ELECTROPHYSIOLOGIC EFFECTS OF BRETYLIUM TOSYLATE ON SINGLE FIBERS OF THE CANINE SPECIALIZED CONDUCTING SYSTEM AND VENTRICLE

¹ Cardiopulmonary Laboratory, U.S. Public Health Service Hospital, Staten Island, New York

The effects of bretylium tosylate were determined on the transmembrane action potentials of canine Purkinje fibers and ventricular muscle fibers from normal and reserpine-pretreated dogs, and on fibers after perfusion with tyramine. Bretylium prolonged action potential duration and effective refractory period at the concentrations studied in all groups. Maximum diastolic potential, dv/dt of phase zero and Purkinje fiber conduction velocity were not affected in the majority of studies. Several Purkinje fibers with low resting potentials from normal dogs were transsiently hyperpolarized, resulting in an increase in dv/dt and conduction velocity. This effect was never seen in fibers from reserpine-pretreated dogs or after tyramine perfusion. In Purkinje fibers from normal dogs, bretylium produced an initial increase in automaticity, which was later followed by a return to either control frequency or slightly below. This initial increase could be prevented by beta receptor blockade and was not seen in fibers from reserpine-pretreated dogs. Perfusion with tyramine also decreased this initial effect on automaticity. Bretylium did not shift the membrane response curve of Purkinje fibers except at the highest concentration studied. Bretylium thus has several elctrophysiologic effects that are different from those of antiarrhythmic drugs in present use. Some of its effects can be explained on the basis of catecholamine release, probably from nerve terminals in the preparation.