Encainide is highly effective in suppressing most nonsustained ventricular arrhythmias, but there is evidence that the
drug is less effective and may worsen some arrhythmias, particularly in patients with sustained
ventricular tachycardia. In most patients it is likely that the major antiarrhythmic effects of
encainide are mediated through a potent metabolite, O-demethyl
encainide. The effects of infusions of
saline solution or O-demethyl
encainide on spontaneous ventricular ectopic activity and
ventricular fibrillation (VF) threshold were compared in 25 dogs with a mottled
myocardial infarct produced by transient
coronary occlusion. Plasma levels of the metabolite above 100 ng/ml suppressed (greater than 92%) the spontaneous ventricular ectopic activity that occurred 48 hours after MI, whereas
saline solution had no effect. In 15 dogs treated with O-demethyl
encainide, the VF threshold decreased an average of 23%, from a baseline level of 23 +/- 8 mA to 18 +/- 9 mA (p less than 0.05). There was a concentration-dependent fall in VF threshold with plasma concentrations of O-demethyl
encainide above 150 ng/ml. In 2 dogs with very high plasma concentrations of the metabolite (greater than 1,000 ng/ml), VF was induced by right ventricular pacing alone (S1S1 300 ms). No change in VF threshold was observed in the 8 dogs treated with
saline solution, and in each of these dogs VF could be terminated by the countershock protocol. However, in 7 of the 17 dogs treated with O-demethyl
encainide, VF could not be terminated by the countershock protocol.(ABSTRACT TRUNCATED AT 250 WORDS)