奎尼丁相关性尖端扭转型室性心动过速机制的实验研究

目的　在低钾时观察不同浓度QUI对 3层心肌细胞复极和跨室壁复极离散度 (TDR)的影响及致EAD ,TdP的情况 ,以探讨QUI致TdP的发生机制。方法　采用Langen dorff技术离体兔心脏灌流。于不同起搏周长同步记录不同浓度QUI(1、5、1 0 μmol·L- 1 ) +低钾 (1 5mmol·L- 1 )作用时3层心肌MAP ,观察并记录EAD及诱发TdP的情况。结果　 (1 )QUI浓度依赖性地延长三层心肌MAPD90 ,其中对中层心肌作用最明显。 (2 )QUI逆浓度依赖性、逆频率依赖性地增大TDR。在 1 50 0ms起搏频率 ,低、中、高浓度QUI组及对照组TDR分别为 (83± 1 1 )、(74± 1 2 )、(68± 1 1 )及 (47± 7)ms。 (3)各浓度QUI组均频繁出现EAD ,各组间对比无差异 (P >0 0 5)。而低、中、高浓度QUI组TdP发生率分别为 5/1 0、3/9、1 /9。TDR的变化与TdP的发生相关。结论　QUI导致兔心脏跨室壁复极离散的增大 ,是其诱发TdP产生的主要机制

Experimental study on the mechanism of quinidine induced torsade de pointes in rabbit heart

AIM To enhance our understanding of the mechanism of torsade de pointes (TdP) caused by quinidine (QUI), we studied its effect on repolarization of epicardial, midmyocardial (M), and endocardial tissues in rabbits. METHOD Monophasic action potential techniques were used to study the effects of QUI 1,5,10 μmol·L -1 on APD in three layer myocardium of left ventricle at cycle lengths (CLs) from 400 to 1 500 ms in hypokalemic tyrode's solution perfused rabbit heart. The early afterdepolarization (EAD) and TdP were observed as well. RESULTS (1) QUI induced concentration and reverse rate dependent prolongation of MAPD 90 in all the three ventricular myocardium. The effects of QUI on M cell is more prominent. (2) QUI augmented TDR in reverse concentration and reverse rate dependent fashion. At CL of 1 500 ms, the TDR values of 1,5,10 μmol·L -1 QUI and control group were (83±11), (74±12), (68±11), and (47±7) ms respectively. (3) There were consistent high incidence of EAD in all QUI groups. However, the occurrence of TdP in 1 0, 5 0, 10 0 μmol·L -1 QUI groups were 5/10, 3/9, 1/9 respectively. There was a close correlation between TDR and TdP.CONCLUSION QUI induces prominent augmentation of TDR which is a major mechanism of the development of TdP in rabbit heart.