Quantitative analysis of the antiarrhythmic effect of drugs on canine ventricular arrhythmias by the determination of minimum effective plasma concentrations.

Abstract

Antiarrhythmic effects and minimum antiarrhythmic plasma concentrations (min PC) were examined using three canine ventricular arrhythmia models, i.e., two-stage coronary ligation arrhythmia (Cor), halothane-adrenaline arrhythmia (Adr) and digitalis arrhythmia (Dig). Disopyramide suppressed these three arrhythmias and its min PCs were 5.3 +/- 1.8 (Cor), 4.2 +/- 1.1 (Adr) and 1.7 +/- 0.4 micrograms/ml (Dig). Procainamide suppressed coronary ligation arrhythmia and its min PC was 27.1 +/- 4.0 micrograms/ml, but was not effective on adrenaline arrhythmia. Aprindine was effective on three arrhythmias and its min PCs were 1.6 +/- 0.3 (Cor), 1.0 +/- 0.4 (Adr) and 0.8 +/- 0.4 micrograms/ml (Dig). Lidocaine was not effective on coronary ligation arrhythmia, but was effective on adrenaline arrhythmia and its min PC was 15 micrograms/ml. Phenytoin was effective on three arrhythmias and its min PCs were 9.8 +/- 2.0 (Cor), 12.1 +/- 3.1 (Adr) and 11.3 +/- 3.0 micrograms/ml (Dig). It was not specifically effective on canine digitalis arrhythmia. Propranolol and other beta-blockers were effective on adrenaline arrhythmia, but very high doses were necessary for suppressing coronary ligation and digitalis arrhythmias. Verapamil was only effective on adrenaline arrhythmia and its min PC was 0.03 +/- 0.01 microgram/ml. Canine min PCs of drugs were almost the same as those reported in man except for procainamide and lidocaine. Membrane stabilizing effects seem to be important for suppressing canine ventricular arrhythmias.