Effects of flecainide on the cellular electrophysiology of neonatal and adult cardiac fibers

Abstract

The acute cellular electrophysiologic actions of flecainide acetate on isolated neonatal and adult canine ventricular myocardium and Purkinje fibers were evaluated with standard microelectrode techniques. Flecainide, 0.1 to 10.0 micrograms/ml, produced concentration-dependent decreases in action potential amplitude, overshoot, and phase O Vmax of adult ventricular myocardium and Purkinje fibers. The greatest effects were on Vmax. Neonatal action potential characteristics were affected to a lesser degree by flecainide. Flecainide had disparate effects on myocardial and Purkinje fiber repolarization and refractoriness. In adult ventricular myocardium, action potential duration (APD) and effective refractory period (ERP) increased progressively with drug concentration. APD and ERP were increased to a lesser degree in neonatal myocardium. In adult Purkinje fibers, APD decreased progressively with increasing flecainide concentrations. ERP decreased at 0.1 and 1.0 microgram/ml, but returned to control values at 10.0 micrograms/ml. APD and ERP of neonatal Purkinje fibers responded to a lesser degree. At faster stimulation frequencies (2 to 4 Hz), flecainide produced significant frequency-dependent decreases in Vmax in adult Purkinje fibers. Such use-dependency was not evident in neonatal fibers. These data indicate a significantly lower sensitivity of immature cardiac tissues to the electrophysiologic effects of flecainide.