Electropharmacodynamics of N-Acetylprocainamide in the Immature Mammalian Heart - Evidence for a Prominent Class III Effect in the Newborn

Abstract

The electrophysiologic effects of N-acetylprocainamide (NAPA), a metabolite of procainamide reported to exert significant Class III antiarrhythmic effects in the adult heart, were evaluated in 12 neonatal mongrel canines (ages 7-14 days). Following transvascular placement of quadripolar electrical catheters in the right atrium and ventricle, and a tripolar catheter in the region of the His bundle, electrophysiologic assessments were made of sinus and AV nodal function and atrial and ventricular refractoriness utilizing intracardiac stimulation and recording techniques following cumulative intravenous doses of 20 and 40 mg/kg of NAPA (serum concentrations 13.1 +/- 1.9 and 25.6 +/- 3.4 micrograms/ml). NAPA resulted in an overall increase in sinus cycle length of 18%. No changes were observed in the paced cycle length resulting in AV nodal Wenckebach. Consistent with NAPA's reported Class III action, NAPA increased the effective and functional refractory periods of the ventricle by 35 and 34%, respectively (p less than 0.001). Even larger increases were observed in atrial refractoriness (effective 75%, functional 57%, p less than 0.001). In separate experiments (n = 6), the effects of intravenous NAPA (40 mg/kg) on the duration of the monophasic action potential recorded from the neonatal atrium and ventricle were determined. NAPA increased APD90 of the atrium by approximately 50% and that of the ventricle by 60%, thus confirming a significant effect on myocardial repolarization in the neonate.