摘要
Objective To investigate the myocardial protective effects of pinacidil induced hyperpolarized arrest and compare with those afforded by conventional depolarized hyperkalemic arrestMethods Eighteen dogs were equally divided into three groups: normothermic hyperpolarized group (Group A), hypothermic hyperpolarized group (Group B), and hyperkalemic group (Group C) Pinacidil (50μmol/L) containing 37℃ St Thomas solution (K+5mmol/L, 10ml/kg), pinacidil (50μmol/L, Sigma, USA) containing 4℃ St Thomas solution (K+ 5mmol/L, 10ml/kg) and 4℃ standard St Thomas solution (K+ 16mmol/L, 10ml/kg) were infused respectively through the aortic root after aorticclamping Heart arrest and its recovery, ultrastructure of the myocardium, the level of serum myocardial enzymes, and lipid peroxide and adenine cleotide of the myocardium were measuredHemodynamics during ischemia and after reperfusion were observedResults The percentages of normal mitochondria and glycogen did not change much during ischemia (except at 60 min) and after reperfusion in B Group, but declined markedly in Group C 30 min and 60 min after ischemia and 20 min after reperfusion (P<0.01) In Group A,they were lower than those of Group B before ischemia, but higher than those of Group C The recoveries of CO, SV, CI, LVSW, RVSW and MAP in Group B were significantly better than those in other two groups 15 min and 30 min after reperfusion (P<0.05and0.01, respectively) However, they were still better in Group A than those in Group C(P<0.05 and 0.01, respectively)The onset of heart arrest was faster in Groups C and B than that in Group A Highly elevated serum myocardial enzymes were observed 60 min after ischemia and 20 min after reperfusion in Group C, while they were only mild in the hyperpolarized groups, especially in Group B, and their recoveries were rapid Adenine nucleotides of the myocardium were better preserved in Group B than in other two groups 30 min, 60 min after ischemia, and 20 min after reperfusion (P<0.05 and 0.01, respectively)They were also much better in Group A than in GroupC(P<0.05and0.01,respectively)Lipid peroxide of the myocardium were significantly lower in Group B than in other groups 20 min after reperfusion (P<0.01),and they were lower in Group A than in Group C(P<0.05) Conclusions Myocardial protection for global ischemia during cardiopulmonary bypass (CPB) could be achieved with hyperpolarized heart arrest induced by pinacidil, an ATP sensitive potassium channel opener,especially in the hypothermic state The protection is weaker in normothermia but is still superior to that with traditional depolarized hyperkalemic arrest
目的 探讨Pinacidil诱导超极化停跳的心肌保护效果 ,并且与传统的高钾去极化停跳对比。方法 18只犬随机分为 3组 :常温超极化组 (A组 ) ,低温超极化组 (B组 )以及高钾组 (C组 )。主动脉根部分别灌注含Pinacidil (5 0 μmol/L)的 37℃St Thomas停跳液 (K+ 5mmol/L ,10ml/kgA组 ) ,同A组的 4℃停跳液 (B组 )或4℃标准St Thomas停跳液 (K+ 16mmol/L ,10ml/kg)。全心缺血 6 0min ,恢复循环 30min。对比观察并检测心脏缺血期间 ,以及恢复循环后心脏停跳及恢复情况、心肌超微结构、血清心肌酶含量、脂质过氧化物含量、心肌腺苷酸含量 ,以及血流动力学的变化。结果 (1)心肌组织超微结构 :阻断 30和 6 0min及再灌注 2 0min ,C组心肌正常线粒体及糖原含量均有下降 (P<0 0 1) ;B组仅缺血 6 0min时有显著性变化 ;而A组在缺血及再灌注期 ,正常线粒体及糖原含量均低于阻断前及B组 ,但显著高于C组。 (2 )血液动力学 :B组CO ,SV ,CI,LVSW ,RVSW ,MAP明显优于其它两组 (P <0 0 5或0 0 1) ,且A组也一定程度的优于C组。 (3)停跳情况 :B组、C组灌注后心脏停跳较A组迅速。 (4)血清心肌酶 :在缺血 6 0min ,以及开放循环 2 0min组 ,C组血清心肌酶含量显著增高 ,而在超极化组 ,尤其是B组仅轻微增高 ,恢复迅速。 (5 )
基金
theNationalNaturalScienceFoundationofChina (No .39760 0 71)
