Effects of flecainide on contractile force and electrophysiological parameters in cardiac muscle

The action of N-(2-piperidylmethyl)-2,5-bis-(2,2, 2-trifluoroethoxy)-benzamide acetate (flecainide, Tambocor) on contractile force and electrophysiological parameters was studied in isolated calf ventricular fibres. Increasing flecainide concentrations (2-10 mg/l) induced a progressive decrease of force of contraction. At the highest concentration the peak of contraction was reduced by 50-40% of the control value, accompanied by a similar fall of the maximal rate of the rise of contraction (dP/dtmax). The negative inotropic effect was not significantly different at driving frequencies of 0.2 and 1 Hz. 5 mg/l flecainide reduced the tonic as well as the phasic components in high potassium contractures and induced a reduction of the action potential maximal upstroke velocity (Vmax). The suppression of Vmax was augmented by increasing the stimulation frequency from 0.2 to 1 Hz. This frequency dependence could partially be explained by a flecainide induced delay of Vmax recovery from inactivation. Plateau height and duration of the action potential were not significantly effected. The height and duration of slow potentials in 22 mmol/l K+-Tyrode solution were reduced under 5 mg/l flecainide. This effect was frequency independent, since the recovery of the slow potentials from inactivation was not delayed by flecainide. The results indicate that the new antiarrhythmic drug flecainide possesses two different sites of action, indicated by the different frequency dependence on Vmax and slow potential system under flecainide. The observed negative inotropic effect seems to be induced by the depressing effect of flecainide on the slow potential system.