The Hemodynamic Actions of N-Acetylprocainamide in Dogs: Kinetics of Effects and Plasma Concentration-Response Relationships 1

Summary

The hemodynamic actions of N-acetylprocainamide (NAPA) were investigated in anesthetized, open chest dogs. NAPA pharmacokinetics and effects were correlated for 2 hr after a 15-min NAPA infusion (60 mg/kg) to five nonpaced dogs and four cardiac-paced dogs. Four control dogs received NAPA diluent for comparison. NAPA infusion in nonpaced dogs decreased mean arterial pressure (MAP) by 26.5 ± 7.1% (mean ± SE) and total peripheral resistance (TPR) by 15.0 ± 3.7%, but increased myocardial contractile force (MCF) by 33.5 ± 7.5% and reduced heart rate 18.5 ± 3.2%. Significant differences from controls persisted 18, 28, 32, and 60 min for MCF, MAP, TPR, and heart rate, respectively. The changes in TPR were multiphasic and appeared to result from a combination of drug-induced vasodilation and compensatory reflex vasoconstriction. In NAPA-paced dogs, MCF was increased similarly by 31.6 ± 5.3%. MAP and TPR decreased by 33.5 ± 5.3 and 29.1 ± 11.8%, respectively. The magnitude and duration of the latter effects (75 and 50 min, respectively) were greater and cardiac output better maintained than in NAPA-nonpaced dogs. This effect on cardiac output probably accounts for a lack of compensatory vasoconstriction in NAPA-paced dogs. NAPA infusion did not consistently change left ventricular end diastolic pressure. However, consistent NAPA plasma concentration-response relationships were observed for MCF, MAP, TPR, and heart rate: thus, we conclude that NAPA is a vasodilator that has negative chronotropic and positive inotropic effects. The mechanisms of these actions require elucidation.

The authors wish to thank Dr. Arthur J. Atkinson, Jr. for advice and encouragement. Ms. Nancy Peterson's help preparing the manuscript is greatly appreciated.