Frequency-dependent effects of class I, III and IV antiarrhythmic drugs on the conduction and excitability in rabbit ventricular muscle.

The frequency-dependent effect of 11 antiarrhythmic drugs on the impulse conduction time and excitability threshold was studied in isolated rabbit right ventricular muscle. Before drug application, conduction time and excitability threshold were independent of the stimulation cycle length (200-2000 msec). Quinidine, tocainide, lidocaine, disopyramide, procainamide, flecainide, lorcainide and mexiletine increased conduction time and excitability threshold in a frequency-dependent manner (use-dependency) while verapamil, clofilium and bretylium did not significantly alter conduction and excitability at any applied stimulation frequency. It was concluded that the use-dependent effect which was described earlier with most Class I antiarrhythmic drugs on the rate of rise of the action potential can be also demonstrated in extracellular electrophysiological experiments and this must be considered during routine pharmacological screenings.