钾通道开放剂心脏超极化停搏保护效果的研究

Hyperpolarized cardiac arrest with ATP-sensitive potassium channel opener on myocardial protection during CPB

目的 对比观察大剂量三磷酸腺苷 (ATP)敏感性钾通道开放剂吡那地尔对常温 /低温体外循环 (CPB)心脏超极化停跳缺血心肌的保护作用。 方法 18只犬随机分 3组 ,每组 6只。低温超极化组 (LH) :阻断升主动脉后 ,心脏灌注 4℃含吡那地尔停跳液 ,CPB血温为 2 6～ 2 8℃ ,开放前复温至 37℃。全心缺血 6 0min ,恢复灌注 30min ;常温超极化组 (WH) :CPB血温 35～ 37℃ ,心脏灌注37℃含吡那地尔 (5 0 μmol/L)停跳液 ,余同LH组 ;对照组 (C) :无吡那地尔的标准St.Thomas停跳液 ,余同LH组。对比观察吡那地尔心脏超极化停跳不同时相各项指标的变化。 结果 (1)停复跳情况 :LH组、C组灌注后心脏停跳较WH组迅速。开放后WH组心脏 4/ 6自动复跳 ,但收缩力较弱或发生室颤 ;LH组虽多去颤复跳 ,但收缩力较强 ;(2 )心肌组织超微结构 :阻断 30min后 ,C组、WH组心肌正常线粒体及糖原含量均有下降 (P <0 0 5 ,0 0 1) ,LH组仅阻断 6 0min时低于阻断前 (P <0 0 5 )。开放后WH组上述指标的恢复虽较C组迅速 ,但仍低于阻断前及LH组。 (3)血液动力学 :LH组血液动力学参数恢复较快 ,其中心输出量、每搏量、左室搏出功等项指标与C组、WH组比较差异有显著意义 ;而WH组优于C组。

Objective[WT5”BZ] To investigate the myocardial protective effects of pinacidil induced hyperpolarized arrest and compare them with those induced with depolarized hyperkalemic arrest. [WT5”HZ]Methods[WT5”BZ] 18 dogs were equally divided into three groups. In the hypothermic hyperpolarization group(LH group), after aortic cross clamping, a single dose of 4℃ pinacidil containing St. Thomas cardioplegic was infused through the aortic root. Temperature during CPB was kept between 26 28℃ and warmed to 37℃ before aortic declamping. Global ischemia lasted 60 min and then reconfusion started for 30 min. In the normothermic hyperpolarized group (WH group), the same procedure was set as in the LH group,except maintaining temperature of 35 37℃ for CPB and pinacidil solution. In the control group (group C), no pinacidil in St. Thomas solution was the only difference to the other 2 groups. Cardiac arrest and its recovery, the ultrastructure of the myocardium and hemodynamic during ischemia and after reperfusion were obsevred in the 3 groups. [WT5”HZ]Results[WT5”BZ] (1) The percentages of normal mitochrandria and glycogen were not changed significantly during ischemia and after reperfusion in the LH group, but declined markedly in the group C at ischemic 30, 60 min, and reperfusion for 20 min ( P <0 01). In the WH group, they were lower than those of the group LH, but higher than those of the group C before ischemia.(2) The recoveries of CO, SV, CI, LVSW, RVSW, MAP in the LH group were significantly better than those in the other two groups after reperfusion for 15 minutes and 30 minutes ( P <0 05 or 0 01). However, they were much better in the WH group than in the group C ( P <0 05 or 0 01). (3) The time from cardioplegic infusion to cardiac arrest was shorter in the group C and the group LH than in the group WH. [WT5”HZ]Conclusions[WT5”BZ] Myocardial protection for global ischemia during CPB could be well achieved with hyperpolarized cardiac arrest induced by ATP sensitive potassium channel opener, pinacidil,especially in the hypothermic state. The protection is weaker in normothermia but is still stronger than that with traditional depolarized arrest. [WT5”HZ]