The aim of this study was to investigate whether the endothelin-B- (ETB) receptor agonist sarafotoxin 6c (S6c) can protect against ischaemia-induced cardiac arrhythmias. Arrhythmias were induced by a 30 min period of coronary artery occlusion in pentobarbitone-anaesthetized male rats, or in Langendorff-perfused rat hearts. Rats or rat hearts were administered a bolus dose of vehicle or S6c (0.8 nmol/kg i.v. or 10−8 M into the coronary circulation, respectively) 5 min before the onset of ischaemia. In vivo administration of S6c significantly reduced the incidence of ventricular fibrillation (VF) from 59% to 13% and the number of premature ventricular beats. This effect was associated with a transient fall in mean arterial blood pressure. In isolated hearts, S6c reduced significantly both the incidences of ventricular tachycardia (VT) and VF while having no statistically significant effect on coronary perfusion pressure. This is the first report to show that stimulation of ETB-receptors, with a bolus dose of S6c, has an antiarrhythmic effect on rat hearts both in vivo and in vitro, suggestive of a direct effect on the myocardium.
Department of Physiology & Pharmacology, University of Strathclyde, Glasgow, Scotland, U.K.
Address correspondence and reprint requests to Dr Cherry L. Wainwright, Department of Physiology & Pharmacology, University of Strathclyde, SIBS, 27 Taylor Street, Glasgow G4 0NR, Scotland, U.K. E-mail: [email protected]
© 2000 Lippincott Williams & Wilkins, Inc.