Protective effects of preconditioning of the ischaemic myocardium involve cyclo-oxygenase products

Abstract

Study objective – The aim was to determine whether short (preconditioning) occlusions of a coronary artery protect against the arrhythmias occurring during a subsequent more prolonged occlusion and to examine whether the observed protection is mediated by the release of a product of the cyclo-oxygenase pathway of arachidonic acid metabolism. Design – The effects were examined of two short (5 min) coronary artery occlusions, in chloraloseurethane anaesthetised dogs, on a subsequent prolonged (25 min) occlusion; analysis of ischaemia and reperfusion induced arrhythmias and of epicardial ST segment changes was performed. Experimental material – 46 anaesthetised mongrel dogs in a restricted body weight range were used. Measurements and main results – Preconditioning reduced the incidence and severity of ischaemic arrhythmias during a 25 min occlusion. Ventricular premature beats (VPB) reduced from 445 (SEM 140) to 96(22) (p<0.0l), ventricular fibrillation (VF) from 4/10 to 0/20 (p<0.05), and ventricular tachycardia from 9/10 to 6/20 (p<0.05). VF following reperfusion was reduced from 6/6 to 6/10 (p<0.05). Preconditioning thus increased survival from the prolonged ischaemia-reperfusion insult from 0% to 40%. The protective effect of preconditioning was lost in the presence of the cyclo-oxygenase inhibitor sodium meclofenamate (2 mg·kg−1), eg, VPBs 367(95), VF during occlusion 1/9 and during reperfusion 8/8, survival 0%. Conclusions – Short, preconditioning periods of myocardial ischaemia protect the myocardium against the arrhythmogenic effects of a more prolonged occlusion. That this protection is lost if the cyclo-oxygenase pathway is blocked suggests a protective role for prostanoids, most likely prostacyclin, as endogenous myocardial protective substances.