Sugiyama A, Takehana S, Kimura R, Hashimoto K
Department of Pharmacology, Yamanashi Medical University, Nakakoma-gun, Japan.
Heart Vessels. 1999;14(2):96-103. doi: 10.1007/BF02481749.
The present study was designed to assess the negative chronotropic and inotropic effects of 10 class I antiarrhythmic drugs, using isolated canine blood-perfused sinoatrial node and papillary muscle preparations. Each drug showed negative chronotropic and inotropic effects in a dose-related manner. The potency of the suppressive effect on the sinoatrial automaticity was in the order of aprindine, quinidine, flecainide, lidocaine, mexiletine, cibenzoline, disopyramide, procainamide, tocainide, and phenytoin, while the effect on the ventricular contraction was in the order of aprindine, flecainide, cibenzoline, lidocaine, mexiletine, disopyramide, tocainide, phenytoin, quinidine, and procainamide. The differences in the suppressive effects could not necessarily be explained by their subclassification, based either on action potential duration or kinetic properties of dissociation or association with sodium channels. On the other hand, we found a good correlation between the negative inotropic effects of class I drugs in this study and the canine antiarrhythmic plasma concentrations for the digitalis- and coronary ligation-induced ventricular arrhythmia models in our previous studies. However, the negative chronotropic effects of the drugs showed a poor correlation with the antiarrhythmic plasma drug concentrations. The data shown in this paper may provide a convenient guideline for predicting acute cardiosuppressive effects of antiarrhythmic drugs, especially in patients with reduced cardiac function.
本研究旨在利用离体犬血液灌注的窦房结和乳头肌标本，评估10种I类抗心律失常药物的负性变时和变力作用。每种药物均呈剂量依赖性地表现出负性变时和变力作用。对窦房结自律性抑制作用的强度顺序为：安搏律定、奎尼丁、氟卡尼、利多卡因、美西律、西苯唑啉、丙吡胺、普鲁卡因胺、妥卡尼和苯妥英，而对心室收缩的作用顺序为：安搏律定、氟卡尼、西苯唑啉、利多卡因、美西律、丙吡胺、妥卡尼、苯妥英、奎尼丁和普鲁卡因胺。基于动作电位持续时间或与钠通道解离或结合的动力学特性进行的亚分类，不一定能解释这些抑制作用的差异。另一方面，我们发现在本研究中I类药物的负性变力作用与我们之前研究中洋地黄和冠状动脉结扎诱导的室性心律失常模型的犬抗心律失常血浆浓度之间存在良好的相关性。然而，药物的负性变时作用与抗心律失常血浆药物浓度的相关性较差。本文所示数据可能为预测抗心律失常药物的急性心脏抑制作用提供便利的指导方针，尤其是对心功能降低的患者。
