The efficacies of modified mechanical post conditioning on myocardial protection for patients undergoing coronary artery bypass grafting

Serkan Durdu 0 1 Mustafa Sirlak 1 Demir Cetintas 1 Mustafa Bahadir Inan 1 Sadik Erylmaz 1 Evren Ozcinar 1 Levent Yazicioglu 1 Atilla Halil Elhan Ahmet Ruchan Akar 0 1 Adnan Uysalel 1 0 Stem Cell Institute, Ankara University , Ankara , Turkey 1 Department of Cardiovascular Surgery, Heart Center, Ankara University School of Medicine , Mamak Street, 06340, Dikimevi-Ankara , Turkey Background: Coronary artery bypass grafting (CABG) with cardioplegic cardiac arrest and cardiopulmonary bypass (CPB) is associated with myocardial injury. The aim of this study was to investigate whether a modified mechanical post-conditioning (MMPOC) technique has a myocardial protective effect by enhancing early metabolic recovery of the heart following revascularization. Methods: A prospective, randomized trial was conducted at a single-center university hospital performing adult cardiac surgery. Seventy-nine adult patients undergoing first-time elective isolated multivessel coronary artery bypass grafting were prospectively randomized to MMPOC or control group. Anesthetic, cardiopulmonary bypass, myocardial protection, and surgical techniques were standardized. The post reperfusion cardiac indices, inotrope use and biochemical-electrocardiographic evidence of myocardial injury were recorded. The incidence of postoperative complications was recorded prospectively. Results: Operative characteristics, including CPB and aortic cross-clamp time, were similar between the two groups (p>0.05). The MMPOC group had lower troponin I and other cardiac biomarkers level post CPB and postoperatively, with greater improvement in cardiac indices (p<0.001). MMPOC shortened post surgery hospitalization from 9.1 2.1 to 7.5 1.6 days (p<0.001). Conclusions: MMPOC technique promotes early metabolic recovery of the heart during elective CABG, leading to better myocardial protection and functional recovery. - Background Reperfusion has the potential to cause additional reversible and irreversible damage to the myocardium, which is called reperfusion injury [1,2]. The existence of postconditioning (POC) is the newest evidence that has emerged to support the concept of reperfusion injury. The term post conditioning refers to the phenomenon in which multiple brief periods of reperfusion interspersed with brief periods of ischemia (1060 s) result in a reduction in infarct size [3,4]. Generally, three cycles of ischemia/reperfusion are required to produce a maximal POC effect, although four and six cycles have been shown to be effective by some investigators [3,4]. However, it is the interval of reperfusion and ischemia that is the most critical factor in determining how efficacious POC will be. POC protocols shown to be maximally effective at reducing infarct size range from 10 to 60 s depending on the specific species being studied [3,4]. The aim of our study was to determine the efficacy of a modified type of mechanical post-conditioning (MMPOC) in patients undergoing elective coronary revascularization, with specific attention to biochemical markers of ischemic injury and post-surgical recovery of the patients and to show whether there is room for protection by post-conditioning amongst all the other cardioprotective factors. Methods Patients and protocol This study was approved by the Institutional Review Board of the University of Ankara and consisted of 79 patients undergoing elective primary coronary revascularization with 99% stenosis of the left anterior descending (LAD) artery. So as to include patients with relatively large volumes of at-risk myocardium, we limited our analysis to those patients exhibiting proximal occlusion of the LAD. Patients undergoing valve replacement, combined valve replacement/coronary revascularization, or preoperative coronary revascularization was excluded from the study. Informed consent was obtained from all patients before enrollment. Randomisation Patients were allocated to the MMPOC group or the study group using a computer-generated randomization code. Participants were randomly assigned in a 1:1 ratio. The study was open label and the primary investigator, who was not the treating physician and nurses informed the participants about their allocated treatment. Data for primary outcomes were assessed by use of a computer. Data collection and definitions Baseline, procedural, and follow-up data were stored prospectively in a database located at the University of Ankara. Patients preoperative risk factors were recorded and EuroSCOREs were calculated for each patient. Patients preoperative characteristics were recorded including age, sex, size, preexisting medical conditions, preoperative medications, preoperative ejection fractions. Intraoperative variables of which number of coronary bypass grafts, duration of cardiopulmonary bypass (CPB), duration of aortic cross-clamp, requirement for inotropic drugs, and/or intra-aortic balloon support, and blood product use were included. Postoperative data comprised myocardial infarction, cardiac tamponade, reoperation for occlusion or other causes, requirement of intra-aortic balloon pump support, neurologic complications, renal dysfunction, chest tube drainage during the first 24 postoperative hours, total chest tube drainage, the length of mechanical ventilator support, pneumonia, multiorgan failure, gastrointestinal complications, sepsis, coma, the length of intensive care unit (ICU) stay, and readmission within 90 days after surgery. Adverse events were defined as death, perioperative myocardial infarction, stroke, re-exploration due to bleeding, respiratory insufficiency, and renal failure. Perioperative myocardial infarction (MI) was defined as either new Q waves or ischemic ST segment changes with concomitant elevations of creatine kinase isoenzyme (CK-MB) > 5 times the upper limit of the reference range or a CK-MB to total creatine kinase (CK) ratio > 10% occurring within 48 hours after surgery or troponin I (TnI) > 1 ng/mL. Renal dysfunction was defined as rise of serum creatinine above 2.5 mg/dL and/or a need for hemodialysis. The surgical team examined all patients about 4-6 weeks after discharge and annually thereafter for two years. Anesthetic and surgical considerations Anesthesia was maintained with isoflurane. Hypertension was treated by increasing the concentration of isoflurane or by the administration of nitroglycerin if increasing the depth of anesthesia was ineffective. Hypotension was corrected using volume replacement or phenylephrine, as clinically indicated. An additional dose of 5 mg of midazolam was provided during rewarming from CPB. Inotropic agents (dobutamine 5 g/kg/min) were initiated for a cardiac indices (CI) <2.0 L/min/m2 after separation from CPB. At sternal closure, an infusion of propofol was started (25-75 g/ kg/min), and the isoflurane was discontinued. Propofol sedation was continued in the ICU until weaning of ventilatory support was initiated. All patients had coronary artery b (...truncated)