ELECTROPHYSIOLOGIC EFFECTS OF 3-(p-CHLOROPHENYL)-(2-IMADAZOLIN-2-YL-METHYL)-1,2,3,4-TETRAHYDRO-1-BENZEPINE HYDROCHLORIDE (SU-13197), A NEW ANTIARRHYTHMIC AGENT

¹ Cardiovascular Section, Department of Medicine, Hahnemann Medical College and Hospital, Philadelphia, Pennsylvania

The electrophysiologic effects of a new potent antiarrhythmic compound capable of reverting atrial flutter and fibrillation were studied in 32 isolated perfused rabbit hearts. Transmembrane potentials were recorded from atrial, atrio-ventricular junctional, Purkinje and ventricular fibers with glass microelectrodes, with appropriate electrograms. The following observations were made at a dose range of 0.6 to 2.0 mg/liter. In atrial, Purkinje and ventricular fibers, the action potential amplitude and the rate of depolarization showed an initial increase with subsequent decrease. The action potential duration was initially unchanged and later prolonged. Prolongation of the effective refractory period and elevation of the diastolic excitability threshold were demonstrated in atrial and ventricular muscle. In the spontaneously beating heart, the sino-atrial rate was consistently decreased. Delay of conduction and failure of propagation were observed in all portions of the atrio-ventricular transmission system (intraatrial, intranodal and subnodal regions). The action potential amplitude was decreased whereas the action potential duration was increased in the atrio-ventricular junctional fibers. Prolonged perfusion with high concentration of this agent often resulted in ventricular standstill, most probably because of suppression of automaticity. SU-13197 appears unique in that it shows both digitalis-like and quinidine-like actions on cardiac electrophysiology.