Kinetics of Frequency-Dependent Conduction Delay by Class I Antiarrhythmic Drugs in Human Atrium

Abstract

We investigated use-dependent prolongation of interatrial conduction time (IACT) by class I antiarrhythmic drugs in 16 patients. Changes in IACT at the initiation of atrial pacing were used to evaluate the onset kinetics. We examined recovery kinetics by giving a single extra stimulus with a varying coupling interval after discontinuing train stimulation. Time constants of the onset kinetics were 1.52 +/- 0.15/n(fast) and 0.087 +/- 0.031/n(slow) for mexiletine, 0.075 +/- 0.015/n for aprindine, 0.078 +/- 0.019/n for disopyramide, and 0.050 +/- 0.006/n for pilsicainide. The recovery time constants were 203 +/- 66 ms for mexiletine, 1,021 +/- 162 ms for aprindine, 993 +/- 101 ms for disopyramide, and 2,930 +/- 569 ms for pilsicainide. Class I antiarrhythmic drugs produced use-dependent IACT prolongation in humans, with characteristic kinetics for each agent similar to that of depression of the maximum upstroke velocity of cardiac action potential (Vmax) reported in in vitro studies.