Electrophysiological Effects of Flecainide on Guinea Pig Ventricular Muscle in High [K+]o, Acidosis and Hypoxia

摘要

The electrophysiological effects of flecainide on the action potential were examined in guinea pig ventricular muscles using microelectrode recording methods. Under the control conditions, flecainide (0.5-1μg/ml) did not alter the resting potential, action potential duration (APD) or effective refractory period (ERP). The major effect of flecainide was on maximum upstroke velocity (Vmax), which was depressed in a dose-dependent manner. In high [K+] medium (potassium concentration=10mM), Vmax was depressed by 16.8% at a concentration of 1.0μg/ml (8.8% in normal [K+]o). In metabolic acidosis (pH=6.89), it was depressed by 15.7% at the same concentration of the drug (8.3% in normal condition). The changes in ERP and ERP/APD90% in high [K+]o and metabolic acidosis were not significantly different from the normal condition. After hypoxic perfusion for 15min, Vmax depression by flecainide was 16.3% (7.4% in control medium). The increase of ERP/APD90%, was also greater in hypoxia. These data indicate that the most prominent effect of flecainide is Vmax depression which is enhanced under the high K+, acidic and hypoxic conditions. Therefore, it is suggested that flecainide may be most effective for ventricular arrhythmias occurring in myocardial ischemia.