FREQUENCY-DEPENDENT EFFECTS OF QUINIDINE ON THE VENTRICULAR ACTION-POTENTIAL AND QRS DURATION IN HUMANS

We studied the frequency-dependent effects of quinidine on the right ventricular action potential and QRS duration in 10 patients (nine men and one woman; mean age, 57±14 years) undergoing electrophysiologic studies for clinical indications. The right ventricular monophasic action potential, electrocardiographic, and conventional intracardiac electrical signals from various sites were recorded at different pacing cycle lengths from 30 seconds to 1 minute before and after a 10-mg/kg i.v. quinidine infusion. We used the extrastimulus technique to determine the effects of quinidine on ventricular refractory periods at different pacing cycle lengths and on the abrupt changes of the action potential duration. The action potential duration progressively decreased as the ventricular pacing rate increased at baseline and after quinidine infusion. Quinidine significantly increased the action potential duration from that of control by 25 msec (p<0.02) at the relatively slow pacing cycle lengths of 600, 500, and 400 msec. Quinidine's effect on the action potential duration was attenuated at the pacing cycle length of 350 msec and became negligible at 300 msec. In contrast, quinidine progressively lengthened the QRS duration as the pacing rate increased (20, 18, 37, 46, and 34 msec at pacing cycle lengths of 600, 500, 400, 350, and 300 msec, respectively; p<0.05). There were no rate-dependent changes in the QRS duration during the control period. The relation between the ventricular refractory periods and the action potential duration at different pacing cycle lengths was also determined before and after quinidine infusion. Quinidine uniformly increased the ventricular refractory periods by about 9-11% above the control values regardless of the pacing cycle lengths and the action potential durations. Although quinidine generally had no effect on the ratio of ventricular effective refractory period to the action potential duration, a strong trend emerged showing that quinidine increased the ratio as the pacing cycle lengths shortened (p=0.07). Our data demonstrate that at slower heart rates quinidine has a significant effect on the action potential duration, repolarization, and voltage-dependent refractory period. As the heart rate increased, quinidine's effect on these variables diminished, but its effect on the time-dependent refractory period became more pronounced. In contrast to quinidine's effect on the action potential duration, the drug prolonged the QRS duration in a use-dependent manner.