Electrophysiologic and hemodynamic effects of propafenone, a new antiarrhythmic agent, on the anesthetized, closed-chest dog: comparative study with lidocaine.

The relative hemodynamic and electrophysiologic effects of a new antiarrhythmic drug, propafenone, and lidocaine were evaluated in eight closed-chest, anesthetized dogs. Propafenone (4 mg/kg intravenously) significantly (p less than 0.05) lowered aortic and pulmonary systolic pressures and caused a rise in heart rate (p less than 0.05). Cardiac output decreased from 4.5 +/- 1 to 3.8 +/- 0.7 L/min (p less than 0.05) during atrial pacing at 400 msec cycle length. Propafenone had no effect on pulmonary and aortic diastolic pressures. Lidocaine (5 mg/kg intravenously) caused a significant (p less than 0.05) decrease in aortic systolic pressure and a rise in heart rate. Lidocaine had no significant effect on the other measured hemodynamic parameters. Propafenone, unlike lidocaine, significantly (p less than 0.05) increased atrioventricular nodal functional refractory period and right ventricular endocardial (apex) cathodal (0.5 +/- 0.1 mA to 1.9 +/- 0.3 mA) and bipolar (1.4 +/- 0.3 to 2.2 +/- 0.4 mA) diastolic excitability threshold. Propafenone, unlike lidocaine, also caused a significant (p = 0.05) intraatrial conduction delay; however, neither drug caused conduction slowing in the His-Purkinje system. Both drugs had no effect on sinus nodal recovery time and on the effective refractory period of the right ventricular endocardium (apex). Mean plasma propafenone levels during hemodynamic and electrophysiologic measurement ranged between 3.2 +/- 1.8 micrograms/ml and 1.7 +/- 1.1 micrograms/ml. All of the propafenone-induced effects were reversible within 90 minutes. We conclude that propafenone differs from lidocaine in its atrial, AV nodal, and ventricular electrophysiologic properties, and thus these may explain propafenone's greater efficacy over lidocaine against both certain atrial and ventricular arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)