Electrophysiologic effects of the levo- and dextrorotatory isomers of sotalol in isolated cardiac muscle and their in vivo pharmacokinetics

Dl-sotalol is a specific beta-adrenergic blocking agent that markedly lengthens cardiac action potential duration. To determine whether d-sotalol, with little or no beta-blocking effect, also lengthens repolarization, standard microelectrode studies were used to determine the electrophysiologic properties of dl-sotalol and its stereoisomers in isolated rabbit and canine myocardial fibers. D- and l-sotalol produced concentration-dependent increases in action potential duration to 50% (APD50) and 90% (APD90) repolarization, respectively, and in the effective refractory period without changes in the maximal rate of rise of action potential. In rabbit sinoatrial node, d- and l-sotalol produced concentration-dependent increases in spontaneous sinus cycle length (29 and 35%, respectively) by lengthening the action potential duration (by 58 and 55%) without effect on phase 4 depolarization. At the highest concentration (27.2 micrograms/ml), d- and l-sotalol prolonged APD90 (by 38 and 54%, respectively, in Purkinje fibers and by 32 and 34% in ventricular muscle) and effective refractory period (by 49 and 49% in Purkinje fibers and 29 and 40% in ventricular muscle). The effects of the two isomers were not significantly different. At the middle concentration (2.7 micrograms/ml), d-sotalol, unlike l-sotalol, had no beta-adrenergic blocking effect, but the electrophysiologic effects of dl-, d- and l-sotalol were indistinguishable. The data indicate that d-sotalol is equipotent with l-sotalol in lengthening the action potential duration and effective refractory period in cardiac muscle, an action unrelated to adrenergic antagonism or pharmacokinetic differences between the stereoisomers.

This article has been cited by other articles:

				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. Sicouri, S. Moro, and M. V. Elizari d-Sotalol Induces Marked Action Potential Prolongation and Early Afterdepolarizations in M but Not Epicardial or Endocardial Cells of the Canine Ventricle Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(1): 27 - 37. [Abstract] [PDF]

				P. C. Deedwania Sotalol Is More Powerful Than Propranolol in Suppressing Complex Ventricular Arrhythmias Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1997; 2(4): 259 - 272. [Abstract] [PDF]

				D. A. Lathrop, A. Varro, P. P. Nanasi, I. Bodi, E. Takyi, and C. Pankucsi Differences in the Effects of d- and dl-Sotalol on Isolated Human Ventricular Muscle: Electromechanical Activity After Beta-Adrenoceptor Stimulation Journal of Cardiovascular Pharmacology and Therapeutics, January 1, 1996; 1(1): 65 - 73. [Abstract] [PDF]

				C. Holubarsch, R. Schneider, B. Pieske, T. Ruf, G. Hasenfuss, G. Fraedrich, H. Posival, and H. Just Positive and Negative Inotropic Effects of DL-Sotalol and D-Sotalol in Failing and Nonfailing Human Myocardium Under Physiological Experimental Conditions Circulation, November 15, 1995; 92(10): 2904 - 2910. [Abstract] [Full Text]

				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]

				W. J. Groh, K. J. Gibson, J. H. McAnulty, and J. G. Maylie -Adrenergic Blocking Property of dl-Sotalol Maintains Class III Efficacy in Guinea Pig Ventricular Muscle After Isoproterenol Circulation, January 15, 1995; 91(2): 262 - 264. [Abstract] [Full Text]