长QT综合征复极化离散与早期后除极致心律失常机制的跨壁光学标测研究

Optical mapping of the transmural dispersion of repolarization and early after depolarization in LQT2 and LQT3 models of long QT syndrome

目的 尖端扭转性室性心动过速 (室速 )是长QT综合征 (LQTS)的致命性心律失常 ,相关机制的细胞学水平研究还不十分清楚。本文报道对复极化离散和触发机制在尖端扭转性室速发生中的作用的研究结果。方法 动脉灌注的犬左心室楔形心肌块 ,经电压敏感性荧光染色后 ,行跨壁包括百余位点跨膜动作电位的同步光学标测研究。d 索他洛尔、海银花 (ATX Ⅱ)分别用来模拟LQT2和LQT3。对照组、LQT2组、LQT3组各 6块。结果 正常对照组的平均动作电位时限 (APD)为 (2 91± 2 7)ms,跨壁复极化的离散(DOR)为 (2 4± 6 )ms;LQT2组APD为 (35 6± 2 0 )ms,DOR为 (35± 9)ms,与对照组相比差异有显著性 (P <0 0 5 ) ;LQT3组APD为 (6 0 9± 92 )ms,DOR为 (12 1± 85 )ms,与对照组相比差异有显著性 (P <0 0 5 )。在LQT3组 ,早期后除极现象可见于所有类型的心肌细胞 ,但以心内膜和中层心肌细胞多见。触发活动常常起源于中层心肌细胞部位。结论 在LQT条件下 ,跨壁动作电位不均一地延长是导致复极化离散的重要原因 ,为心律失常的发生提供了基质。

Objectives Torsade de pointes (TdP) is a life-threaten arrhythmia and the cellular mechanism of it is still questioned.The aim of this study is to investigate the arrhythmiasgenesis of transmural dispersion of repolarization (DOR) and triggered activity in LQT syndrome.Methods Optical mapping was used to measure transmural action potentials duration (APD) from the arterially perfused left ventricular canine wedge preparation.D-sotalol and ATX-Ⅱ were used to mimic LQT2 and LQT3,respectively.Each group included 6 preparations.Results The mean APD were(291±27)ms, (356±20) ms,(609±92) ms in control,LQT2,and LQT3 condition,respectively,(P<0.05).The DOR were (24±6) ms,(35±9) ms,(121±85) ms in control,LQT2,and LQT3 group,(P<0.05).All three kinds of myocardial cells had the potential to generate early afterdepolarization (EADs) .But it more likely occurred in endomyocardial cells and M cells.EAD-induced triggered activity often originated from M cells.Conclusions Inhomogeneous transmural action potential prolongation plays an important role in repolarization dispersion and provides the substrate for arrhythmiasgenesis.EADs and EAD-induced triggered activity are enhanced under conditions of prolonged APD and have also been shown to play an important role in the initiation of TdP.