匹那地尔对未成熟兔心肌的保护作用

Myocardial protective effect of pinacidil in immature rabbits

目的 探讨ATP钾离子通道开放剂匹那地尔对未成熟心肌常温缺血 /再灌注损伤的保护作用。方法 大耳白幼兔 (小于 2 8d) 5 2只随机分成 4组 :对照组 (Ⅰ组n =13) ,高钾停搏液组 (Ⅱ组n =13) :K H液中加氯化钾使钾浓度为 16mmol/L ;匹那地尔强化组 (Ⅲ组n =13) :高钾停搏液中加入匹那地尔 5 0 μmol/L ,格列苯脲拮抗组 (Ⅳ组n =13) :匹那地尔强化液加格列苯脲 10 μmol/L。在改良Langendorff模型上进行常温缺血 /再灌注离体心脏实验。观察缺血前后心功能变化 (左心室发展压、舒张末压 ,最大压力变化速率 ) ,冠状动脉流量 ,心肌酶值及超微结构改变。结果 匹那地尔强化组左心室功能 ,冠状动脉流量 ,心肌酶值及超微结构均优于其他三组。

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.