吡那地尔预处理对体外循环犬心肌的保护效果

The protective effects of pinacidil pretreatment on ischemic myocardium during cardiopulmonary bypass

目的 探讨ATP敏感性钾通道开放剂(KCOs)吡那地尔(Pinacidil)药物预处理对常温及低温犬体外循环(CPB)晶体高钾停搏液间断灌注心肌的保护效果。方法 18条犬随机分为三组,每组6条,分别建立犬的常温及低温CPB全心缺血Pinacidil预处理模型。对照组(A组):低温CPB,主动脉根部灌注4℃St.Thomas停搏液(K^+16mmol/L)10ml/kg,阻断30min复灌一次(1/2首量);B组:常温CPB,主动脉根部灌注37℃含氧Pinacidil液(0.083mg/kg);C组:低温CPB,主动脉根部灌注液同B组。三组心脏均接受60min缺血和30min再灌注。阻断主动脉前,开放后15min、30min测血液动力学改变;并循环5min,阻断循环30min、60min及开放循环20min于左心室取心肌组织,测定心肌腺苷酸含量。结果 再灌注期间C组的血液动力学指标明显好于A、B组(P<0.01),而B组又较A组好(P<0.01)。缺血及再灌注期间C组心肌的ATP含量也明显高于A、B组(P<0.01),B组又高于A组(P<0.01)。结论 Pinacidil预处理时对CPB下缺血心肌具有良好的保护效果,低温的效果优于常温。

Objective To evaluate the myocardial protective effect of pretreatment with pinacidil, a potassium channel opener, on myocardium perfused intermittently with normothermic or hypothermic high potassium crystalloid cardioplegie solution during cardiopulmonary bypass ( CPB) . Methods Eighteen dogs of both sexes weighing 10-15 kg were intubated and mechanically ventilated after induction of anesthesia. Femoral artery and vein were cannulated for direct MAP and CVP monitoring. Swan-ganz catheter was placed via right internal jugular vein. The animals were randomly divided into 3 groups: group A (hypothermic CPB) in which heart was perfused with 4℃ St Thomas solution 10 ml·kg-1 in 2 min and 30 min later perfused again with half of the initial volume(5 ml· kg-1); in group B (normotherinic CPB) and group C (hypothermic CPB) heart was pretreated with oxygenated pinacidil solution (0.083 mg·kg-1 37℃) before cardioplegia. The heart was subjected to 60 min global ischemia followed by 30 min reperfusion. The hemodynamic changes were measured before aortic cross-clamping and 15 and 30 min after release of aortic cross-clamping. Myocardial tissue was obtained from apex of left ventricle for determination of myocardial adenine nucleotide content 5 min after CPB was initiated, 30 and 60 min after aortic cross-clamping and 20 min after reperfusion. Results During reperfusion the hemodynamic function and myocardial ATP content recovered significantly better in group C than those in group A and B ( P < 0.01) and those in group B recovered significantly better than those in group A (P < 0.01) .Conclusion Pinacidil pretreatment has good protective effect on myocardium against ischemia especially under hypothermia.