Myocardial protective effect of pinacidil in immature rabbits

Objective The purpose of this study was to investigate the effect of pinacidil, an ATP-sensitive K + channel opener in protecting myocardium of immature rabbit heart from ischemia-reperfusion injury.Methods Fifty-two rabbits of 3-4 weeks old, weighing 350-450g were anesthetized with intraperitoneal pentobarbital sodium(50mg/kg). Hearts were excised and connected to modified Langendorff perfusion system and passively perfused with Krebs-Henseleit buffer(KHB) at 76 cmH 2O. Hearts were made globally ischemic for 30 min by aortic crossclamping and then reperfused for 30min. During ischemia the hearts received 20-25 ml cardioplegic solution of diferent constituents every 15 min. There were four groups with 13 hearts in each group based on the diferent constituents of cardioplegic solution: group Ⅰ(control, no cardioplegic solution); group Ⅱ(KHB+K + 16mmol/l); group Ⅲ(KHB+K +16mmol/L+pinacidil 50μmol/L); group Ⅳ (KHB+K +16mmol/L+glibenclamide 10μmol/L). Left ventricle developed pressure (LVDP), left ventricle diastolic pressure (LVEDP),±dp/dtmax, coronary flow (CF), and the levels of CK, LDH and AST in coronary sirnus veneous effluent and by myocardial ultrastructural changes. Myocardial ultrastructure was examined before and after ischemia.Results Before myocardial ischemia, there were no significant differences in the above mentioned parameters among four groups. Group Ⅲ was the best in terms of postischemic recovery of LVDP, LVEDP,±dp/dtmax and CF. The changes in CK,LDH,AST levels and myocardial ultrastructure were the least in group Ⅲ.Conclusions Pinacidil can afford best myocardial protection against ischemia-reperfusion injury in immature rabbit hearts.