Effects of propafenone on sinus nodal and ventricular automaticity: in vitro and in vivo correlation.
The electrophysiologic effects of the new antiarrhythmic drug, propafenone, were evaluated in anesthetized closed-chest dogs and on isolated cardiac tissues with the microelectrode technique. Propafenone (2 to 4 mg/kg intravenously) had no effect on sinus rate or on sinus nodal recovery time, but caused a dose-dependent significant decrease in the rate of idioventricular rhythm and increased the duration of ventricular overdrive suppression in dogs (n = 8) with complete atrioventricular block. On isolated canine Purkinje fibers (n = 8) manifesting automaticity with resting membrane potential less negative than -70 mV, propafenone reduced the slope of phase 4 depolarization and reduced the rate of automatic impulse initiation in a concentration-dependent manner (10(-6) M-4.10(-5) M). At these concentrations, propafenone had no effect on rabbit sinus nodal automaticity (n = 8) or on sinoatrial conduction. However, significant depression of sinus nodal automaticity occurred with propafenone concentrations above 5.10(-6) M in the presence of cholinergic or complete autonomic blockade with atropine (10(-6) M) and propranolol (5.10(-5) M). Propafenone caused a concentration-dependent decrease in the disparity of Purkinje fiber-ventricular muscle action potential duration (APD), mainly by shortening Purkinje fiber APD. We conclude: that propafenone suppresses idioventricular rhythm in the intact dog, most likely by depressing Purkinje fiber automaticity; the depressant effect of propafenone on sinus nodal automaticity is evident only during cholinergic receptor blockade; and the antiarrhythmic properties of propafenone may include removal of APD disparity by selective shortening of Purkinje fiber and not of ventricular muscle APD.
D000818:Animals; D004285:Dogs; D005260:Female; D006327:Heart Block; D006339:Heart Rate / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D011405:Propafenone / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects / Q000502:physiology; D016276:Ventricular Function
D011405:Propafenone