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Electrophysiological effects of flecainide on guinea pig ventricular muscle in high extracellular potassium concentration acidosis and hypoxia


, : Electrophysiological effects of flecainide on guinea pig ventricular muscle in high extracellular potassium concentration acidosis and hypoxia. Japanese Heart Journal 28(4): 539-554

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 (0.5-1 .mu.g/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 (.ovrhdot.Vmax), which was depressed in a dose-dependent manner. In high [K+] medium (potassium concentration=10 mM), .ovrhdot.Vmax was depressed by 16.8 at a concentration of 1.0 .mu.g/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 15 min, .ovrhdot.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 .ovrhdot.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.

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