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Journal of Pharmacology And Experimental Therapeutics, Vol. 184, Issue 3, 619-630, 1973
Copyright © 1973 by American Society for Pharmacology and Experimental Therapeutics

ELECTROPHYSIOLOGIC EFFECTS OF PHENOTHIAZINES ON CANINE CARDIAC FIBERS

MAKOTO ARITA 1 and BORYS SURAWICZ 1

1 cardiovascular Division, Department of Medicine, University of Kentucky, Lexington, Kentucky

We studied the effect of three concentrations (0.5, 3.0 and 10µg/ml) of chlorprornazine and thioridazine on action potentiais of isolated caniume ventricular muscle and Purkinje fibers driven at rates 0.1 to 4 cps for 30 to 120 minutes. Both drugs. except at high concentrations, did not change the restiumg potential but shifted the curve relating maximum rate of rise (dv/dt) of phase 0 to membrane potential downwards and to the right (decreased membrane responsivelmess) in the Purkinje fibers. In both fiber types. the drugs 1) decreased overshoot, 2) decreased maximum dv/dt of action potentials arising from the resting potential more at rapid than at slow rates (production of dependence of dv/dt on time). 3) decreased duration and amplitude of phase 2 and reduced rate-dependent change in the duration of this phase and 4) prolonged phase 3. All effects were augmented by increasing concentrations and durations of drug action and were more pronouumced in the Purkinje than in the ventricular muscle fibers. Increase in (Na+)o from 148 to 222 mM reversed all effects except the effect on time-dependent dv/dt. Our results indicate that phenothiazines retard the reactivation of the rapid sodium-carrying system and suggest that the drugs decrease the maximum available sodium conductance. The prolongation of phase 3 by phenotimiazines appears to be secondary to shortening of phase 2.

Submitted on June 26, 1972
Accepted on November 29, 1972




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