Antiarrhythmic effects of combined application of class I antiarrhythmic drugs; addition of low-dose mexiletine-enhanced antiarrhythmic effects of disopyramide and aprindine in various-rate canine ventricular tachycardias.

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.