Comparative Effects of Procainamide and Its N-Acetylated Metabolite in Conscious Dogs with Atrioventricular Block

Abstract

The effects of procainamide and its metabolite N-acetylprocainamide (NAPA) on atrial effective refractory period (AERP), atrial rate, ventricular rate, and mean blood pressure were investigated in conscious dogs with chronic atrioventricular block and implanted atrial pacing electrodes. Procainamide at cumulative doses of 4.3, 13.0, and 30.3 mg/kg and NAPA at equimolar doses of 5.1, 15.3, and 35.7 mg/kg (i.e., at plasma levels covering the assumed therapeutic range) concentration-relatedly lengthened AERP, as reflected by the decrease of maximal atrial frequency determined by pacing. Procainamide was 1.2-1.5 times more potent than NAPA in this regard. Both drugs increased atrial rate in relation to their plasma concentrations--procainamide 1.2 times more than NAPA. Procainamide decreased ventricular rate at the two highest doses, while NAPA decreased it only at the highest dose after having increased it at the lowest. Procainamide lowered mean blood pressure at the lowest dose and increased it 15 min after the highest, whereas NAPA produced an increase in mean blood pressure for each dose. Taken together, these results on atrial rate, ventricular rate, and mean blood pressure indicate that the two drugs possess distinct pharmacological properties--i.e., procainamide exhibits slightly more marked direct vagolytic and depressor effects than does NAPA and exerts quite different blood pressure effects from those of NAPA. Thus, these data suggest that NAPA, especially when present at high levels, may markedly affect expected responses in patients being treated with procainamide.