Differences in the Effects of d- and dl-Sotalol on Isolated Human Ventricular Muscle: Electromechanical Activity After Beta-Adrenoceptor Stimulation

Abstract

Background: The racemate of sotalol (dl-sotalol) and its dextrorotatory isomer ( d-sotalol) are equally effective in increasing isolated cardiac action potential durations. dl-Sotalol, however, is reported to be more effective than d-sotalol in increasing ventricular effective refractoriness following coronary artery occlusion. These differences are attributed to the beta-adrenergic blocking properties of dl-sotalol. We wished to determine if in isolated human ventricular muscle preparations the effects of 30 μM d- and dl-sotalol could be modified by preexposure to 1 μM isoproterenol.

Methods and Results: Microelectrodes were used to record action potential duration (APD) in the presence and absence of isoproterenol during continuous pacing. Preparations were obtained from explanted hearts of transplant recipients suffering idiopathic cardiomyopathies. Without isoproterenol, APD measured at 90% of repolarization (APD₉₀) was signiticantly increased by both d- and dl-sotalol (352.0 ± 17.7 to 418.0 ± 23.8 ms, P < .05; and 339.2 ± 17.0 to 405.0 ± 25.3 ms, P < .05; respectively). Isoproterenol alone, prior to sotalol exposure, tended to shorten APD₉₀ in the two groups first exposed to this beta-aclenoceptor agonist and subsequently exposed to either d-sotalol or dl-sotalol (317.5 ± 16.5 to 286.2 ± 28.8 ms and 288.0 ± 16.2 to 254.0 ± 15.0 ms, respectively). dl-Sotalol signiticantly increased APD₉₀ from its baseline value after isoproterenol (288.0 ± 16.2 to 359.0 ± 25.1 ms, P < .005) while d-sotalol did not (317.5 ± 16.5 to 316.2 ± 28.5 ms, NS).

Conclusions: The beta-adrenergic blocking properties of dl-sotalol may be important in determining antiarrhythmic efficacy when tonic sympathetic nervous activity is high.