雷诺嗪联合伊布利特对心房颤动兔的作用及其机制

Effect and its mechanism of ranolazine combined with ibutilide on rabbits with atrial fibrillation

目的研究雷诺嗪联合伊布利特抗心律失常作用及可能的离子机制。方法建立家兔急性心房颤动(AF)模型。按照体重将模型兔随机分为2组:联合组、伊布利特组,每组15只。联合组给予0. 1 mg·kg^(-1)伊布利特+2mg·kg^(-1)雷诺嗪静脉推注,伊布利特组仅给予0. 1 mg·kg^(-1)伊布利特静脉推注;随后2组均以11μg·kg^(-1)·min^(-1)速度静脉滴注维持。每组取12只,根据心电图观察并记录2组给药后的AF转复时间和转复成功率,以及转复过程中尖端扭转型心动过速(Tdp)的发生率。每组取3只,用全细胞膜片钳技术记录两组家兔心肌细胞给药前(0 min)及给药后30,60,120和240 min的快速激活延迟整流性钾电流(I_(Kr))变化状态与动作电位复极90%的间期(APD_(90))。结果联合组和伊布利特组的AF转复率分别为83. 33%和66. 67%;这2组的AF转复时间分别为(12. 13±3. 15),(20. 16±5. 42) min;这2组的Tdp发生率分别为0和8. 33%,2组间相比,上述指标的差异均有统计学意义(均P <0. 05)。结论雷诺嗪联合伊布利特可显著缩短AF转复时间,提高转复成功率,降低心房肌细胞兴奋性。

Objective To study the effect of ranolazine combined ibutilide on rabbit with atrial fibrillation(AF)and their possible ionic mechanism of antiarrhythmic.Methods The rabbits were used to establish an acute AF model.They were randomly divided into two groups:combination group(n=15)and ibutilide group(n=15).The combination group received an intravenous bolus of 0.1 mg·kg-1 ibutilide+2 mg·kg-1 ranolazine,and ibutilide group only gave an intravenous bolus of 0.1 mg·kg-1 ibutilide.Subsequently,both groups were maintained by intravenous infusion at a rate of 11μg·kg-1·min-1.Twelve in each group,according to the electrocardiogram,the AF conversion time and the success rate of conversion after the two groups of administration,and the incidence of torsades de pointes tachycardia(Tdp)during the conversion were recorded.Three in each group,the whole cell patch clamp technique was used to record the myocardial cells of the two groups before administration(0 min).The rapid activation delay rectifier potassium current(IKr)change state and the action potential repolarization 90%interval(APD90)at 30 min,60 min,120 min and 240 min after administration.Results The AF conversion rates in the combined group and the ibutilide group were 83.33%and 66.67%;the AF conversion time in the two groups were(12.13±3.15),(20.16±5.42)min;the incidence of Tdp in the two groups were 0 and 8.33%.Comparison between the combined group and the ibutilide group,the differences of the factors were significant(all P<0.05).Conclusion Ranolazine combined with ibutilide can significantly shorten AF conversion time,improve the success rate of transformation,and reduce the excitability of atrial myocytes.