The inotropic actions of N-acetylprocainamide: blockade and reversal by propranolol

The inotropic actions of N-acetylprocainamide (NAPA) were studied in chloralose-urethane anesthetized dogs. Myocardial contractile force was measured with a Walton-Brodie strain gauge sutured to the right ventricle. A low-dose NAPA infusion (12 mg/kg i.v.) increased myocardial force by a maximum of 11.6 +/- 2.4% (mean +/- SEM), whereas a high dose of NAPA (60 mg/kg i.v.) increased myocardial force by 33.3 +/- 2.6% at the peak of the effect. The high-dose NAPA infusion also caused significant reductions in heart rate and blood pressure, while the low-dose NAPA infusion lacked significant chronotropic or hypotensive actions. Pretreatment with propranolol (0.5 mg/kg i.v. loading, followed by a 10 micrograms/kg/min infusion) did not block the positive inotropic actions of NAPA 12 mg/kg, but these actions were blocked in dogs pretreated with both propranolol and atropine (1 mg/kg). On the other hand, pretreatment with propranolol blocked and reversed the inotropic actions of NAPA 60 mg/kg, and potentiated its negative chronotropic effects. Thus, the positive inotropic actions of NAPA are indirect and more than one mechanism is involved; a component due to direct action related to the lengthening of cardiac repolarization is not discounted. At low doses, the increase in myocardial force seems related to NAPA's vagolytic properties, whereas at high doses the positive inotropic actions appear to be catecholamine-mediated. Furthermore, a negative inotropic action of high-dose NAPA is apparent after beta-adrenergic receptor blockade.