Sarafotoxin 6c Protects Against IschaemiaInduced Cardiac Arrhythmias In Vivo and In Vitro in the Rat

The aim of this study was to investigate whether the endothelinB ETBreceptor agonist sarafotoxin 6c S6c can protect against ischaemiainduced cardiac arrhythmias. Arrhythmias were induced by a 30 min period of coronary artery occlusion in pentobarbitoneanaesthetized male rats, or in Langendorffperfused rat hearts. Rats or rat hearts were administered a bolus dose of vehicle or S6c 0.8 nmolkg i.v. or 10-8M 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 ETBreceptors, 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.