Test of a model of antiarrhythmic drug action. Effects of quinidine and lidocaine on myocardial conduction.

Abstract

The effects of quinidine and lidocaine on the maximum upstroke velocity (Vmax) of the ventricular myocardial action potential were compared with the effects predicted by a model over a wide range of driving rates, rhythm disturbances and holding potentials. These rate-, rhythm- and voltage-dependent effects were accurately predicted by the proposed model. The model was also able to predict several previously undocumented properties of the drugs: 1) If lidocaine decreases Vmax of a pulse train, the steady state is reached within a few action potentials. 2) The poststimulation recovery of Vmax in the presence of lidocaine or quinidine can occur in a multiexponential fashion, if the membrane potential is kept at the potential where both the fast (operating mainly at more negative membrane potentials) and the slow (operating at more positive potentials) recovery processes are operative. 3) Hyperpolarization markedly attenuates the rate-dependent drug effects. 4) Combinations of lidocaine and quinidine have a superadditive effect on the Vmax of early extrasystoles.