Sarafotoxin 6c protects against ischaemia-induced cardiac arrhythmias in vivo and in vitro in the rat

The aim of this study was to investigate whether the endothclin-B- (ETB) re ceptor agonist sarafotoxin 6c (S6c) can protect against ischaemia-induced c ardiac arrhythmias. Arrhythmias were induced by a 30 min period of coronary artery occlusion in pentobarbitone-anaesthetized male rats, or in Langendo rff-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 circulati on, respectively) 5 min before the onset of ischaemia. In vivo administrati on of S6c significantly reduced the incidence of ventricular fibrillation ( VF) from 59% to 13% and the number of premature ventricular heats. This eff ect was associated with a transient fall in mean arterial blood pressure. I n isolated hearts, S6c reduced significantly both the incidences of ventric ular tachycardia (VT) and VF while having no statistically significant effe ct on coronary perfusion pressure. This is the first report to show that st imulation 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 eff ect on the myocardium.