Hashimoto K
Department of Pharmacology, Yamanashi Medical College, Japan.
Nihon Yakurigaku Zasshi. 1989 Feb;93(2):29-39. doi: 10.1254/fpj.93.29.
In order to compare and clarify the effects of various antiarrhythmic drugs, we examined drug effects on several canine arrhythmia models, simultaneously determining the minimum effective plasma concentrations. We used 1) two-stage coronary ligation arrhythmia, 2) digitalis arrhythmia, and 3) halothane-adrenaline arrhythmia. The following are, a summary of our results: Antiarrhythmic drugs of class 1 all suppressed digitalis arrhythmia, and except for lidocaine, also suppressed coronary ligation arrhythmia. Class 2 antiarrhythmic drugs, beta blockers, and class 4 antiarrhythmic drugs, Ca channel blockers, had common features of effectiveness, where they suppressed adrenaline arrhythmia in relatively low concentrations. Some differences among the antiarrhythmic effects of class 1 drugs could not be explained by their subclassification based either on action potential duration or kinetic properties of dissociation or association with Na channels. A new arrhythmia model for triggered activity in in vivo canine heart was developed, but drug effects on it does not seem to be very different from the effects on the other three arrhythmia models.
为了比较和阐明各种抗心律失常药物的作用,我们研究了药物对几种犬心律失常模型的影响,同时测定最低有效血浆浓度。我们使用了:1)两阶段冠状动脉结扎心律失常模型;2)洋地黄心律失常模型;3)氟烷 - 肾上腺素心律失常模型。以下是我们的结果总结:Ⅰ类抗心律失常药物均能抑制洋地黄心律失常,除利多卡因外,也能抑制冠状动脉结扎心律失常。Ⅱ类抗心律失常药物(β受体阻滞剂)和Ⅳ类抗心律失常药物(钙通道阻滞剂)具有共同的有效性特征,即在相对低浓度时就能抑制肾上腺素心律失常。Ⅰ类药物抗心律失常作用的一些差异,无法用基于动作电位时程或与钠通道解离或结合的动力学特性进行的亚分类来解释。我们建立了一种新的体内犬心脏触发活动心律失常模型,但药物对其的作用似乎与对其他三种心律失常模型的作用没有太大差异。