Role Of Opioid Receptor In Cardioprotection After Ischemia-Reperfusion During Cardiopulmonary Bypass

Objective: By establishing the swine cardiopulmonary bypass(CPB) myocardial ischemia-reperfusion (MI/R) model,the early phase and the late phase cardioprotective effects were studied by using theδ-opioid receptor agonist [D-Ala², D-Leu⁵] Enkephalin(DADLE) and the mitochondrial K_ATP channel antiagonist Glibenclamide to provide academic and experimental evidences for clinical cardioprotection.Methods: 32 adult swines(30-35kg) were randomly divided into 4 groups: group C, group D1, group D2 and group D＋K(n=8). CPB was instituted routinely and the improved St. Thomas cold cardioplegic solution was administered into the root of aorta. Blood samples were taken from coronary sinus before CPB, beginning of reperfusion, the end of CPB, one hour after CPB, two hours after CPB to measure TnT. The LVSP, LVEDP and±dp/±dtmax were measured at the corresponding time points. Specimens of the left ventricular myocardium were taken before CPB and two hours after CPB for the expressions of Gia protein and PKC, the values of ATP. And the cardium ultrastructures were observed.Results: (1)Parameters of cardiac function in group D1 and D2 were found obviously better than those in group C and D＋K, and group D2 could improve the diastolic cardiac function better than group D1. (2)Concentrations of TnT increased obviously in group C and D＋K compared with group D1. And there was no statistical significance of the Concentrations of TnT in group D2 all through the experiment. (3)The values of ATP in Group D1 and D2 were obviously higher than those in group C and D＋K. There was no statistical significance of the values of ATP between group D2 and nonpreconditioned myocardium, but the values of ATP in group D1 were lower than those in group D2 and nonpreconditioned myocardium. (4)Group D1 and D2 showed slight injuries in electron microscopy than those in group C and D＋K, and group D2 had more advantages than group D1. (5)The expressions of Gia protein and PKC in group D1 and D2 were obviously higher than those in group C, group D＋K and nonpreconditioned myocardium.Conclusions: (1)Compared with the early phase cardioprotection induced by-opioid receptor agonist DADLE after CPB in swine, the late phase cardioprotection has more advantages. (2)The early phase cardioprotection can be blocked with the mitochondrial K_ATP channel antiagonist Glibenclamide. (3) Gi-PKC-Mitochondrial K_ATP Channel is an important signaling pathway in theδ-opioid receptor-induced cardioprotection.