand production At this point themyocardium starts to use lactate as
a substrate via oxidative phosphor-rylation (Krause et al 1993)
The results of this studydemonstrate the recovery of aerobicmetabolism afforded by inter-
mittent cold blood cardioplegia withterminal warm blood cardioplegiaTroponin I is a myocyte-contractileapparatus protein released follo-
wing myocardial damage Troponin
I Level is considered sensitivemarker of myocardial injuryassociated with cardiac surgery
(Immer et al 1998)
In this study we demonstrated
a significant increase in post-operative troponin I at 4 8 hoursafter declamping of the aorta in
control group compared to hot-shotgroup (P value was lt0001) Thisreflects the beneficial effect of warmcardioplegic reperfusion on myo-cardial outcome in reducing themyocardial damage following
ischemiareperfusion injury
7262019 Comparative Study Between Cardioprotective Effects of Intermitternt Antegrade Blood Cardioplegia With Terminal hellip
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium
Ain Shams Journal of Anesthesiology Vol 2-2 July 2009
25
In this study the composition ofterminal warm blood cardioplegiawas made to resemble the compo-sition of cold blood cardioplegia
used The point was to provide asolution with adequate potassiumconcentration to produce electro-mechanical arrest during reper-fusion This solution differs from the
conventional blood reperfusate in
presence of high potassiumconcentration (20mmolL-1) ahigher pH and a higher osmolarity
Thus cardioprotective effect ofterminal warm blood cardioplegia is
expected to be achieved byprolongation of electromechanicalarrest which reduces the energy
demands and counteracting tissueacidosis and edema therefore it
reduces the myocardial injury bypreservation and resynthesis ofhigh energy phosphates
There were small number ofclinical studies that have
examined specific myocardialprotection strategy in pediatric
population Utilizing an isolatedblood perfused neonatal heartpreparation Nomura et al
(2001) assessed the effects of
terminal warm blood cardioplegiaterminal warm oxygenated crys-talloid cardioplegia in comparisonwith conventional reperfusion(without any kind of terminal
cardioplegia) through assessmentrecovery of left ventricularfunction They demonstrated that
reperfusion with either terminalwarm blood cardioplegia or ter-
minal warm oxygenated crys-talloid cardioplegia resulted in
better recovery of myocardialfunction with slightly betterfunction in terminal warm bloodcardioplegia
In a clinically relevant intactanimal model that simulated theclinical condition of hypoxic
neonatal myocardium exposed toischemic stress Kronon et al
(2000) investigated the cardio-
protective effects of terminalwarm blood cardioplegic reper-fusion versus conventional reper-
fusion through assessment reco-
very of left ventricular systolicfunction and diastolic complianceThey showed that A warm cardio-
plegic reperfusion helps reduce
the reperfusion injury resultingin improved myocardial functionand metabolic recovery in hypoxicneonatal myocardium