Electrophysiologic antagonism of quinidine and bretylium tosylate

Abstract Interactions of quinidlne (5 mg/liter) and bretylium tosylate (20 mg/ liter) were studied in isolated perfused rabbit hearts by recording transmembrane potentials from the atrial fibers, the atrioventricular (A-V) junction and the ventricular fibers. The following observations were made on ventricular fibers. As expected, administration of quinidine prolonged action potential duration and reduced the maximal rate of depolarization. Subsequent addition of bretylium to quinidine shortened action potential duration and tended to restore the maximal rate of depolarization. The membrane resting potential, the action potential amplitude and overshoot showed no significant changes. With respect to A-V conduction, bretylium alone shortened intraatrial and His-Purkinje conduction times but prolonged intranodal conduction time. With quinidine, intraatrial and His-Purkinje conduction times were markedly prolonged and intranodal conduction time was only slightly increased. Addition of bretylium to quinidine shortened intraatrial and His-Purkinje conduction times but significantly prolonged intranodal conduction time, resulting in a further prolongation of the total A-V interval. The possible clinical implications of these findings are stressed.