Electrophysiologic effects of d-sotalol in humans

Sotalol is a beta-adrenergic blocking agent that prolongs the duration of the cardiac action potential in humans, without affecting the upstroke velocity of depolarization. The dextrorotatory isomer, d-sotalol, retains these class III effects, but has little beta-blocking activity in vitro. d-Sotalol has not been studied extensively in humans. The electrocardiographic (ECG) and electrophysiologic effects of d- and d,l-sotalol were therefore assessed in a prospective randomized study of 20 patients. Each patient received either d-sotalol (1, 1.5 or 2 mg/kg body weight) or d,l-sotalol (1 mg/kg) by intravenous infusion. The QT and QTc intervals were prolonged and refractoriness increased in the atrium, atrioventricular (AV) node, His-Purkinje system and right ventricle after both d- and d,l-sotalol. After d-sotalol, the increases in both QT and QTc intervals and in atrial and ventricular effective refractory periods were dose dependent. Highly significant linear correlation was demonstrated between the plasma sotalol level and the change in QT (r = 0.86, p = 0.001) and QTc intervals (r = 0.79, p = 0.002), and between the plasma sotalol level and the effective refractory period of the right atrium (r = 0.75, p = 0.005) and ventricle (r = 0.70, p = 0.025). This study confirms that d-sotalol has effects consistent with class III properties. It demonstrates these effects in humans, and suggests that d-sotalol may prove to be a useful antiarrhythmic agent.

This article has been cited by other articles:

				J. Merot, V. Probst, M. Debailleul, U. Gerlach, N. S. Moise, H. Le Marec, and F. Charpentier Electropharmacological characterization of cardiac repolarization in German shepherd dogs with an inherited syndrome of sudden death: abnormal response to potassium channel blockers J. Am. Coll. Cardiol., September 1, 2000; 36(3): 939 - 947. [Abstract] [Full Text] [PDF]

				K. D Freigang, A. Bauer, R. Becker, J. C Senges, P. Kraft, J. Brachmann, W. Kubler, and W. Schoels Differential effects of d-sotalol on normal and infarcted myocardium: an experimental study using epicardial mapping Cardiovasc Res, July 1, 1997; 35(1): 52 - 59. [Abstract] [Full Text] [PDF]

				S. H. Hohnloser, T. Meinertz, P. Stubbs, H. J.G.M. Crijns, J.-J. Blanc, P. Rizzon, and B. Cheuvart Efficacy and Safety of d-Sotalol, a Pure Class III Antiarrhythmic Compound, in Patients With Symptomatic Complex Ventricular Ectopy : Results of a Multicenter, Randomized, Double-blind, Placebo-Controlled Dose-Finding Study Circulation, September 15, 1995; 92(6): 1517 - 1525. [Abstract] [Full Text]