增加缝隙连接耦联对兔长QT综合征心律失常的影响

Effect of enhancement of cardiac gap junction coupling on arrhythmia in rabbit LQTS model

目的:观察增加缝隙连接耦联对兔长QT综合征(LQTS)模型室性心律失常的影响。方法:应用心肌细胞快速延迟整流钾通道(IKr)阻滞剂E-4031(0.5μmol/L)在兔左室楔型心肌块建立LQT2模型,随机分为正常组、LQT2组、100 nmol/L缝隙连接激动剂(AAP-10)干预组(AAP-100组)、500 nmol/L AAP-10干预组(AAP-500组),每组10只。采用浮置玻璃微电极法同步记录心内膜、心外膜心肌细胞跨膜动作电位及跨室壁心电图。结果:LQT2组QT间期,跨室壁复极离散度(TDR)、早期后除极(EAD)、R-on-T期前收缩和尖端扭转性室性心动过速(TdP)发生率均显著高于正常组(P<0.05)。在LQT2模拟状态下,500 nmol/L AAP显著缩短了QT间期和TDR(P<0.05),降低了EAD、R-on-T期前收缩和TdP的发生率(P<0.05)。结论:增加缝隙连接耦联能减少兔LQT2模型TDR和室性心律失常发生率。

Objective：Gap junctions contribute to the transmural heterogeneity of repolarization in the normal heart and diseased heart. The present study was to evaluate the effects of antiarrhythmic peptide 10 （AAP10）, a kind of gap junctional activator, on ventricular arrhythmia in the rabbit ventricular model of LQT2. Method： An arterially-perfused rabbit left ventricular preparation and an IKr blocker, E-4031 （0.5 μmol/L）, were used to establish a model of LQT2. AAP10 was used to improve gap junction conductance. Preparations were randomly assigned to control, LQT2 and AAP10 groups. Transmural ECG as well as action potentials from both endocardium and epicardium were simultaneously recorded in the whole process in all experiments. Result：Compared with control group, the QT interval, TDR, EAD, R-on-T and TdP increased sharply in LQT2 group （P〈0.05）. In LQT2 models, presence of 500 nmol/L AAP10 reversed the effects of E-4031 to increase TDR and to induce TdP （P〈0. 05）. Conclusion：Enhancement of cardiac gap junction coupling reduces TDR and prevents ventricular arrhythmia in rabbit ventricular model of LQT2.