The Effect of Rate on Prolongation of Ventricular Refractoriness by Quinidine in Humans

In this study, the rate dependent effect of quinidine on the ventricular elective refractory period (VERP) was evaluated in 30 patients undergoing electropharmacological testing with quinidine. The VERPs were measured in the baseline state and after at least 2 days of treatment with 1,458–2,044 mg/day of quinidine gluconate (mean plasma quinidine concentration 2.2 ± 0.7 mcg/mL). In 20 patients, the VERP was measured using conventional basic drive trains of 8 beats and basic drive cycle lengths of 600, 500, 400, and 350 msec. In another 10 patients, the VERP was measured after 3 minutes of continuous ventricular pacing at cycle lengths of 600 and 400 msec, and compared to the VERPs measured at the same basic drive cycle lengths using basic drive train durations of 2 and 8 beats. In the baseline state and after treatment with quinidine, the VERP shortened progressively as the basic drive train cycle length decreased and as the drive train duration increased to 3 minutes (P < 0.001). Quinidine consistently prolonged the VERP by 9%–11% (P < 0.001 J, regardless of the basic drive train cycle length. Quinidine's effect was also not affected by the basic drive train duration. In conclusion, the effect of quinidine on VERP in humans is independent of the rate of the basic drive train, both when measured using conventional 8‐beat basic drive trains and when a three minute drive train duration is used in order to attain the maximum effect of the basic drive train cycle length on the VERP. Therefore, in contrast to quinidine's known rate dependent effect on conduction, it's effect on ventricular refractoriness at doses and basic drive train cycle lengths which are used clinically are not rate dependent.