Electrophysiological Actions of a New Antiarrhythmic Agent on Isolated Preparations of the Canine Purkinje Fiber and Ventricular Muscle

Abstract

The electrophysiological actions of a new antiarrhythmic drug [Kö1173, or 1-methyl-2-(2,6-xylyloxy)ethylamine hydrochloride] with a chemical structure similar to that of lidocaine, were investigated with an isolated canine preparation consisting of the right bundle branch and its attached ventricular muscle. At concentrations of less than 5 µg/ml conductivity in the Purkinje fibers or in the ordinary ventricular muscle was hardly affected by this drug, but conduction across the Purkinje fiber-muscle junction (P-M junction) was markedly depressed and blockage of conduction was often observed. Action potential durations of the Purkinje fibers were consistently shortened and the effective refractory period of the Purkinje fibers was also decreased at concentrations of 5 µg/ml or less. Over a range of concentrations from 2 to 20 µg/ml, spontaneous activity and the slope of phase 4 depolarization in the Purkinje fibers were significantly decreased. These results suggest that the electrophysiological action of Kö1173 resembles that of lidocaine, but include suppressive effects on conduction across the P-M junction at the concentration of 5 µg/ml.