Interval-dependent effects of lidocaine on conduction in canine cardiac Purkinje fibers: experimental observations and theoretical analysis

S Nattel

Whereas the interval-dependence of antiarrhythmic drug effects on Vmax is known, the corresponding time-dependence of drug-induced changes in cardiac conduction is not established. The purpose of these experiments was to study the relationship between the time-dependence of lidocaine- induced changes in Vmax and in conduction time. Standard microelectrode techniques were used to monitor conduction and action potential characteristics of Purkinje fibers within free-running canine false tendons. Lidocaine-induced alterations in conduction and Vmax were related to drug concentration and to the preceding diastolic recovery time. At concentrations of 18 to 74 microM, changes in both Vmax and conduction time were an exponential function of diastolic interval, with recovery time constants averaging 123 to 150 msec for conduction time and 138 to 150 msec for Vmax. With higher lidocaine concentrations, changes in Vmax continued to be an exponential function of recovery interval, whereas changes in conduction time consistently deviated from the terminal exponential relationship at short diastolic intervals. These observations are consistent with the predictions of a model based on linear cable theory. Calculations using this model suggest that recovery from moderate drug-induced conduction slowing should proceed with a time course similar to changes in Vmax, whereas recovery from more severe conduction slowing should occur more rapidly than changes in Vmax. These observations suggest that the time dependence of drug effects on conduction in vivo can be analyzed quantitatively in relationship to observations on Vmax in vitro.

Volume 241, Issue 1, pp. 275-281, 04/01/1987
Copyright © 1987 by American Society for Pharmacology and Experimental Therapeutics