短QT间期发生室性心律失常的电生理机制探讨

目的了解短QT间期发生室性心律失常的电生理机制。方法应用吡那地尔在家兔左室楔形灌注组织建立短QT模型,利用标准玻璃微电极技术记录心外膜下、心内膜下及中层心肌细胞动作电位,并观测三层心肌细胞复极达90%的动作电位(APD90)及跨壁复极离散度(TDR)在吡那地尔、吡那地尔+异丙肾上腺素、奎尼丁、glybenclamide作用下的变化。采用S1S2程序刺激,观测在各种条件下心律失常的诱发状况。结果吡那地尔明显缩短APD90且伴有TDR增大(58.84±13.42ms vs35.26±13.30ms),并可诱发出异常心肌搏动。异丙肾上腺素可增大吡那地尔的该作用(64.60±21.46ms vs58.84±13.42ms),而奎尼丁和glybenclamide则可逆转吡那地尔的此作用,并减少异常搏动的发生。结论TDR增大可能是短QT综合征易于发生致命性心律失常的基础,而奎尼丁通过减小室壁心肌细胞的不均一性而对短QT综合征起到治疗作用。

Study of electrophysiological mechanism of ventricular arrhythmias in the short QT duration models

Objective To study the role of transmural dispersion of repolarization (TDR) and the relationship between TDR and arrhythmogenesis in the model of short QT syndrome. Methods Pinacidil was used to mimic the model of short QT syndrome in the arterially perfused left ventricular (LV) wedge preparations of rabbits. Standard microelectrode technique was used to record transmembrane action potentials of endocardial, epicardial, and mid-myocardial tissues from rabbit LV wall at the basic cycle length of 1 000 ms. We observe the effect of pinacidil, pinacidil pluse isoproterenol, quinidine and glybenclamide on the 90% action potential duration (APD_ 90 ) and TDR respectively. At the same time an S_2 was applied to investigate the arrhythmogenesis under each condition.Results Pinacidil abbreviated the APD_ 90 of three types cells of LV wall and increased the TDR (58.84±13.42 ms vs 35.26±13.30 ms). Addition of isoproterenol led to greater abbreviation of the APD_ 90 and a further increase in TDR (64.60±21.46 ms vs 58.84±13.42 ms). On both of these two conditions abnormal beats could be induced by premature stimulation. Quinidine and glybenclamide could reverse the effect of pinacidil and reduce the abnormal beats to none. Conclusions The heterogeneous abbreviation of the action potential duration among different cell types spanning the ventricular wall creates the substrate for the genesis of ventricular tachycardia (VT) under conditions associated with short QT intervals. Quinidine can reduce the occurrence of life-threatening ventricular tachycardia/fibrillation through shortening the TDR of left ventricular wall.