Free radicals and myocardial ischemia. The role of xanthine oxidase.
Recent studies have established a major role for oxygen-derived free radicals in post ischemic tissue injury to the intestine. During ischemia, there appears to be a calcium-triggered, protease-dependent conversion of the native xanthine dehydrogenase to a superoxide-producing xanthine oxidase. The catabolic degradation of ATP during ischemia provides an oxidizable substrate, hypoxanthine. On reperfusion, molecular oxygen is resupplied and a burst of superoxide production ensues, resulting in extensive tissue damage. The same mechanism appears to occur in myocardial ischemia. Xanthine dehydrogenase rapidly converts to the oxidase during nonperfusion in the rat heart. In the isolated perfused working rat heart model, 40 min of anoxia followed by reoxygenation results in substantial release of creatine kinase. The release of creatine kinase is blocked almost completely by pretreatment of the rats with allopurinol, a specific inhibitor of xanthine oxidase.
McCord
J M
JM
Roy
R S
RS
Schaffer
S W
SW
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D003327:Coronary Disease / Q000201:enzymology / Q000378:metabolism*; D003402:Creatine Kinase / Q000378:metabolism; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D007422:Intestines / Q000201:enzymology; D007658:Ketone Oxidoreductases / Q000378:metabolism*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013481:Superoxides / Q000378:metabolism*; D014968:Xanthine Dehydrogenase / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D005609:Free Radicals; D013481:Superoxides; D000493:Allopurinol; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D007658:Ketone Oxidoreductases; D003402:Creatine Kinase