Introduction
============

Since the coronary artery bypass grafting (CABG) procedure was introduced, ischemia/reperfusion (I/R) injury has become one of the most challenging problems in modern cardiac surgery. Hence, numerous solutions and techniques have been introduced to preserve the myocardium during this type of surgery.[@b1-ARYA-11-186]-[@b4-ARYA-11-186]

Cold cardioplegia reduces the oxygen demands of myocardial cells by keeping the heart in an arrested state.[@b5-ARYA-11-186] As a consequence, the saved energy results in greater preservation of the heart and less reperfusion injury.[@b6-ARYA-11-186] Terminal warm blood cardioplegia (TWBC) has proved to be effective in reducing I/R injury.[@b5-ARYA-11-186]-[@b7-ARYA-11-186] The mechanisms which are responsible for myocardial protection using (TWBC) remain uncertain.[@b8-ARYA-11-186] In addition, TWBC has a significant impact in decreasing the incidence of I/R injuries, especially during coronary artery bypass surgery.[@b9-ARYA-11-186] There have been a number of studies conducted on patients undergoing coronary artery bypass graft using widely differing cardioplegia techniques, but there are fewer studies that have focused on hot shot administration during CABG and its clinical impact.[@b8-ARYA-11-186],[@b10-ARYA-11-186],[@b11-ARYA-11-186]

The aim of this study was to compare the effect of intermittent antegrade cold blood cardioplegia with or without TWBC (hot shot) on different clinical indictors in patients undergoing CABG.

Materials and Methods
=====================

A total of 2488 patients who underwent cardiac surgery in Sina Hospital, Isfahan, Iran, between 2003 and 2011, were enrolled in this study. Those patients who received warm blood cardioplegia or underwent reoperation were excluded. Patients were divided into two groups, those who only received intermittent cold blood cardioplegia (Group A, 925 patients) and those who were given intermittent cold blood cardioplegia, plus TWBC (hot shot) (Group B, 1563 patients). The research protocol was approved by the Ethics Committee of Isfahan University of Medical Sciences. All participants gave their written informed consent.

All of the surgeries were carried out by one surgeon, using the same surgical technique and devices. All of the patients were operated on with a median sternotomy. The left internal mammary artery (LIMA), saphenous vein, and radial artery were harvested simultaneously. Next, heparin 3 mg/kg was administered, and subsequently, cardiopulmonary bypass was established. The core body temperature was reduced to 34 °C (mild hypothermia). During the next stage, cardiac arrest was induced with antegrade cardioplegia through the ascending aorta via an inserted cannula. The radial artery was anastomosed to the arteries with more than 90% stenosis, in order to prevent competitive flow, which can compromise graft flow through the radial artery. Next, a saphenous vein graft was applied to the arteries based on angiographic findings. Then, the LIMA was anastomosed to the left anterior descending artery. After each distal anastomosis, 200-300 cc antegrade warm blood cardioplegia (hot shot) was administered randomly.

All of the patients received intermittent cold cardioplegia (1:8).

Data were gathered from Sina's Hospital electronic database, which is based on European Association of Cardiothoracic Surgeons' database. The technique of the surgeries and devices, which were used during cardiac surgery to all of the patients were the same. All statistics were carried out by SPSS software for Windows (version 16.0, SPSS Inc., Chicago, IL, USA). Data were shown as frequency (%) (or mean ± standard deviation where appropriate). For comparing qualitative variables between groups chi-square test (or Fisher exact test where appropriate) and for comparing quantitative variables independent sample t-test used. Multiple logistic regressions were used to determine multiple effects. P \< 0.050 considered to be statistically significant. Variables included: sex, intra-aortic balloon pump post-operative, arrhythmia of premature atrial contraction (PAC), diabetes treatment, and hospital stay. Ejection fraction (EF) category defined as good (\> 50%), fair (30-50%) and poor (\< 30%).[@b12-ARYA-11-186] The arrhythmias that recorded in this study are after weaning of cardiopulmonary bypass.

Results
=======

In this study, a total of 2488 patients were selected (693 males and 1795 females). Mean length of the patients' hospital stay for those who received direct current (DC) shock was 7.81 ± 3.20 and for those who did not (7.92 ± 4.77). Overall, 1.1% had PAC arrhythmia. In total, 62.8% of the patients received antegrade hot shot). [Table 1](#t1-ARYA-11-186){ref-type="table"} shows the demographic characteristics of subjects who received an antegrade hot shot in compared with no DC shock.

There were significant differences between receiving DC shock based on hot shot with regard to: sex, EF category, diabetes treatment (P \< 0.050). The non-diabetic patients who received hot shot got less DC shock (P = 0.019). In Group B, female subjects and diabetic patients with oral agents got less DC shock. Subjects with good EF level received less DC shock in Group B (P = 0.003) ([Table 1](#t1-ARYA-11-186){ref-type="table"}). [Table 2](#t2-ARYA-11-186){ref-type="table"} shows the effect of antegrade hotshot on dc shock within group of peri and post-CABG complications. In Group B, those who experienced PAC and atrial fibrillation the need for DC shock cardioversion were less. Multiple logistic regression showed that receiving a hot shot in subjects who had PAC arrhythmia had no significant effect on DC shock during CAGB \[0.84 (0.25-2.85) P = 0.780\]. Prevalence of other arrhythmias was few in cases. Multiple logistic regression showed that having poor EF level increased the risk of receiving DC shock among subjects by 2.81 (1.69, 4.69) (P \< 0.001) ([Table 3](#t3-ARYA-11-186){ref-type="table"}). In this regard, using antegrade hotshot decreased the chance of getting DC shock by 0.65 (0.51, 0.84) (P = 0.001). Among the diabetic subjects, receiving insulin decreased the risk of DC shock by 0.54 (0.29, 0.98) (P = 0.042). In Group B the mean length of hospital stay in those who received DC shock was not statistically significant (0.775).

Discussion
==========

Our results showed that a single antegrade hot shot following cold cardioplegia is not significantly effective in the CABG group. TWBC will decrease the chance of receiving Dc shock by 0.35 \[0.65 (0.51, 0.84), P = 0.001\]. Good EF (\> 50%) shows that the heart muscle is strong. Obviously those patients with good EF required less DC shock. Undoubtedly those with pre-operative sinus rhythm will need less DC shock. Diabetic subjects who controlled their diabetes mellitus (DM) with oral agents received 0.69 times more TWBC, however, in patients using other methods this was not the case. Diabetic patients who controlled their blood glucose with oral drugs alone, required less defibrillator during their surgery, this may be because of the lower levels of free radicals and better control of DM in these patients. Single hot shot does not seem to have an effect on the different types of arrhythmia. The length of hospital stay and spontaneous rhythm time from declamping were not statistically significant. As discussed above, the effect of single antegrade hot shot on defibrillator usage during cardiac surgery is still a matter of debate. In our literature review, the studies that examined the positive effects of hot shot in reducing DC shock defibrillator were rare. In contrast to our findings, Goncu et al. showed that antegrade hot shot does not affect DC shock usage. They concluded that combined antegrade cardioplegic infusion via the aortic root, with additional cardioplegia from a vein or free arterial grafts after each distal anastomosis, will result in decreased DC shock usage.[@b13-ARYA-11-186] Contrary to our findings, Ghazy et al. showed that single shot cardioplegia does not change the incidence of arrhythmia.[@b3-ARYA-11-186] Moreover, Akowuah et al. showed that retrograde cardioplegia does not have an effect on ventricular tachycardia/ventricular fibrillation arrhythmia during surgery.[@b8-ARYA-11-186] In addition, Falcoz et al. reported there was no difference in the number of electroshocks administered between two groups of cold crystalloid cardioplegia, followed by warm and cold crystalloid cardioplegia. Falcoz et al. compared electroshock usage only in heart valve surgery, and the sample size was 70 patients. The content of the cardioplegia solution was also different from ours.[@b14-ARYA-11-186] It is concluded that single antegrade hot shot can have an effect on DC shock usage during cardiac surgery. It can lower defibrillator usage 1.55-fold in contrast to not administering hot shot.

It is assumed that the constituents of the hot shot are also effective in preserving myocardial function because of the lower damage, but more biochemical studies are required in order to evaluate the exact effect of this solution. The limitation of our study is that we did not evaluate the biomarkers in the two groups of patients, and the post-operative parameters are few in number. More studies favorably randomized clinical trials are needed in future in order to find the best contents for a hot shot and cold cardioplegia.

Assurances

-   · The research protocol was approved by the Ethics Committee of Isfahan University of Medical Sciences. All participants gave their written informed consent

-   · The source of funding for the study: N/A

-   · Financial disclosure: N/A.

My warmest gratitude goes to Ms. Rahnama, Head of the Informatics' Unit of Sina Hospital, for her kindly cooperation.

**Conflicts of Interest**

Authors have no conflict of interests.

###### 

Effect of antegrade hot shot on direct current (DC) shock within group of different demographic characteristics

  Characteristics   Ante grade hot shot   DC-shock     P
  ----------------- --------------------- ------------ -------
  Sex                                                  
   Male             Yes                   32 (9.1)     0.491
  No                27 (10.8)                          
   Female           Yes                   128 (11)     0.001
  No                104 (16.4)                         
  EF category                                          
   Poor             Yes                   15 (22.4)    0.460
  No                8 (29.6)                           
   Fair             Yes                   79 (11.6)    0.198
  No                58 (14.3)                          
   Good             Yes                   69 (8.5)     0.003
  No                67 (13.6)                          
  Diabetes treat                                       
   Oral alone       Yes                   29 (7.5)     0.048
  No                28 (12.3)                          
   Diet             Yes                   10 (16.7)    0.717
  No                5 (13.9)                           
   Insulin          Yes                   9 (7.1)      0.975
  No                4 (7.3)                            
   None             Yes                   116 (11.7)   0.019
  No                96 (15.9)                          

EF: Ejection fraction; DC: Direct current

###### 

Effect of antegrade hot shot on direct current (DC) shock within group of peri and post coronary artery bypass grafting (CABG) complications

  Arrhythmia       Ante grade hot shot   DC-shock    P
  ---------------- --------------------- ----------- ----------
  PAC arrhythmia                                     
   No              Have                  55 (10.0)   0.002
  Not have         150 (15.6)                        
   Yes             Have                  1 (25.0)    \> 0.999
  Not have         3 (17.6)                          
  AF arrhythmia                                      
   No              Have                  52 (10.3)   0.009
  Not have         131 (15.2)                        
   Yes             Have                  4 (8.7)     0.117
  Not have         22(18.6)                          

DC: Direct current; PAC: Paroxysmal atrial contracture; AF: Atrial fibrillation

###### 

Multiple logistic regressions for effect of characteristics on no need to direct current (DC) shock

  Characteristics        OR (95.0% CI)       P
  ---------------------- ------------------- ----------
  Sex (female)           1.21 (0.89, 1.66)   0.226
  PAC arrhythmia (yes)   0.84 (0.25, 2.85)   0.780
  EF category                                
   Poor                  2.81 (1.69, 4.69)   \< 0.001
   Fair                  1.22 (0.94, 1.58)   0.136
   Good (ref)            1                   \-
  Diabetes treat                             
   Oral alone            0.69 (0.51, 0.96)   0.026
   Diet                  1.24 (0.69, 2.21)   0.465
   Insulin               0.54 (0.29, 0.98)   0.042
   None (ref)            1                   \-
   Hospital stay         1.21 (0.89, 1.66)   0.226
   Ante grade hot shot   0.65 (0.51, 0.84)   0.001

Values are multiple adjusted by each other; PAC: Paroxysmal atrial contracture; OR: Odd ratio; CI: Confidence interval; EF: Ejection fraction
