Effect of lidocaine and quinidine on steady state characteristics and recovery kinetics of (dV/dt)max in guinea pig ventricular myocardium

Abstract

We studied the effects of quinidine and lidocaine on the steady state relationship between membrane potential and the maximum rate of rise of the action potential, (dV/dt)(max), and on the recovery kinetics of (dV/dt)(max) in guinea pig papillary muscles. The steady state relationships were determined in fibers stimulated at 0.2/sec and depolarized with KCl. Recovery kinetics were determined at various resting membrane potentials by assessing (dV/dt)(max) in progressively earlier premature action potentials. Lidocaine caused a dose dependent decrease in (dV/dt)(max), shifted the curve defining the steady state relationship along the voltage axis in the direction of more negative potentials, and slowed the recovery kinetics of (dV/dt)(max). Quinidine caused a dose dependent decrease in (dV/dt)(max) but did not alter the shape of the curves defining either the steady state relationship or the recovery kinetics of (dV/dt)(max). Both drugs depressed membrane responsiveness as determined in premature action potentials originating from incompletely repolarized fibers. Our study indicates that the mechanisms whereby quinidine and lidocaine influence (dV/dt)(max) are different. It is possible that this difference may underlie some of the differences in the clinical effects of these two drugs.