LQT2模型尖端扭转型室性心动过速的发生机制

目的探讨LQT2模型早期后除极(EAD)、跨壁折返以及尖端扭转型室性心动过速(Tdp)的发生机制。方法采用冠状小动脉灌注兔左室心肌楔形组织块标本,应用浮置玻璃微电极动作电位及ECG同步记录技术,以IKr阻断剂d-sotalol作为工具药模拟LQT2,并与延迟整流钾电流IK阻滞剂azimilide对比,观察两者对兔心内膜和外膜层心肌细胞动作电位时程(APD)、跨壁复极离散度(TDR)、EAD、R-on-T早搏和Tdp的作用。结果d-sotalol和azimilide均显著延长心内膜和外膜层心肌细胞APD和QT间期;d-sotalol显著增加TDR,诱发EAD、R-on-T早搏和自发性Tdp的发生率分别为7/7,7/7和3/7;azimilide不增加TDR和不形成跨壁折返,但可诱发EAD和R-on-T早搏。结论通过冠状小动脉灌注兔左室心肌组织块LQT2模型,发现整体心室肌组织在QT延长的条件下,2相EAD是触发并引起Tdp的机制;TDR增加是产生EAD和形成折返的基础。

The mechanisms of torsade de pointes in LQT2 model

Objective To investigate the generation and transmural propagation of early afterdepolarization (EAD) , triggered activity and the initiating and maintaining mechanisms of torsade de pointes (Tdp). Methods An electrophysiological model in arterially perfused rabbit left ventricular wedge was made to simulate LQT2 model by using d-sotalol. The transmembrane action potentials of epicardium(Epi), endocardium(Endo) cells and transmural ECG in arterially perfused rabbit left ventricular wedge preparation were recorded by floating glass microelectrode.The role of d-sotalol and azimilide on action potential during(APD) of different layers,transmural dispersion of repolarization (TDR), EAD, and R-on-T premature beat and Tdp were observed . Results In arterially perfused rabbit left ventricular wedge preparation, d-sotalol and azimilide prolongated APD of Epi, Endo-cardiomyocytes and QT interval.D-sotalol increased TDR prominently, and the incidence of EAD,R-on-T premature beats and automatic Tdp were 7/7,7/7 and 3/7 respectively. Although azimilide could induce EAD and R-on-T premature beats too, it could not induce Tdp. Conclusions Phase 2 EAD can be generated and produce a trigger to initiate the onset of Tdp,and an increase of TDR can facilitate transmural propagation of EAD, reentry and the maintenance of Tdp.