Hemodynamic effects of n-acetylprocainamide compared with procainamide in conscious dogs

We examined the hemodynamic actions of clinically relevant i.v. doses (20 mg/kg and 10 mg/kg) of n-acetyl procainamide (NAPA) 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 seconds after the 20-mg/kg dose, there were significant increases in heart rate (27 +/- 7 beats/min, mean +/- SEM; n = 6), maximum dP/dt (655 +/- 206 mm Hg/sec), and % delta D (2.2 +/- 0.9%; all p less than or equal to 0.05). However, by 6 hours after the dose there were reductions compared with control in peak LV pressure (19 +/- 9 mm Hg), dP/dt (610 +/- 210 mm Hg/sec), and % delta D (2.3 +/- 0.6%; all p less than or equal to 0.05). In contrast, 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). These data suggest NAPA 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.