Pharmacologic basis of the antiarrhythmic and hemodynamic effects of sotalol

• Published in: The American journal of cardiology Vol. 72; no. 4; pp. A27 - A37
• Main Authors: Antonaccio, Michael J., Gomoll, Allen
• Format: Journal Article Conference Proceeding
• Language: English
• Published: New York, NY Elsevier Inc 12.08.1993; Elsevier; Elsevier Limited
• Subjects: Action Potentials - drug effects; Animals; Anti-Arrhythmia Agents - pharmacology; Antiarythmic agents; Biological and medical sciences; Cardiac arrhythmia; Cardiovascular system; Dose-Response Relationship, Drug; Heart - drug effects; Heart - physiology; Hemodynamics - drug effects; Humans; Medical research; Medical sciences; Myocardial Contraction - drug effects; Pharmacology; Pharmacology. Drug treatments; Prescription drugs; Sotalol - pharmacology; In vivo; Hemodynamics; In vitro; Biological activity; Antiarrhythmia agent; Beta blocking agent
• ISSN: 0002-9149; 1879-1913
• DOI: 10.1016/0002-9149(93)90022-5

Sotalol is a competitive β adrenoceptor antagonist devoid of membrane-stabilizing activity and intrinsic sympathomimetic activity that has no preferential actions on β 1 or β 2 responses. No other tested receptor systems are affected by sotalol. In addition to having class II (β blockade) effects, sotalol also has class III antiarrhythmic activity. It increases the action potential duration (APD) and prolongs atrial and ventricular repolarization. The effect on APD is independent of β blockade; the same effect is seen with similar concentrations of the d stereoisomer of sotalol, which does not have β-blocking activity. Sotalol prolongs the rate-corrected QT interval and ventricular and atrial refractoriness without affecting atrial, His-Purkinje, or ventricular conduction velocity. Atrioventricular nodal conduction is decreased, largely because of β blockade. Sotalol increases the fibrillation threshold and decreases the defibrillation threshold. Sotalol is an effective antiarrhythmic in various animal models of arrhythmia (e.g., chloroform, hydrocarbon—catecholamine, ouabain, and coronary ligation). In addition, it reduces the severity and frequency of arrhythmias induced by programmed electrical simulation. By comparison, metoprolol is ineffective and d-sotalol is as effective as the racemate in this model, indicating that this effect is independent of β blockade. Sotalol causes concentration-dependent increases in the contractility of isolated ventricular tissue that is not blocked by previous β or α blockade or catecholamine depletion. The positive inotropic effect may be related to inhibition of time-dependent K + current responsible for the increase in APD. Like propranolol, sotalol decreases contractile force, heart rate, arterial blood pressure, left ventricular dP dt , and cardiac output in intact animals due to blockade of circulating catecholamines. Sotalol consistently reduces the heart rate to a greater degree than propranolol and causes significantly less cardiac suppression than propranolol at a given heart rate.