You are on page 1of 6

Journal of the Egyptian Society of Cardio-Thoracic Surgery xxx (2017) 1e6

H O S T E D BY Contents lists available at ScienceDirect

Journal of the Egyptian Society of Cardio-Thoracic Surgery


journal homepage: http://www.journals.elsevier.com/journal-of-
the-egyptian-society-of-cardio-thoracic-surgery/

Effect of terminal warm reperfusion (hot shot) and remote


ischemic preconditioning, either separately or combined, on
myocardial recovery in adult cardiac surgery
Mohamed Elgariah, Mohamed Abo El Nasr*, Hosam Fawzy, Ehab Wahby,
Abdelhady Taha
Department of Cardiothoracic Surgery, Faculty of Medicine, Tanta University, Egypt

a r t i c l e i n f o a b s t r a c t

Article history: Background: Reperfusion injury is a major contributor to morbidity and mortality after
Received 4 June 2017
cardiac surgery. Among the myocardial protective modalities, terminal warm reperfusion
Received in revised form 13 July 2017
(hot shot) and remote ischemic pre-conditioning techniques were found to protect
Accepted 21 July 2017
Available online xxx myocardial function and improve better postoperative outcomes. The aim of this study was
to compare the effect of terminal hot shot cardioplegia, the effect of remote ischemic
preconditioning and the effect of both techniques on myocardial recovery after adult
Keywords:
Myocardial protection cardiac surgery.
Cardioplegia Methods: One hundred forty-five patients were divided into four groups comparing hot
Hot shot shot group, remote ischemic preconditioning group, combined hot shot and remote
Remote ischemic preconditioning ischemic preconditioning group and the control group. The data collected included pre-
operative demographic and clinical characteristics, intraoperative data and postoperative
short term outcome including inhospital mortality.
Results: Patients of the combined group were found to have significantly better outcome
including fewer ventricular arrhythmias, less intra-operative need of intra-aortic balloon
pump, low cardiac output, and less length of ICU stay. The in-hospital mortality showed a
significant difference between the 4 groups. Among patients without hot shot, the inci-
dence of postoperative temporary epicardial pacing was higher and decreased in patients
underwent hot shot and remote ischemic preconditioning but didn't reach a statistical
significance.
Conclusions: Both remote ischemic preconditioning and terminal hot shot reperfusion
before removal of the aortic cross clamping improved outcome of on-pump adult cardiac
surgery patients. There was a significant effect on the in-hospital mortality and there were
fewer incidences of arrhythmias and less requirement for postoperative inotropic support
with this technique.
© 2017 Publishing services by Elsevier B.V. on behalf of The Egyptian Society of Cardio-
thoracic Surgery. This is an open access article under the CC BY-NC-ND license (http://
creativecommons.org/licenses/by-nc-nd/4.0/).

* Corresponding author.
E-mail address: dr_mmaboelnasr@yahoo.com (M. Abo El Nasr).
Peer review under responsibility of The Egyptian Society of Cardio-thoracic Surgery.

http://dx.doi.org/10.1016/j.jescts.2017.07.005
1110-578X/© 2017 Publishing services by Elsevier B.V. on behalf of The Egyptian Society of Cardio-thoracic Surgery. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Please cite this article in press as: Elgariah M, et al., Effect of terminal warm reperfusion (hot shot) and remote ischemic pre-
conditioning, either separately or combined, on myocardial recovery in adult cardiac surgery, Journal of the Egyptian Society of
Cardio-Thoracic Surgery (2017), http://dx.doi.org/10.1016/j.jescts.2017.07.005
2 M. Elgariah et al. / Journal of the Egyptian Society of Cardio-Thoracic Surgery xxx (2017) 1e6

1. Introduction

Even though advances in surgical technique, anesthesia, myocardial protection and postoperative care have reduced the
risk involved in open heart surgery; compromised ventricular function and arrhythmias still occur in cardiac surgery patients
[1].
Cardiac surgeons and anesthesiologists have sought more optimal methods to protect the myocardium from ischemia-
reperfusion injury. It has been well established that antegrade cardioplegia may fail to give adequate protection to all
myocardial regions [2]. Retrograde cardioplegia has been proposed as an alternative or additive to antegrade cardioplegia [3],
but studies showed that combined delivery of cardioplegia did not provide adequate myocardial protection especially in
coronary artery disease cases [4e7]. Thus, consideration of additional myocardial protection strategies is necessary.
Advances in cardioplegic techniques included intermittent antegrade cold blood cardioplegia with terminal warm
reperfusion (hot-shot) which has been shown to improve myocardial protection in open heart surgery [8]. Terminal Warm
reperfusion (hot shot) refers to the administration of terminal warm perfusate before removing the aortic cross clamp aiming
to wash out anaerobic metabolites from the coronary circulation of the arrested heart and to minimize the ischemia-
reperfusion myocardial injury and to achieve resumption of effective electro-mechanical myocardial activity [9].
Remote ischemic preconditioning depends on protection of the heart by applying repetitive ischemia and reperfusion to
an organ remote from the heart. Ischemic preconditioning was first described by Przyklenk et al. [10], who found that the size
of myocardial infarction due to left anterior descending artery occlusion was reduced after intermittent occlusion of
circumflex artery. This idea was taken and extended to investigate the effect of ischemic stimulus to an organ remote from the
heart on myocardial protection [11e14].
We aimed to compare the effect of terminal hot shot cardioplegia, the effect of remote ischemic preconditioning and the
effect of both techniques on myocardial recovery after adult cardiac surgery.

2. Patients and methods

2.1. Study population

One hundred forty-five patients who underwent either valve surgery or coronary artery bypass grafting (CABG) at
Cardiothoracic Surgery Department in Tanta University Hospital, Tanta, Egypt between December 2014 and December 2016
were enrolled in this study. Data were prospectively collected and analyzed. The study population was adult cardiac surgery
patients who were electively scheduled for valve surgery or CABG. Patients were divided into four groups comparing first
group (control group), the second group (Hot shot group) and the third group (remote ischemic preconditioning (RIPC) group)
and the fourth group (combined group). Informed consent was taken from patients involved in the study. The protocol was
approved by the Tanta faculty of medicine ethical committee.

2.2. Outcome measures

2.2.1. Intraoperative variables included


The time needed by the heart from aortic declamping to restoration of effective electro-mechanical contraction, the heart
rate and rhythm after aortic declamping, the occurrence of ST-segment changes in the ECG, the mean arterial blood pressure,
the arterial blood pH changes, the need for defibrillation and the response, the need for inotropic support, the need for anti-
arrhythmic drugs, the need for artificial pacing, the need for reentry to cardiopulmonary bypass (CPB) for circulatory support,
and the need for intra-aortic balloon pump (IABP) circulatory support.

2.2.2. The postoperative (ICU) variables included


The serum troponin I level, the mean arterial blood pressure, the heart rate & rhythm, the ST-segment changes in the ECG,
the need for high inotropic support, the need for anti-arrhythmic drugs, the hours of postoperative mechanical ventilation,
the length of ICU stay and the incidence of in-hospital mortality.

2.3. Surgical management

Standard anesthetic and operative procedures were used as all the patients had conventional on-pump cardiac surgery in
both prosthetic valve replacement cases and CABG cases.
In the RIPC group and in the combined group the patient had repeated intermittent, transient, reversible, and non-lethal
upper limb ischemia by inflating a pressure cuff to 200 mmHg around the arm for 4 cycles of 5 min ischemia alternating with
5 min reperfusion starting from the time of induction of anesthesia.
In the hot shot group and in the combined group, the patient received 250 ml of warm perfusate (normothermic car-
dioplegia) at 37 C temperature infused to the aortic root via the antegrade cardioplegia cannula started 3e5 min prior to
aortic decalmping with a constant flow rate of 150 ml/min for 2 min.

Please cite this article in press as: Elgariah M, et al., Effect of terminal warm reperfusion (hot shot) and remote ischemic pre-
conditioning, either separately or combined, on myocardial recovery in adult cardiac surgery, Journal of the Egyptian Society of
Cardio-Thoracic Surgery (2017), http://dx.doi.org/10.1016/j.jescts.2017.07.005
M. Elgariah et al. / Journal of the Egyptian Society of Cardio-Thoracic Surgery xxx (2017) 1e6 3

The composition of the cold cardioplegia given to all groups was per liter of Ringer's solution: Sodium 97 mEq, Potassium
15 mEq, Chloride 92 mEq, Calcium 0.07 mEq, Bicarbonate 20 mEq, Glucose 25 g, Mannitol 12.5 g and Lidocaine HCl 120 mg.

Temperature of cardioplegia was 4 C and given initially at a dose of 20 ml/kg to be repeated every 25 min as 10 ml/kg.

2.4. Statistical analysis

The statistical analyses were performed using SPSS version 20 for Windows (SPSS, Chicago, IL). Continuous variables were
expressed as mean ± std, whereas categorical variables were expressed in terms of percentages and frequencies. For
continuous variables, analysis of variance (ANOVA) was used to compare means of different groups followed by post-hoc
tukey test. For comparing categorical variables, chi-square test was used. P values of <0.05 were considered statistically
significant.

3. Results

A total of 145 patients were divided into 4 groups, control group (group 1) 37 patients, hot shot group (group 2, 36 pa-
tients), RIPC patients group (group 3, 36 patients) and the combined group (group 4, 36 patients). The four groups were
matched in the demographic profile. Regarding preoperative variables including age, sex and patients' comorbidities, there
was no significant difference between 4 groups as shown in Table 1.
A significant difference was found between the 4 groups regarding the myocardial electrophysiological recovery, shown as
the time needed by the heart from declamping to restoration of effective myocardial electromechanical contraction (time to
regular mechanical activity) with the terminal hot shot group showed better protection than the control group.
Statistical significant difference was found in operative variables by comparing control group to the other 3 groups
including the rates of arrhythmias (heart block, atrial fibrillation, ventricular fibrillation),the rate of occurrence of ST-segment
ECG changes after aortic declamping, the need for a high inotropic support after aortic declamping, the need for antiar-
rhythmic drugs, the postoperative serum troponin level elevation, the need of IABP insertion, frequency of use of defibrillator,
time to regular mechanical activity, the heart rate after restoration of myocardial electromechanical activity, the mean arterial
blood pressure (ABP) after declamping and total CPB time as shown in Tables 2 and 3.
Regarding post-operative outcome variables, by comparing hot shot group, combined group and remote ischemic pre-
conditioning group to control group, we found that the rates of myocardial infarction, troponin I, inotropic support, the
occurrence of post-operative ST-segment changes, postoperative mean ABP, postoperative heart rate (HR) & rhythm, length of
postoperative ICU stay, the postoperative need for a high inotropic support in the ICU, and hospital deaths were statistically
significant as shown in Tables 4 and 5. Hot shot group had the best postoperative length of mechanical ventilation and ICU
stay and the best postoperative mean arterial blood pressure. We also found that hot shot group had the shorter aortic cross
clamp time, CPB time and reperfusion time.

4. Discussion

Our study was a single center prospective comparative study between the effect of infusion of terminal warm reperfusion
(hot shot) before removal of the aortic cross clamp, the effect of RIPC and the effect of both techniques together on myocardial
recovery in elective adult cardiac surgery.
In our study, comparison of myocardial protection with cold crystalloid cardioplegia without hot shot (the control group)
and the addition of terminal hot shot showed better recovery of myocardial electrophysiological activity in both CABG and
valve replacement in hot shot group and more patients spontaneously resumed sinus or the preoperative rhythm after the
operation.
In Teoh's et al. study [15], they compared cold blood cardioplegia to cold blood cardioplegia followed by a hot shot. They
found that there was preservation of energy stores, improvement of myocardial metabolic recovery, improvement in diastolic
function and washing out products of anaerobic metabolism in hot shot group.

Table 1
Pre-operative variables in different studied groups.

Control group (n ¼ 37) Hot shot Group (n ¼ 36) RIPC group (n ¼ 36) Combined group (n ¼ 36) P value
Age (mean ± std) 40.41 ± 12.85 43.69 ± 12.27 44.67 ± 9.62 45.39 ± 13.19 0.305
Sex
Female 68 16 (43.2) 17 (47.2) 19 (52.8) 16 (44.4) 0.853
Male 77 21 (56.8) 19 (52.8) 17 (47.2) 20 (55.6)
Incidence of pre-operative co-morbidity
HTN 2 (5.4) 1 (2.8) 3 (8.1) 1 (2.8) 0.648
DM 3 (8.1) 2 (5.6) 1 (2.8) 2 (5.6) 0.787
Obesity 1 (2.7) 1 (2.8) 3 (8.1) 1 (2.8) 0.555
TIA 2 (5.4) 2 (5.6) 2 (5.6) 3 (8.1) 0.949

(RIPC remote ischemic preconditioning; HTN hypertension; DM Diabetes mellitus; TIA Transient ischemic attacks).

Please cite this article in press as: Elgariah M, et al., Effect of terminal warm reperfusion (hot shot) and remote ischemic pre-
conditioning, either separately or combined, on myocardial recovery in adult cardiac surgery, Journal of the Egyptian Society of
Cardio-Thoracic Surgery (2017), http://dx.doi.org/10.1016/j.jescts.2017.07.005
4 M. Elgariah et al. / Journal of the Egyptian Society of Cardio-Thoracic Surgery xxx (2017) 1e6

Table 2
Intraoperative continuous variables in different studied groups.

Control group (n ¼ 37) Hot shot Group (n ¼ 36) RIPC group (n ¼ 36) Combined group (n ¼ 36) P value
Total CPB time(min)
(mean ± std) 161.05 ± 101.40 91.81 ± 22.41 102.75 ± 46.14 105.92 ± 67.00 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value < 0.001*) Combined vs control (p value 0.002*)
Aortic cross clamping time(min)
(mean ± std) 96.49 ± 44.95 63.42 ± 15.69 70.19 ± 28.23 73.25 ± 37.88 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value 0.005*) Combined vs control (p value 0.017*)
Reperfusion time(min)
(mean ± std) 22.05 ± 14.23 12.58 ± 4.43 14.81 ± 6.58 14.39 ± 7.14 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value 0.003*) Combined vs control (p value < 0.001*)
Time to regular mechanical activity (min)
(mean ± std) 17.35 ± 16.04 6.78 ± 3.35 8.14 ± 4.22 8.17 ± 10.92 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value < 0.001*) Combined vs control (p value < 0.001*)
Heart rate after restoration of myocardial electromechanical activity (beats/min)
(mean ± std) 110.68 ± 21.93 91.83 ± 11.84 98.56 ± 12.01 89.31 ± 19.09 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value 0.011*) Combined vs control (p value < 0.001*)
Mean ABP after declamping (mmHg)
(mean ± std) 58.78 ± 11.33 67.50 ± 7.42 66.39 ± 6.28 68.47 ± 8.52 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value < 0.001*) Combined vs control (p value < 0.001*)
Number of DC shocks needed after aortic declamping (frequency of use of defibrillator)
(mean ± std) 3.83 ± 1.70 2.06 ± 1.21 2.23 ± 0.82 2.25 ± 1.29 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value < 0.001*) Combined vs control (p value < 0.001*)

(RIPC remote ischemic preconditioning; CPB cardiopulmonary bypass, ABP arterial blood pressure).
* Significant (p value < 0.05).

Table 3
Intraoperative categorical variables in different studied groups.

Control group (n ¼ 37) Hot shot Group (n ¼ 36) RIPC group (n ¼ 36) Combined group (n ¼ 36) P value
Rhythm after aortic declamping
Sinus 115 24 (64.9) 32 (88.9) 27 (75) 32 (88.9) 0.028*
Arrhythmia 30 13 (35.1) 4 (11.1) 9 (25) 4 (11.1)
ST-segment changes in ECG after aortic declamping
No 129 28 (75.7) 35 (97.2) 33 (91.7) 33 (91.7) 0.021*
Yes 16 9 (24.3) 1 (2.8) 3 (8.3) 3 (8.3)
pH changes (metabolic acidosis) after aortic declamping
No 118 27 (73) 33 (91.7) 28 (77.8) 30 (83.3) 0.200
Yes 27 10 (27) 3 (8.3) 8 (22.2) 6 (16.7)
Need for high inotropic support after aortic declamping
No 124 26 (70.3) 34 (94.4) 31 (86.1) 33 (91.7) 0.016*
Yes 12 11 (29.7) 2 (5.6) 5 (13.9) 3 (8.3)
Intra-operative need for anti-arrhythmic drugs after aortic declamping
No 115 23 (62.2) 31 (86.1) 30 (83.3) 31 (86.1) 0.029*
Yes 30 14 (37.8) 5 (13.9) 6 (16.7) 5 (13.9)
Need for temporary cardiac pacing after aortic declamping
No 127 29 (78.4) 33 (91.7) 31 (86.1) 34 (94.4) 0.167
Yes 18 8 (21.6) 3 (8.3) 5 (13.9) 2 (5.6)
Need for IABP institution
No 136 30 (81.1) 35 (97.2) 36 (100) 35 (97.2) 0.003*
Yes 9 7 (18.9) 1 (2.8) 0 (0) 1 (2.8)

(RIPC remote ischemic preconditioning; IABP Intra-aortic balloon pump).


* Significant (p value < 0.05).

The clinical implications of our study results and findings go in the same direction as Teoh and colleagues' findings, who
found that a hot shot immediately prior to the release of the cross clamp resulted in better myocardial electromechanical
recovery. In Lubicz's study [16], using warm oxygenated cardioplegia supports the beneficial effects in terms of freedom from
ventricular fibrillation (VF), conduction defects, cardiac failure and myocardial infarction (MI). Cardiac function was resumed
after 15 min of warm reperfusion administration.
On the other hand, Edwards et al. [17] included a heterogeneous group of patients to see if there are systematic benefits
attributable to the “hot shot.” They have failed to show any difference in the postoperative release of the MB2 iso-form of
creatine kinase (CK), total CK-MB activity, or troponin-T between modified “hot shot” and unmodified reperfusion. Despite
being large study, it was the only study that failed to show the benefits of using hot shot protocol and this can be explained by
the different variables they have used. Crucially, the vast majority of randomized control trials investigating the effects of RIPC
are relatively small proof of concept studies and have often given discordant results for potential reasons.

Please cite this article in press as: Elgariah M, et al., Effect of terminal warm reperfusion (hot shot) and remote ischemic pre-
conditioning, either separately or combined, on myocardial recovery in adult cardiac surgery, Journal of the Egyptian Society of
Cardio-Thoracic Surgery (2017), http://dx.doi.org/10.1016/j.jescts.2017.07.005
M. Elgariah et al. / Journal of the Egyptian Society of Cardio-Thoracic Surgery xxx (2017) 1e6 5

Table 4
Post-operative continuous variables in different studied groups.

Control group (n ¼ 37) Hot shot Group (n ¼ 36) RIPC group (n ¼ 36) Combined group (n ¼ 36) P value
Postoperative mean ABP (mmHg)
(mean ± std) 58.24 ± 14.25 68.64 ± 6.41 66.28 ± 7.29 67.08 ± 13.49 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value 0.010*) Combined vs control (p value < 0.004*)
Postoperative heart rate (beats/min)
(mean ± std) 103.78 ± 26.88 90.78 ± 8.83 97.25 ± 12.49 87.23 ± 19.27 <0.001*
Hot shot vs control (p value 0.013*) RIPC vs control (p value 0.422) Combined vs control (p value < 0.001*)
Duration post-operative mechanical ventilation (hours)
(mean ± std) 10.24 ± 7.23 7.78 ± 4.18 9.33 ± 4.88 10.56 ± 15.61 0.574
Duration of postop ICU stay (days)
(mean ± std) 4.51 ± 2.52 3.64 ± 1.25 3.81 ± 1.26 3.36 ± 1.51 0.034*
Hot shot vs control (p value 0.133) RIPC vs control (p value 0.296) Combined vs control (p value 0.022*)
Total hospital stay (days)
(mean ± std) 14.3 ± 2.1 7.6 ± 1.8 10.2 ± 2.3 7.4 ± 1.5 <0.001*
Hot shot vs control (p value < 0.001*) RIPC vs control (p value < 0.001*) Combined vs control (p value < 0.001*)

(RIPC remote ischemic preconditioning; ABP Arterial blood pressure).


* Significant (p value < 0.05).

Table 5
Post-operative categorical variables in different studied groups.

Control group (n ¼ 37) Hot shot Group (n ¼ 36) RIPC group (n ¼ 36) Combined group (n ¼ 36) P value
Post-operative serum troponin level elevation
No 123 26 (70.3) 34 (94.4) 31 (86.1) 32 (88.9) 0.027*
Yes 22 11 (29.7) 2 (5.6) 5 (13.9) 4 (11.1)
Post-operative ST-segment changes in ECG
No 131 29 (78.4) 35 (97.2) 34 (94.4) 33 (91.7) 0.032*
Yes 14 8 (21.6) 1 (2.8) 2 (5.6) 3 (8.3)
Post-operative need for high inotropic support
No 116 23 (62.2) 32 (88.9) 31 (86.1) 30 (83.3) 0.017*
Yes 29 14 (37.8) 4 (11.1) 5 (13.9) 6 (16.7)
Post-operative need for antiarrhythmic drugs
No 101 22 (59.5) 29 (80.6) 23 (63.9) 27 (75) 0.180
Yes 44 15 (40.5) 7 (19.4) 13 (36.1) 9 (25)
Post-operative heart rhythm
Sinus 115 24 (64.9) 32 (88.9) 27 (75) 32 (88.9) 0.028*
Arrhythmia 30 13 (35.1) 4 (11.1) 9 (25) 4 (11.1)
Incidence of occurrence of post-operative complications (in the ICU)
Bleeding 2 (5.4) 2 (5.6) 2 (5.6) 1 (2.8) 0.930
Re-exploration 1 (2.7) 1 (2.8) 1 (2.8) 2 (5.6) 0.892
Heart block 3 (8.1) 2 (5.6) 3 (8.3) 3 (8.3) 0.961
Stroke 1 (2.7) 1 (2.8) 1 (2.8) 1 (2.8) 1.000
Hospital mortality
No 129 27 (73) 36 (100) 34 (94.4) 32 (88.9) 0.002*
Yes 16 10 (27) 0 (0) 2 (5.6) 4 (11.1)

(RIPC remote ischemic preconditioning).


* Significant (p value < 0.05).

In addition, a significant number of systemic reviews and meta-analyses in patients underwent cardiac surgery have been
conducted: the overall conclusion confirmed the beneficial effects of RIPC on peri-operative myocardial injury reduction,
however no statistically significant improvement of clinical outcomes was observed, including the mortality rate, periop-
erative MI, renal failure, stroke, mesenteric ischemia, hospital or ICU stay. The first study done by Li et al. [18] to describe the
impact of RIPC on patients’ morbidity and mortality in the context of cardiac surgery reported no post-operative death in
either preconditioned or control patients 30 days after elective aortic valve replacement, mitral valve surgery or double valve
replacement.
Similarly, no significant difference in major cardiac and cerebro-vascular events was found after one month post-
operatively in two other studies involving patients underwent CABG surgery with crystalloid cardioplegia [19,20]. Howev-
er, in our study we found that RIPC reduced the rate of death, MI, arrhythmia and the need for inotropic support.
Our study showed the myocardial protective effects of RIPC in patients underwent valve replacement surgery or CABG
surgery through decreasing the serum troponin level postoperatively, also reducing the inotropic support needed post-
operatively for these patients and improving the ventilation time and ICU stay time. This was similar to results given by Taha
et al. who confirmed the myocardial protective effect of remote ischemic preconditioning [21].
In terms of the inotropic support requirements, our study was consistent with Cheung et al., who found that there was a
significant reduction in inotropic support post-operatively [22].

Please cite this article in press as: Elgariah M, et al., Effect of terminal warm reperfusion (hot shot) and remote ischemic pre-
conditioning, either separately or combined, on myocardial recovery in adult cardiac surgery, Journal of the Egyptian Society of
Cardio-Thoracic Surgery (2017), http://dx.doi.org/10.1016/j.jescts.2017.07.005
6 M. Elgariah et al. / Journal of the Egyptian Society of Cardio-Thoracic Surgery xxx (2017) 1e6

Hong et al. [23] studied RIPC in 70 elective off-pump CABG patients via lower-limb ischemia (4 cycles of 5 min) and re-
ported that there was 50% reduction in cardiac enzymes postoperatively. In contrast to this study, Lucchinetti et al. [24]
concluded that no difference in cardiac enzymes postoperatively in patients subjected to RIPC.
Our study was in contrast to that of Thielmann et al. [20], who found that there was a non-significant decrease in inotropic
support requirement postoperatively. This may be because the mean age of the patients in our study was lower than that in
these studies and different types of operation of our study made the RIPC protocol more effective in decreasing the inotropic
requirement.
Our study was unique in evaluation of the combined group as the addition of both the hot shot and the RIPC together in the
same group of patients (the combined group) had not been done before.
The combined group had lower need for a high inotropic support after aortic declamping and this can be explained by the
earlier and better recovery of myocardial contractility and the lower incidence of ST-segment ischemic ECG changes after
aortic declamping (better myocardial protection). The postoperative elevation of serum troponin level was less in the
combined group than in the control group and this could be explained by the lower incidence of occurrence of both intra-
operative and post-operative ischemia with better myocardial protection.

5. Conclusions

From our study, we can conclude that terminal hot shot and remote ischemic preconditioning offer a powerful car-
dioprotective strategy for reducing and attenuating perioperative and peri-procedural myocardial injury in patients under-
going CABG surgery and prosthetic valve surgery.
The simplicity and non-invasive nature, as well as the flexibility of the timing of the remote ischemic conditioning
stimulus and the simplicity and availability of terminal hot shot make it feasible to apply in adult cardiac surgery.

References

[1] Ferrari R, Ceconi C, Curello S, Percoco G, Toselli TAG. Ischemic preconditioning, myocardial stunning, and hibernation: basic aspects. Am Hear J 1999;
138:61e8.
[2] Gundry SR. A comparison of retrograde cardioplegia versus antegrade cardioplegia in the presence of coronary artery obstruction. Ann Thorac Surg
1984;38(2):124e7.
[3] Buckberg GD. Update on current techniques of myocardial protection. Ann Thorac Surg 1995;60(3):805e14.
[4] Savunen T, Kuttila K, Rajalin A, Inberg M, Niinikoski J, Jalonen J, et al. Combined cardioplegia delivery offers no advantage over antegrade cardioplegia
administration in coronary surgical patients with a preserved left ventricular function. Eur J Cardiothorac Surg 1994;8(12):640e4.
[5] Allen BS, Winkelmann JW, Hanafy H, Hartz RS, Bolling KS, Ham J, et al. Retrograde cardioplegia does not adequately perfuse the right ventricle. J Thorac
Cardiovasc Surg 1995;109(6):1116e26.
[6] Winkelmann J, Aronson S, Young CJ, Fernandez A, Lee BK. Retrograde delivered cardioplegia is not distributed equally to the right ventricular free wall
and septum. J Cardiothorac Casc Anaesth 1995;9:135e9.
[7] Honkonen EL, Kaukinen L, Pehkonen EJ, Kaukinen S. Combined antegrade-retrograde blood cardioplegia does not protect right ventricular better than
either technique alone in patients with occluded right coronary artery. Scand Cardiovasc J 1997;31:289e95.
[8] Caputo M, Dihmis WC, Bryan AJ, Suleiman MS, Angelini GD. Warm blood hyperkalaemic reperfusion (’hot shot’) prevents myocardial substrate
derangement in patients undergoing coronary artery bypass surgery. Eur J Cardio-thorac Surg 1998;13(5):559e64.
[9] Kronon M. Delivery of a nonpotassium modified maintenance solution to enhance myocardial protection in stressed neonatal hearts: a new approach.
J Thorac Cardiovasc Surg 2002;123(1):119e29.
[10] Przyklenk K, Bauer B, Ovize M, Kloner RA, Whittaker P. Regional ischemic “preconditioning” protects remote virgin myocardium from subsequent
sustained coronary occlusion. Circulation 1993;87(3):893e9.
[11] Kanoria S, Jalan R, Seifalian AM, Williams R, Davidson BR. Protocols and mechanisms for remote ischemic preconditioning: a novel method for
reducing ischemia reperfusion injury. Transplantation 2007;84(4):445e58.
[12] Hausenloy DJ, Yellon DM. Preconditioning and postconditioning: new strategies for cardioprotection. Diabetes Obes Metab 2008;10(6):451e9.
[13] Tapuria N, Kumar Y, Habib MM, Amara MA, Seifalian AM, Davidson BR. Remote ischemic preconditioning: a novel protective method from ischemia
reperfusion injury-a review. J Surg Res 2008 Dec;150(2):304e30.
[14] Candilio L, Hausenloy DJ, Yellon DM. Remote ischemic conditioning: a clinical Trial's update. J Cardiovasc Pharmacol Ther 2011;16:304e12.
[15] Teoh KH, Christakis GT, Weisel RD, Fremes SE, Mickle DA, Romaschin AD, et al. Accelerated myocardial metabolic recovery with terminal warm blood
cardioplegia. J Thorac Cardiovasc Surg 1986;91(6):888e95.
[16] Lubicz SSM. Warm blood cardioplegia as an adjunct to myocardial preservation during coronary artery bypass grafting. Aust N. Z J 1991;61:127e32.
[17] Edwards R, Treasure T, Hossein-Nia M, Murday A, Kantidakis GH, Holt DW. A controlled trial of substrate-enhanced, warm reperfusion (’hot shot’)
versus simple reperfusion. Ann Thorac Surg 2000;69(2):551e5.
[18] Li S, Long C, Chang Q, Zhang D, Strickler AG, Nussmeier NA. Myocardial protection of warm blood cardioplegic induction during cardiopulmonary
bypass. J Extra Corpor Technol 2001;33(2):106e10.
[19] Thielmann M, Kottenberg E, Boengler K, Raffelsieper C, Neuhaeuser M, Peters J, et al. Remote ischemic preconditioning reduces myocardial injury after
coronary artery bypass surgery with crystalloid cardioplegic arrest. Basic Res Cardiol 2010;105(5):657e64.
[20] Thielmann M, Kottenberg E, Kleinbongard P, Wendt D, Gedik N, Pasa S, et al. Cardioprotective and prognostic effects of remote ischaemic pre-
conditioning in patients undergoing coronary artery bypass surgery: a single-centre randomised, double-blind, controlled trial. Lancet 2013;
382(9892):597e604.
[21] Taha AM, Elfeky WM, Ahmed MA, El-Heniedy MA. Nicorandil is as effective as limb ischemic preconditioning in reducing myocardial injury during
cardiac valvular surgery. J Egyt Soc Cardiothorac Surg; 2014;22(3):97e101.
[22] Cheung MM, Kharbanda RK, Konstantinov IE, Shimizu M, Frndova H, Li J, et al. Randomized controlled trial of the effects of remote ischemic pre-
conditioning on children undergoing cardiac surgery: first clinical application in humans. J Am Coll Cardiol 2006;47(11):2277e82.
[23] Hong DM, Jeon Y, Lee CS, Kim HJ, Lee JM, Bahk JH, et al. Effects of remote ischemic preconditioning with postconditioning in patients undergoing off-
pump coronary artery bypass surgeryerandomized controlled trial. Circ J 2012;76(4):884e90.
[24] Lucchinetti E, Bestmann L, Feng J, Freidank H, Clanachan AS, Finegan BA, et al. Remote ischemic preconditioning applied during isoflurane inhalation
provides no benefit to the myocardium of patients undergoing on-pump coronary artery bypass graft surgery: lack of synergy or evidence of
antagonism in cardioprotection? Anesthesiology 2012;116(2):296e310.

Please cite this article in press as: Elgariah M, et al., Effect of terminal warm reperfusion (hot shot) and remote ischemic pre-
conditioning, either separately or combined, on myocardial recovery in adult cardiac surgery, Journal of the Egyptian Society of
Cardio-Thoracic Surgery (2017), http://dx.doi.org/10.1016/j.jescts.2017.07.005

You might also like