Role of mitochondrial KATP channel in opioid cardioprotection after Ischemia-reperfusion during cardiopulmonary bypass

Abstract

Objective By establishing the swine cardiopulmonary bypass(CPB) myocardial ischemia-reperfusion (MI/R) mod-el, the early phase cardioprotective effects and the role of the mitochondrial KATP channel were studied to provide basic and experimen-tal evidences for clinical card-ioprotection. Methods 24 adult swines(30-35 kg) were randomly divided into 3 groups:group C(con-trol group, n=8), group D(using δ-opiold agonist-DADLE,n = 8) and group D+ K (using DADLE and Glibenclamide, n=8).CPB was instituted routinely and the improved St. Tboreas cold cardioplegic solution was administered into the root of aorta. Blood sam-plea were taken from coronary sinus before CPB,beginning of reperfusion, the end of CPB, one hour after CPB,two hours after CPB tomeasure TnT. The LVSP, LVEDP and ± dp/dtmax were measured at the corresponding time points. Specimens of the left ventricularmyocardium were taken before CPB and two hours after CPB for the expressions of Gia protein and PKC,the values d ATP. And thecardium ultrastructures were observed. Results ( 1 )Parameters of cardiac function in group D were found abviously better than those ingroup C and D + K. (2)Concentrations of TnT increased obviously in group C and D+K compared with group D. (3)The values of ATPin Group D were obviously higher than those in group C and D + K. (4)Group D showed slight injuries in electron microscopy than thosein group C and D + K. (5)The expressions of Gia protein and PKC in group D were obviously higher than those in group C,group D+K and nonpreconditioned myocardium. Conclusion (1)δ-opioid receptor agonist DADLE could induce the early phase cardioprotectionafter CPB in swine. (2)Gi-PKC-Mitochondrial KATP Channel is an important signaling pathway in the early phase cardioprotection. Key words: Myocardial reperfusion injury Receptor,opioid Cardiopulmonary Bypass Mitochondrial KATP channel