胺碘酮应用后再使用伊布利特的室性心动过速发生情况及机制探讨

The cardiac electrophysiological mechanism research for use of Ibutilide after the application of amiodarone

目的:研究胺碘酮与伊布利特联合应用对心肌室性心律失常的影响及机制.方法:新西兰大白兔35只,随机分配,分为A组:正常对照组、B组:含伊布利特质量浓度2 mg/L正常台式液灌流、C组:含伊布利特质量浓度2 mg/L低钾低镁台式液灌流、D组:含伊布利特质量浓度2 mg/L正常台式液灌流、E组:含伊布利特质量浓度2mg/L低钾低镁台式液灌流,每组7只.C组及D组实验前每日称量大白兔体质量,并根据体质量用电子天平称取质量分数50 mg/kg药粉,经灌胃针给予灌胃,每日1次,连续4周.实验时,每组大白兔均在麻醉后制作左室楔形心肌块,经左冠脉开口处灌流,记录内膜及外膜动作电位时程,计算出灌流前后跨壁复极离散(TDR)的改变,后给予程序刺激,观察室性心律失常发生情况.结果:单独使用伊布利特心肌TDR升高为(50.42±4.2)ms,较对照组的(41.7±15.3)ms明显升高(P<0.05).单独使用胺碘酮心肌TDR则降低为(16.8±3.3)ms,与对照组比较亦有显著差异.胺碘酮应用后再使用伊布利特心肌TDR改变为(27.22±5.1)ms,同样明显低于对照组TDR.而在低钾低镁环境下,单独使用伊布利特心肌TDR的升高则更为显著,达到(67.21±12.62)ms,而胺碘酮的降低心肌TDR的作用则与正常环境相同,为(16.8±3.3)ms.低钾低镁环境下胺碘酮应用后再使用伊布利特的心肌TDR为(32.21±5.2)ms,仍然明显低于对照组的心肌TDR水平.在观察室性心动过速的实验过程中,口服胺碘酮后再应用伊布利特,无论是在正常台式液环境还是低钾低镁台式液环境下,均无室速的发生,与在低钾低镁情况下单独使用伊布利特组中5只发生室速有明显差异(P<0.05).结论:口服胺碘酮后再使用伊布利特,可以减少依布利特单独使用时诱发的室性心律失常.

Aim：To study how the combined use of amiodarone with Ibutilide effects on myocardial transmural dispersion of repolarization （TDR）,and whether the combined use of Ibutilide with amioda-rone is able to reduce the side effects compared with the use of Ibutilide alone.Methods：35 New Zeal-and rabbits were randomly divided into control group,Ibutilide group A（perfused with normal tyrode＆#39;s so-lution containing 2 mg/L Ibutilide ）,Ibutilide group B （perfused with hypopotassemia and hypomag-nesemia tyrode＆#39;s solution containing 2 mg/L Ibutilide）,amiodarone （50 mg/kg amiodarone orally given every day for 4 weeks）combined with Ibutilide group A （perfused with normal tyrode＆#39;s solution contai-ning 2 mg/L Ibutilide）,amiodarone （50mg/kg amiodarone orally given every day for 4 weeks ）com-bined with Ibutilide group B（perfused with hypopotassemia and hypomagnesemia tyrode＆#39;s solution contai-ning 2 mg/L Ibutilide）,with 7 rabbits in each group.The left ventricular wedge preparations were made for each group.Transmural ECG and action potentials from both endocardium and epicardium were simul-taneously recorded.The changes of TDR and Tdp were analyzed.Results：In this study,TDR level was found to be increased to 50.42 ±4.2 ms in Ibutilide group A and 67.12 ±12.62 ms in Ibutilide group B, significantly higher than the control group.Amiodarone was found to be able to decrease TDR level to 16.8 ±3.3 ms in both amiodarone combined with Ibutilide group A and B.Based on the results,Ibutil-ide was used after the administration of amiodarone,and it was found that TDR level maintained at 27.22 ±5.1 ms in amiodarone combined with Ibutilide group A,and 32.21 ±5.2 ms in amiodarone combined with Ibutilide group B,significantly lower than that of the control group.In the arrhythmias experiment, we observed that arrhythmia occurred significantly less in amiodarone group B（0/7）than Ibutilide group B（5/7）.Conclusion：Amiodarone may be given orally for a period of time or up to 4 weeks before Ibutil-ide is given,which can effectively lower the risk of Tdp that might be caused by Ibutilide.This might im-prove the safety of Ibutilide.