Cardiac electrophysiological effects of cibenzoline in the conscious dog: plasma concentration-response relationships

The cardiac electrophysiological effects of cibenzoline were studied in the conscious dog. Sinus rate, corrected sinus recovery time (CSRT), and Wenckebach point (WP) were measured in six intact dogs. Atrial and ventricular rates, and atrial effective refractory period (AERP) were measured in seven atrioventricular (AV)-blocked dogs. In both groups, blood pressure and cibenzoline plasma concentrations were also monitored. Each dog received three intravenous injections of 0.75, 1.5, and 3 mg base/kg cibenzoline 30 min apart. Cibenzoline increased sinus and atrial rates from the second dose onward, and ventricular rate slightly at the third dose. It lengthened CSRT and decreased WP at the first two doses only, and increased AERP from the first dose onward. In both groups, cibenzoline increased mean blood pressure at each dose. Taken together, these results indicate that in the conscious dog, cibenzoline at low plasma concentrations exhibits electrophysiological effects (lengthening of CSRT and AERP, and decrease in WP) attributable to its antiarrhythmic properties, and that at increasing concentrations it produces effects (increase in sinus rate, no effect on CSRT nor WP) which reflect competition between the effects related to its antiarrhythmic properties and those resulting from its direct vagolytic effect.