Action of sotalol on potential reentrant pathways and ventricular tachyarrhythmias in conscious dogs in the late postmyocardial infarction phase.

Abstract

Sotalol is a ,3-adrenergic blocker that also prolongs action potential duration and myocardial refractoriness over the short term (class III effect). Its short-term antiarrhythmic effects were compared with those of metoprolol, which has neither short-term class III nor membranestabilizing action, on reentrant ventricular arrhythmias produced by programmed stimulation in 17 conscious dogs 3 to 8 days after myocardial infarction. Ventricular arrhythmias were prevented or significantly slowed by sotalol in 11 of 19 studies (58%) compared with in one of 14 (7%) studies with metoprolol. Sotalol prolonged refractoriness in the infarct zone, measured from an implanted "composite" electrode, by 41 45% (mean ± SD, p < .01), which was significantly greater than the increases it produced in effective refractory period of the normal ventricle (14.0 + 5.5%) or QT interval (12.5 ± 7.8%). Metoprolol had no effect on infarct-zone refractoriness. Sotalol differentially increases refractoriness in potential reentry circuits in ischemic myocardium. Its antiarrhythmic effect in this model is not due to /8-blockade, and is presumably related to prolongation of action potential duration. Circulation 68, No. 4, 865-871, 1983. SOTALOL is unique among currently available 38-adrenergic blockers in that it produces short-term prolongation of myocardial action potential duration and effective refractory period (ERP) in vitro. According to Vaughan-Williams' classification,3 therefore, sotalol has class III as well as class II antiarrhythmic properties. It has recently been shown that sotalol prolongs monophasic action potential duration in man,4'5 and produces acute increases in the ERPs of human atria, ventricles, and atrioventricular accessory pathways.6 7The purpose of this study was to examine the shortterm effects of sotalol on reentrant ventricular arrhythmias and epicardial infarct-zone potentials in experimental canine myocardial infarction.8 9 The effects of sotalol were compared with those of metoprolol, a cardioselective /3-adrenergic blocker that is devoid of short-term class III

Developmental Cellular Electrophysiologic Effects of d-Sotalol on Canine Cardiac Purkinje Fibers

“…Before this study, Cobbe el al. (32) studied the electrophysiologic actions of sotalol in a conscious canine model of myocardial infarction. These investigators found a significant increase in ischemic zone refractoriness, the mechanism of which could not be explained.…”

Ventricular Repolarization Time - Effect of Chronic Beta Blockade with Class II and/or Class III Properties

“…A quantitative difference thus exist be tween sotalol and metoprolol regarding the class Ill-like mode of action after long-term therapy. A qualitative difference was indicated by a previous report in which sotalol, in contrast to metoprolol, significantly prolonged ventricular refractoriness in infarcted zones compared to normal myocardium after acute administration in dogs [16]. Moreover, sotalol significantly prevented and slowed ventricular arrhythmias in ischemic myocar dium, an effect that could not be demonstrated after metoprolol treatment.…”

Day-to-day variations in inducibility of ventricular tachyarrhythmias during the late postmyocardial infarction phase in conscious dogs.

“…6 The surgical technique of two-stage proximal ligation of the left anterior descending coronary7 and implantation of atrial and ventricular bipolar stimulating electrodes and subcutaneous electrocardiographic electrodes has recently been described in detail. 8 Fifteen dogs were studied with programmed stimulation over 3 to 8 days after infarction. They had been trained to stand unsedated in a sling.…”