Frequency-dependent effects of antiarrhythmic drugs on action potential duration and refractoriness of canine cardiac Purkinje fibers.

Abstract

Antiarrhythmic drugs are known to have frequency dependent effects on Vmax and conduction. The purpose of this study was to determine whether the effects of antiarrhythmic drugs on action potential duration (APD) and refractory period depend on frequency. Standard microelectrode techniques were used to measure APD and refractory period after abrupt or sustained alterations in stimulation frequency. Increases in APD95 resulting from bretylium and quinidine and decreases resulting from lidocaine were 50 to 60% attenuated (P less than .01 for each) by sustained increases in activation rate. Unlike sustained rate increases, abrupt increases in rate enhanced quinidine-induced APD prolongation (P less than .01). Quinidine increased the time constant (222 +/- 6 to 346 +/- 36 msec, P less than .01) and decreased the magnitude of the rapid phase of APD abbreviation upon premature stimulation. In contrast, bretylium increased the magnitude of APD abbreviation upon premature stimulation, reducing the tendency of bretylium to prolong premature APD compared to basic APD. Changes in refractory period parallelled changes in APD95 with the exception of the effect of quinidine after sustained rate change. Despite attenuation of its effects oN APD95, quinidine prolonged refractory period more after sustained rate increases (P less than .01), apparently because of greater depression of maximum sodium conductance. These experiments show that the effects of antiarrhythmic drugs on APD and refractoriness depend on activation frequency and that abrupt changes in rate may alter drug effects differently from sustained rate changes.