FREQUENCY-DEPENDENT ELECTROPHYSIOLOGIC EFFECTS OF D,L-SOTALOL AND QUINIDINE AND MODULATION BY BETA-ADRENERGIC STIMULATION

Introduction: Frequency-dependent electrophysiologic actions of oral q uinidine and oral sotalol may be clinically important, but these prope rties and their modulation by beta-adrenergic sympathetic stimulation have not been determined. Methods and Results: The frequency-dependent effects of oral quinidine (n = 17) and oral d,l-sotalol (n = 17) were determined at: (1) drug-free baseline; (2) during steady-state drug d osing; and (3) during isoproterenol infusion to patients receiving qui nidine or d,l-sotalol. The monophasic APD(90) and RVERP were prolonged 12% to 17% (P < 0.001) during pharmacologic therapy, and frequency-de pendent effects were only observed for the RVERP during sotalol. In bo th drug groups, isoproterenol significantly reduced the sinus cycle le ngth and reduced the RVERP to a greater extent at longer than at short er paced cycle lengths. While isoproterenol fully reversed quinidine's effects on the APD(90) and RVERP, sotalol-induced APD(90) prolongatio n was reduced by only 2% to 4%, and the RVERP was unaffected. Isoprote renol attenuated the frequency-dependent effects of quinidine on QRS d uration by a relatively fixed amount of 7% to 10%. Isoproterenol fully reversed quinidine-induced, but did not affect sotalol-induced, prolo ngation in the sustained VT cycle length. Conclusions: (1) Over the ra nge of examined cycle lengths, oral quinidine and d,l-sotalol did not exert frequency-dependent effects on ventricular repolarization. (2) I soproterenol fully reversed quinidine's effects on refractoriness, rep olarization, and prolongation of VT cycle length, whereas d,l-sotalol' s effects were largely preserved, despite significant reductions in si nus cycle length. (3) These results suggest that beta-blockade is impo rtant in preventing reversal of antiarrhythmic drug effects by augment ed sympathetic nervous system tone.