Abstract

The effect of encainide and its two major metabolites, O-demethylated encainide (MJ 9444) and 3-O-methoxy encainide (MJ 14030), on cardiac conduction was studied by recording His bundle potentials in isolated perfused rabbit hearts and Purkinje and muscle conduction in vivo in dog hearts after destruction of the atrioventricular node. Both metabolites are 4 to 15 times more potent than encainide in slowing conduction through the atria, the AV-node and the His-Purkinje system of the rabbit heart. They did not differ from each other in potency but MJ 9444 increased the duration and decreased the height of the ventricular potential whereas MJ 14030 had no effect at doses which caused conduction block. In the dog, encainide (0.8-3.2 mg/kg i.v.) slowed conduction of extrasystoles in both Purkinje and muscle at all coupling intervals, increased the effective refractory period and the functional refractory period of the Purkinje pathway. MJ 9444 (0.05-0.4 mg/kg) speeded Purkinje conduction of early (less than 300 msec) without affecting or while slowing conduction of late (greater than 350 msec) extrasystoles. Higher doses (0.4-1.6 mg/kg) slowed conduction at all intervals. The effective refractory period and the functional refractory period were decreased but in some cases returned to control values at the higher doses. Muscle conduction was slowed at doses of 0.4 mg/kg or more. MJ 14030 (0.05-3.2 mg/kg) had variable effects, behaving like MJ 9444 in three experiments but like the parent compound in two others. Only slowing of conduction was seen with the three drugs when heart rate was changed.(ABSTRACT TRUNCATED AT 250 WORDS)