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


METHODS
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.


METHODS
46 anaesthetised mongrel dogs in a restricted body weight range were used.


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.
Vegh
A
A
Institute of Pharmacology, Albert Szent-Gyorgyi Medical University, Szeged, Hungary.
Szekeres
L
L
Parratt
J R
JR
D000818:Animals; D003327:Coronary Disease / Q000201:enzymology* / Q000503:physiopathology; D016861:Cyclooxygenase Inhibitors; D004285:Dogs; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000502:physiology*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D015425:Myocardial Reperfusion; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013997:Time Factors
D016861:Cyclooxygenase Inhibitors; D008469:Meclofenamic Acid; D011451:Prostaglandin-Endoperoxide Synthases