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(Circulation. 1995;91:262-264.)
© 1995 American Heart Association, Inc.

Articles

ß-Adrenergic Blocking Property of dl-Sotalol Maintains Class III Efficacy in Guinea Pig Ventricular Muscle After Isoproterenol

Presented in part at the Annual Meeting of the North American Society of Pacing and Electrophysiology, Nashville, Tenn, May 11-14, 1994.

William J. Groh, MD; Kevin J. Gibson, BA; John H. McAnulty, MD; James G. Maylie, PhD

From the Division of Cardiology, Department of Medicine (W.J.G., J.H.M.) and the Department of Obstetrics and Gynecology (K.J.G., J.G.M.), Oregon Health Sciences University, Portland.

Correspondence to James G. Maylie, PhD, Oregon Health Sciences University M/S L468, 3181 SW Sam Jackson Park Rd, Portland, OR 97201-3098.

Background Catecholamines antagonize the efficacy of several class III antiarrhythmic agents. To determine the role of the intrinsic ß-adrenergic blocking property of dl-sotalol in maintaining class III efficacy during a high-catecholamine state, we compared the electrophysiological properties of dl-sotalol with those of d-sotalol, which is devoid of significant ß-adrenergic blocking effect, before and after isoproterenol infusion.

Methods and Results Action potential duration at 90% repolarization (APD₉₀) was prolonged in isolated guinea pig papillary muscles perfused with d-sotalol and dl-sotalol 10^-4 mol/L over stimulation cycle lengths from 200 to 2000 ms. The increases in APD₉₀ for d-sotalol and dl-sotalol over control were 10.9±2.5 to 23.7±4.8 ms and 27.9±4.0 to 39.0±5.6 ms, respectively. APD₉₀ shortened to less than control in papillary muscles treated with d-sotalol but not dl-sotalol on addition of isoproterenol 10^-6 mol/L: -31.2±3.5 to -18.3±4.8 ms and 10.5±3.6 to 33.3±7.8 ms, respectively, P<.003. Single guinea pig ventricular myocytes were studied by the whole-cell patch clamp method. Time-dependent (I_out) and total (I_tot) outward current in response to a 300-ms pulse to 20 mV and tail current (I_tail) to -35 mV were measured after Ca²⁺ channel block and Na⁺ channel inactivation. I_out, I_tail, and I_tot were reduced in myocytes perfused with d-sotalol and dl-sotalol 10^-4 mol/L: I_out, -36.1±4.1%, -40.5±3.3%; I_tail, -59.3±4.6%, -62.2±11.1%; I_tot, -27.3±4.3%, -50.0±11.8%. I_out and I_tot increased to a greater degree in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol 10^-6 mol/L: I_out, 100.3±20.6%, 11.3±7.6%, P=.002; I_tot, 86.8±39.2%, -41.1±20.9%, P=.01. I_tail tended to increase more in myocytes treated with d-sotalol than dl-sotalol on addition of isoproterenol, but the difference was not significant (-9.1±13.5%, -28.0±9.0%).

Conclusions The ß-adrenergic blocking property of dl-sotalol maintains APD prolongation and repolarizing outward current block during isoproterenol infusion in guinea pig ventricular muscle. Extrapolation of these data to a clinical setting may explain the efficacy of dl-sotalol in diminishing ventricular arrhythmia recurrence.

Key Words: antiarrhythmia agents • potassium • catecholamines

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