Effects of flecainide on the electrophysiologic properties of isolated canine and rabbit myocardial fibers

Abstract

The electrophysiologic properties of flecainide, a new potent antiarrhythmic drug, are poorly defined. In this study, they were investigated by standard microelectrode technique in isolated cardiac muscle from rabbit and dog hearts. The concentrations of flecainide used were between 0.1 and 10.0 micrograms/ml. Flecainide produced a concentration-dependent decrease in maximal rate of rise of phase 0 of the action potential (Vmax), action potential amplitude and overshoot potential with an increase in the effective refractory period in ventricular muscle. Vmax was reduced by 52.5% after 1 microgram/ml of flecainide (p less than 0.001) and by 79.8% after 10.0 micrograms/ml (p less than 0.001). The corresponding values for Purkinje fibers were 18.6% (p less than 0.01) and 70.8% (p less than 0.001), respectively, but in these fibers the effective refractory period was shortened at the lower concentration and restored to control value at the higher concentration. The depression of Vmax by flecainide was frequency-dependent. The action potential duration was lengthened by flecainide in ventricular muscle and shortened in Purkinje fibers. At high concentrations (10 micrograms/ml), flecainide depressed slow channel-dependent fibers. Purkinje fiber automaticity induced by isoproterenol was slowed by flecainide. The data indicate that the overall electrophysiologic effects of flecainide in isolated cardiac muscle are complex with a major depressant action on Vmax that may account for its dominant antiarrhythmic effects. It is also possible that the differential effects of the compound on the action potential duration and refractoriness in ventricular muscle and Purkinje fibers contribute to the known arrhythmogenic potential of the drug.