Awaji T, Hashimoto K
Department of Pharmacology, Yamanashi Medical College, Japan.
J Cardiovasc Pharmacol. 1993 Jun;21(6):960-6. doi: 10.1097/00005344-199306000-00017.
We examined the possible beneficial effects of combined application of class I drugs using digitalis-induced and two-stage coronary ligation-induced canine ventricular arrhythmia models. Combination treatment with disopyramide (0.3 mg/kg/min for 10 min) and mexiletine (0.3 mg/kg/min for 5 min) enhanced the antiarrhythmic effect of a single treatment of disopyramide (0.3 mg/kg/min for 10 min). Combination treatment with aprindine (0.1 mg/kg/min for 10 min) and mexiletine (0.3 mg/kg/min for 5 min) enhanced antiarrhythmic effects of a single treatment of aprindine (0.1 mg/kg/min for 10 min) on digitalis and 24-h two-stage coronary ligation-induced arrhythmia models, but in the 48-h two-stage coronary ligation-induced arrhythmia model, a slow ventricular tachycardia (VT) model, addition of mexiletine to aprindine caused no enhancement of antiarrhythmic effects. The results support those of a previous electrophysiologic study of combination treatment with class I drugs in which disopyramide and mexiletine acted additively but aprindine and mexiletine did not act additively when the ventricular preparation was driven at slow rates. Total heart rate (HR) and mean blood pressure (MAP) were not influenced by additional application of mexiletine.
我们使用洋地黄诱导和两阶段冠状动脉结扎诱导的犬室性心律失常模型，研究了I类药物联合应用可能产生的有益效果。丙吡胺（0.3mg/kg/min，持续10分钟）和美西律（0.3mg/kg/min，持续5分钟）联合治疗增强了丙吡胺单次治疗（0.3mg/kg/min，持续10分钟）的抗心律失常作用。茚满丙二胺（0.1mg/kg/min，持续10分钟）和美西律（0.3mg/kg/min，持续5分钟）联合治疗增强了茚满丙二胺单次治疗（0.1mg/kg/min，持续10分钟）对洋地黄和24小时两阶段冠状动脉结扎诱导的心律失常模型的抗心律失常作用，但在48小时两阶段冠状动脉结扎诱导的心律失常模型（一种缓慢型室性心动过速模型）中，在茚满丙二胺基础上加用美西律并未增强抗心律失常作用。这些结果支持了先前关于I类药物联合治疗的电生理研究结果，即在心室标本以缓慢频率驱动时，丙吡胺和美西律具有相加作用，但茚满丙二胺和美西律没有相加作用。额外应用美西律对总心率（HR）和平均血压（MAP）没有影响。
