HEMODYNAMIC-EFFECTS OF N-ACETYLPROCAINAMIDE COMPARED WITH PROCAINAMIDE IN CONSCIOUS DOGS

The hemodynamic actions of clinically relevant i.v. doses (20 mg/kg and 10 mg/kg) of n-acetyl procainamide (NAPA) a major metabolite of procainamide which possesses antirhythmic properties, in conscious dogs preinstrumented with a left ventricular (LV) micromanometer, LV and aortic catheters, and ultrasonic crystals for measurement of LV internal diameter shortening (%.DELTA.D). Within 30 s after the 20 mg/kg dose, there were significant increases in heart rate (27 .+-. 7 beats/min, mean .+-. SEM [standard error of the mean]; n = 6), maximum dP/dt [maximum change in pressure over time] (655 .+-. 206 mmHg/s), and %.DELTA.D [% minor diameter shortening] (2.2 .+-. 0.9%; all P .ltoreq. 0.05). By 6 h after the dose there were reductions compared with control in peak LV pressure (19 .+-. 9 mmHg), dP/dt (610 .+-. 210 mmHg/s), and %.DELTA.D (2.3 .+-. 0.6%;all P .ltoreq. 0.05). Equimolar doses of procainamide or drug vehicle alone evoked no response, as did NAPA after pretreatment with reserpine (0.25 mg/kg/day for 2 days) or hexamethonium (10-15 mg/kg). NAPA apparently produces a biphasic hemodynamic response with enhancement of LV performance early and a decrease later; this response is different from that of the parent compound, procainamide. These effects are likely mediated by the adrenergic nervous system at either a ganglionic or a central level.