Effect of flecainide on action potentials and alternating current-induced arrhythmias in mammalian myocardium.

The new antiarrhythmic drug flecainide (2,5-bis-(2,2,2-trifluoroethoxy)-N-(2-piperidylmethyl) benzamide acetate) increases action potential duration at 30 and 90% repolarization, and functional refractory period in guinea pig papillary muscle up to 10 mumol/L, but shortens the action potential and decreases its amplitude at 30 mumol/L, without significant change in resting potential. 10 mumol/L flecainide decreases maximal upstroke velocity (Vmax) by about 40% at a stimulation rate of 1 Hz, whereas at 0.017 Hz Vmax remains nearly unchanged (use-dependence). Flecainide delays recovery from inactivation of the fast-sodium channels. Its potential-dependent action on Vmax is demonstrated by a shift to more negative potentials of the membrane responsiveness curve and of the curve that relates membrane potential to Vmax in K+ depolarized papillary muscles driven at 0.017 Hz (h infinity -curve). Flecainide increases threshold of alternating current-induced arrhythmia and asystole in left atria and papillary muscles to a similar extent, and in this respect resembles the local anesthetics. Force of contraction of atrial and ventricular myocardium is significantly decreased at greater than or equal to 10 mumol/L flecainide, and frequency of spontaneously beating right atria at greater than or equal to 0.3 mumol/L. The results indicate that the predominant action of flecainide consists of a potent inhibition of cardiac fast sodium channels.