Anesthetized Dogs: Concentration-Response Relationships

The electrophysiologic effects of n-acetylprocainamide (NAPA) and procainamide (PA) were compared in 14 chloralose-anesthetized dogs using intracardiac electrography and programmed stimulation. With five successive sequences of an intravenous bolus followed by a 45-minute infusion, plasma concentrations (Cp) ranged from 1.8 ± 0.1 to 32 ± 2 g/ml for PA and from 8.2 ± 0.3 to 125 i 7 ,ug/ml for NAPA. In three control dogs, mean aortic pressure (BP), heart rate (SCL), sinus node recovery time (SNRT), conduction times (ah, HV and QRS), ventricular repolarization time (QT,), Wenckebach cycle length (WCL) and atrial, nodal and ventricular refractory periods (RP) had a mean coefficient of variation < 9%. Neither drug significantly changed BP and sinus node automaticity (SCL or SNRT). PA was considerably more effective than NAPA in producing a Cp-dependent increase of conduction times. NAPA exerted limited effect only on HV (max increase 13 ± 3.3% [SEMI at Cp = 125 ± 7 gg/ml). NAPA and PA were equally effective in producing parallel Cp-dependent increases of QTc and WCL. Atrial RPs were prolonged by both drugs with parallel Cp response curves and PA was slightly more potent than NAPA. The PA Cp-dependent increase of nodal functional RP was greater than the effects of NAPA and the Cp-response curves were not parallel. Both drugs increased ventricular RP. The maximum effect of PA always occurred at the highest drug concentration, while the peak effect of NAPA on some measured parameters occurred during the postinfusion decay period. We conclude that in addition to differences in pharmacokinetics NAPA and PA may have different mechanisms of action, different effective antiarrhythmic concentrations and different electrical cardiac tox-