【摘要】 目的本研究通过制作一种模拟LQT2的动物模型——Langendorff离体灌流兔心脏LQT2的动物模型,然后用钾通道开放剂吡那地尔(pinacidil)干预,研究吡那地尔对离体LQT2兔心脏模型心室复极的影响,并探讨其作用机制。方法将30只体重为2.5～3.5kg的健康新西兰兔随机分为A、B、C三组,A组(对照组),B组(吡那地尔组),C组(吡那地尔+优降糖组)。取出心脏,立即行逆行主动脉灌注,然后用有齿镊钳夹房室结造成Ⅲ度房室传导阻滞,在Langendorff离体灌流兔心脏上同步记录左室心内膜及心外膜单相动作电位和容积传导心电图。分别用1000ms刺激周长(CLs)起搏至少100个心动周期,体表心电图提示无ST-T明显压低或抬高。然后用加有右旋索他洛尔(d-Sotalol)100μmol/L浓度的台氏液逆行Langendorff灌流30min后再分别用上述刺激周期进行刺激,观察:①90%动作电位时程(APD90);②90%复极时间(RT90);③跨室壁复极离散度(TDR);④早期后去极化(EAD)及尖端扭转型室性心动过速的发生率;⑤平均QT间期等的变化。并对A、B、C三组进行不同的药物制剂干预。结果右旋索他洛尔明显延长离体兔心脏心内膜及心外膜单相动作电位时程(P<0.001);TDR延长(P<0.001);同步记录容积传导心电图的QT间期延长(P<0.001);EAD发生率从0%到86.67%(P<0.01);TdP发生率从0%～43.33%(P<0.05)。吡那地尔缩短由d-Sotalol所引起的动作电位时程延长,使左室心内膜、心外膜的APD90缩短,缩短容积传导心电图QT间期,减少跨壁复极离散度TDR(P<0.001);消除早期后去极化EAD(P<0.01),并抑制触发性心律失常TdP(P<0.05)。吡那地尔+优降糖组的结果显示:APD90、TDR、EAD、TdP等指标在处理后与对照组相比,P>0.05,无统计学意义。结论吡那地尔能抑制LQT2兔心律失常的发生。更多还原

【Abstract】 Objective To study the effects of Pinacidil on Ventricular Repolarization in LQT2 Rabbit Heart.Methods 30 New Zealand white rabbits weighted from 2.5~3.0 kg were randomly divided into 3 groups:group A(control),group B(pinacidil),group C(pinacidil + glibenclamide).Left ventricular endocardium and epicardium MAPs and volume-conducted ECGs in isolated Langendorff-perfused rabbit hearts were recorded simultaneously.To induce bradycardia,the AV nodes of rabbit hearts were damaged.EAD and TdP were induced by means of bradycardia in the presence of high concentration of d-sotalol(10-4M).Results In group B,pinacidil(5μmol/L)shortened the APD90 on endocardium from 445.48±54.31ms to 278.87±44.45ms after administration of pinacidil for 5 minutes(P<0.001,vs.group A)and to 256.86±38.44ms for 10 minutes(P<0.001,vs.group A),respectively;whereas on epicardium,the APD90 decreased from 340.45±37.87ms to 230.32±40.11ms after administration of pinacidil for 5 minutes(P<0.001,vs.group A)and to 214.89±37.87ms for 10 minutes(P<0.001,vs.group A).TDR decreased from 144.35±28.43ms to 46.34±11.23ms after administration of pinacidil for 5 minutes(P<0.001,vs.group A)and to 41.37±12.65ms for 10 minutes(P<0.001,vs.group A),respectively.The incidence of EADs decreased from 90% to 20% and to 10%(both P<0.01,vs.group A),and the incidence of TdP decreased from 50% to 10% for both time points(P<0.05,vs.group A).Whereas in group C,there was no effects of pinacidil + glibenclamide on APD90,TDR and the incidence of EADs and TdP(P>0.05 vs.group A for all).Conclusion Pinacidil can decrease prolonged action potencial duration and TDR induced by bradycardia and high concentration of d-sotalol in rabbit hearts.Also,pinacidil could abolish the EAD and TdP related to delayed repolarization that may provide a novel and useful intervention in the clinical LQTS patients.更多还原