Author + information
- Received May 24, 1985
- Revision received August 20, 1985
- Accepted September 3, 1985
- Published online January 1, 1986.
- Rinya Kato, MD,
- Nobuo Ikeda, MD,
- Steven M. Yabek, MD, FACC*,
- Ramaswamy Kannan, PhD and
- Bramah N. Singh, MD, DPhil, FACCa
- ↵aAddress for reprints: Bramah N. Singh, MD, Cardiology Section, 691/111E, Wadsworth Veterans Administration Hospital, Wilshire/ Sawtelle Boulevards, Los Angeles, California 90073.
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 μg/ml), d- and l-sotalol prolonged APD90(by 38 and $4%, 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 μg/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.
↵* Department of Pediatrics, University of New Mexico, School of Medicine, Albuquerque, New Mexico.
This study was supported in part by grants from the Medical Research Service of Veterans Administration, Washington, D.C., and by the American Heart Association Greater Los Angeles Affiliate, Los Angeles, California.
- Received May 24, 1985.
- Revision received August 20, 1985.
- Accepted September 3, 1985.
- American College of Cardiology Foundation