Tsuchihashi K, Curtis M J
Department of Pharmacology, King's College, University of London, U.K.
J Cardiovasc Pharmacol. 1991 Sep;18(3):445-56. doi: 10.1097/00005344-199109000-00018.
We examined the effects of tedisamil on ventricular fibrillation (VF) elicited by regional ischemia and by reperfusion in isolated rat hearts (n = 12/group). During 30 min of ischemia, 0.1, 0.55, and 3 microM tedisamil had no influence on the incidence of VF (an index of VF initiation). However, sustained VF (SVF, defined as that lasting greater than 120 s, an index of VF maintenance) was reduced in a concentration-dependent manner from 73 to 54, 17 (p less than 0.05), and 0% (p less than 0.05), respectively. Tedisamil caused sinus bradycardia but this was not the basis for tedisamil's antiarrhythmic activity since SVF was also inhibited in separate groups of hearts that were paced throughout the study. Tedisamil had no effect on reperfusion-induced VF initiation. However, VF maintenance was, again, inhibited, with SVF incidence reduced from 75% to 40, 20, and 0% (p less than 0.05), respectively, by increasing concentrations of tedisamil. A similar effect was, again, observed in paced hearts. The average cycle length of the electrogram during VF correlated with preceding width of the ventricular complex; both of these variables were concentration-dependently increased by tedisamil and mean values of each correlated inversely with the incidence of SVF. The ratio of SVF cycle length to ventricular tachycardia cycle length was 1:3, and this ratio was conserved in the presence and absence of drug. The data are consistent with a drug-induced increase in the probability of spontaneous termination of multiple wave-front re-entry.
我们研究了替地沙米对离体大鼠心脏（每组n = 12）局部缺血及再灌注诱发的室颤（VF）的影响。在30分钟的缺血期间，0.1、0.55和3微摩尔的替地沙米对室颤发生率（室颤起始指标）无影响。然而，持续性室颤（SVF，定义为持续超过120秒，室颤维持指标）以浓度依赖方式分别从73%降至54%、17%（p < 0.05）和0%（p < 0.05）。替地沙米引起窦性心动过缓，但这并非替地沙米抗心律失常活性的基础，因为在整个研究过程中进行起搏的另一组心脏中，SVF也受到抑制。替地沙米对再灌注诱发的室颤起始无影响。然而，室颤维持再次受到抑制，随着替地沙米浓度增加，SVF发生率分别从75%降至40%、20%和0%（p < 0.05）。在起搏心脏中再次观察到类似效应。室颤期间心电图的平均周期长度与之前心室复合波宽度相关；这两个变量均随替地沙米浓度依赖性增加，且各自的平均值与SVF发生率呈负相关。SVF周期长度与室性心动过速周期长度之比为1:3，且在有药和无药情况下该比例保持不变。这些数据与药物诱导多波前折返自发终止概率增加一致。
