A Vegh1, L Szekeres, J R Parratt. 1. Institute of Pharmacology, Albert Szent-Gyorgyi Medical University, Szeged, Hungary.
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 chloralose-urethane 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 less than 0.01), ventricular fibrillation (VF) from 4/10 to 0/20 (p less than 0.05), and ventricular tachycardia from 9/10 to 6/20 (p less than 0.05). VF following reperfusion was reduced from 6/6 to 6/10 (p less than 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.
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 chloralose-urethane 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 less than 0.01), ventricular fibrillation (VF) from 4/10 to 0/20 (p less than 0.05), and ventricular tachycardia from 9/10 to 6/20 (p less than 0.05). VF following reperfusion was reduced from 6/6 to 6/10 (p less than 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.
Authors: E K Iliodromitis; C Papadopoulos; I A Paraskevaidis; Z S Kyriakides; C Flessa; D T Kremastinos Journal: Cardiovasc Drugs Ther Date: 1996-07 Impact factor: 3.727