FREQUENCY-DEPENDENT EFFECTS OF ANTIARRHYTHMIC DRUGS ON ACTION-POTENTIAL DURATION AND REFRACTORINESS OF CANINE CARDIAC PURKINJE-FIBERS

  • 1 January 1984
    • journal article
    • research article
    • Vol. 229  (1) , 283-291
Abstract
Antiarrhythmic drugs have frequency dependent effects on .ovrhdot.Vmax and conduction. Whether the effects of antiarrhythmic drugs on action potential duration (APD) and refractory period depend on frequency was determined. Standard microelectrode techniques were used to measure APD and refractory period after abrupt or sustained alterations in stimulation frequency. Increases in APD95 [to 95% repolarization] resulting from bretylium and quinidine and decreases resulting from lidocaine were 50-60% attenuated (P < 0.01 for each) by sustained increases in activation rate. Unlike sustained rate increases, abrupt increases in rate enhanced quinidine-induced APD prolongation (P < 0.01). Quinidine increased the time constant (222 .+-. 6 to 346 .+-. 36 ms, P < 0.01) and decreased the magnitude of the rapid phase of APD abbreviation upon premature stimulation. 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 paralleled changes in APD95 with the exception of the effect of quinidine after sustained rate change. Despite attenuation of its effects on APD95, quindidine prolonged refractory period more after sustained rate increases (P < 0.01), apparently because of greater depression of maximum Na conductance. The effects of antiarrhythmic drugs on APD and refractoriness evidently depend on activation frequency and abrupt changes in rate may alter drug effects differently from sustained rate changes.

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