Abstract
Identification of microRNAs (miRNA) associated with cardiopulmonary bypass, cardiac arrest and subsequent myocardial ischemia/reperfusion may unravel novel therapeutic targets and biomarkers. The primary aim of the present study was to investigate the effects of cardiopulmonary bypass and temperature of cardioplegic arrest on myocardial miRNA profile in pigs’ left ventricular tissue. We employed next-generation sequencing to analyse miRNA profiles in the following groups: (1) hearts were arrested with antegrade warm St Thomas Hospital No. 2 (STH2) cardioplegia (n = 5; STH2-warm, 37 °C) and (2) cold STH2 (n = 6; STH2-cold, 4 °C) cardioplegia. Sixty min of ischemia was followed by 60 min of on-pump reperfusion with an additional 90 min of off-pump reperfusion. In addition, two groups without cardiac arrest (off-pump and on-pump group; n = 3, respectively) served as additional controls. STH2-warm and STH2-cold cardioplegia revealed no hemodynamic differences. In contrast, coronary venous creatine kinase-myocardial band (CK-MB) levels were significantly lower in pigs receiving STH2-warm cardioplegia (p < 0.05). Principal component analysis revealed that cardiopulmonary bypass and cardioplegic arrest markedly affected miRNAs in left ventricular tissue. Accordingly, ssc-miR-122, ssc-miR-10a-5p, ssc-miR-193a-3p, ssc-miR-499-3p, ssc-miR-374a-5p, ssc-miR-345-5p, ssc-miR-142-3p, ssc-miR-424-5p, ssc-miR-545-3p, ssc-miR-30b-5p, ssc-miR-145-5p, ssc-miR-374b-5p and ssc-miR-139-3p were differently regulated by cardiopulmonary bypass (false discovery rate (FDR) < 0.05 versus off-pump group). However, only ssc-miR-451 was differently expressed between STH2-warm and STH2-cold (FDR < 0.05). These data demonstrate for the first time that cardiopulmonary bypass and temperature of cardioplegic solution affected the expression of miRNAs in left ventricular tissue. In conclusion, specific miRNAs are potential therapeutic targets for limiting ischemia-reperfusion injury in patients undergoing cardiac surgery.
Highlights
In cardiac surgery, the number of elderly and multimorbid patients has dramatically increased over the last 20 years, which overall results in increased peri- and post-operative mortality [1,2].constant efforts are needed to enhance intraoperative myocardial protection and, subsequently, improve postoperative outcomes
Seventeen pigs were included in the study (STH2-warm: n = 5, body weight (BW) 64 ± 5 kg, heart weight (HW) 322 ± 19 g, ejection fraction (EF) 58% ± 8%
Cardiac surgery, cardiopulmonary bypass (CPB) andthe cardioplegic arrest are key triggers of myocardial during cardiac. This is because heart is exposed to global ischemia myocardial injury during cardiac surgery
Summary
The number of elderly and multimorbid patients has dramatically increased over the last 20 years, which overall results in increased peri- and post-operative mortality [1,2]. Constant efforts are needed to enhance intraoperative myocardial protection and, subsequently, improve postoperative outcomes. Ischemia and the subsequent reperfusion injury (IR) are triggered by marked calcium overload and oxidative stress of cardiomyocytes, causing myocardial apoptosis and inflammation. Cardiac arrest is routinely induced by cardioplegic solutions to allow coronary artery bypass surgery (CABG), cardiac transplantation and aortic valve procedures. Myocardial protection is ideally achieved by using warm or cold cardioplegic solution. The debate about the right application temperature is still ongoing.
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