The antiarrhythmic action of ischaemic preconditioning in rat hearts does not involve functional Gi proteins

Abstract

Ischaemic preconditioning has been reported to be mediated by inhibitory G (Gi) proteins in rabbits; however, the mechanism of preconditioning in rats appears to differ from that in other species. The aim of this study was to determine whether functional Gi proteins are required for the antiarrhythmic action of preconditioning in rats. Donor rats were randomised to receive pertussis toxin (25 micrograms.kg-1 intravenously) or saline. After 48 h the hearts were isolated and Langendorff perfused with blood from untreated support rats. Cardiac rhythm was recorded continuously. Ischaemia and reperfusion were induced by occluding and releasing a snare around the left coronary artery. Following 10 min of aerobic perfusion hearts were further randomised to: (1) control groups (n = 12 per group) which underwent a further 30 min of aerobic perfusion, or (2) preconditioned groups (n = 12 per group) which were subjected to three cycles of 5 min of ischaemia and 5 min of reperfusion. All hearts subsequently underwent 30 min of regional ischaemia and 10 min of reperfusion during which arrhythmias were quantified. In hearts not pretreated with pertussis toxin, preconditioning limited the severity of ischaemia induced arrhythmias. The incidence of ventricular tachycardia was reduced from 100% to 33% and the mean number of ventricular premature beats from 164(SEM 42) to 23(14) (each p < 0.05). Although pretreatment with pertussis toxin completely abolished the bradycardic response to both acetylcholine and adenosine (indicating functional blockade of Gi proteins), it did not significantly influence the degree of antiarrhythmic protection afforded by preconditioning. In pretreated hearts preconditioning reduced the incidence of ventricular tachycardia from 83% to 33% and the mean number of ventricular premature beats from 267(66) to 62(32) (each p < 0.05). The antiarrhythmic action of preconditioning in isolated blood perfused rat hearts does not require functional Gi proteins.