DIRECT AND AUTONOMICALLY MEDIATED EFFECTS OF ORAL QUINIDINE ON RR QT RELATION AFTER AN ABRUPT INCREASE IN HEART-RATE/

Objectives. This study evaluates the direct and autonomically mediated effects of oral quinidine on ventricular repolarization in humans. Ba ckground. Interactions between quinidine-related vagolytic properties and autonomic modulation on ventricular repolarization are unknown. Th e relative role of the two components, if present, might improve our u nderstanding of the therapeutic and proarrhythmic mechanisms of quinid ine on the ventricular tissue.Methods. Rate-related changes in the QT interval were investigated after an abrupt increase in heart rate in 1 5 patients during atrial pacing. In the control study, the QT interval was measured at six paced cycle lengths (600, 540, 500, 460, 430 and 400 ms) both in the basal state and after autonomic blockade (intraven ous propranolol, 0.2 mg/kg, and intravenous atropine, 0.04 mg/kg); ora l quinidine was then administered at a daily dosage of 1,200 mg for 3 to 4 days, after which the QT duration was reassessed using the same m ethod in a second study. Results. During the control study, the mean s lope of the regression curve estimating the correlation between pacing cycle length and QT duration was significantly lower after autonomic blockade (0.14 +/- 0.05) than in the basal state (0.27 +/- 0.10, p < 0 .05). Quinidine exhibited a prominent but opposite effect on the mean slope of the regression curves in basal conditions (from 0.27 +/- 0.10 to 0.20 +/- 0.07, p < 0.05) and after withdrawal of autonomic modulat ion (from 0.14 +/- 0.05 to 0.19 +/- 0.05, p < 0.05), thus annulling th e differences observed between the two states in the control study. Co nclusions. A quinidine-induced increase in QT duration as cycle length is prolonged is consistent with a reverse use dependence effect on ve ntricular repolarization. This effect is not evident in the basal stat e owing to interaction of quinidine-related vagolytic effect with the autonomic tone. Reverse use dependence and vagolytic activity on ventr icular tissue indicate two potentially undesirable effects that could play a role in the lack of efficacy or proarrhythmic effect of quinidi ne.