CARDIAC ELECTROPHYSIOLOGICAL EFFECTS OF PROPAFENONE AND ITS 5-HYDROXYLATED METABOLITE IN THE CONSCIOUS DOG

We studied the cardiac electrophysiological effects of propafenone and its 5-hydroxylated metabolite in conscious dogs. Sinus rate, correcte d sinus recovery time and Wenckebach point were measured in 6 intact d ogs. Atrial rate, ventricular rate and atrial effective refractory per iod were measured in 6 atrioventricular-blocked dogs. In both groups, we also determined blood pressure and plasma drug concentrations. Each dog received, with at least an 8-day interval, propafenone (hydrochlo ride) and 5-hydroxypropafenone (hydrochloride) in 4 successive intrave nous injections, 30 min apart, at 0.5, 0.5, 1 and 2 mg kg(-1). Propafe none increased sinus rate and atrial rate more markedly than 5-hydroxy propafenone, and also transiently ventricular rate, whereas 5-hydroxyp ropafenone decreased it weakly. Propafenone shortened corrected sinus recovery time and increased Wenckebach point at the highest dose only, whereas 5-hydroxypropafenone did not modify corrected sinus recovery time and increased Wenckebach point less markedly than propafenone. Bo th drugs produced an identical atrial effective refractory period leng thening. Propafenone either increased mean blood pressure (in intact d ogs) or decreased it (in atrioventricular-blocked dogs) at the highest dose only, whereas 5-hydroxypropafenone did not produce any effect on this parameter. Overall, these results show that propafenone and 5-hy droxypropafenone exhibit cardiac electrophysiological effects, reflect ing (a) direct vagolytic action for both drugs associated with cardiod epressant effects for 5-hydroxypropafenone, and (b) marked atrial anti arrhythmic properties for 5-hydroxypropafenone probably involved in th e therapeutic effect of propafenone.