Free Radicals and Myocardial Ischemia
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- de pen dent 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.
KeywordsCreatine Kinase Xanthine Oxidase Xanthine Dehydrogenase Superoxide Free Radical Enzyme Xanthine Oxidase
Unable to display preview. Download preview PDF.
- 9.Roy, R. S., and McCord, J. M. 1983. Superoxide and ischemia: Conversion of xanthine dehydrogenase to xanthine oxidase. In: R. A. Greenwald and G. Cohen (eds.), Oxy Radicals and Their Scavenger Systems. Volume II. Cellular and Medical Aspects. pp. 145–153. Elsevier Science, New York.Google Scholar
- 11.Krenitsky, T. A., Tuttle, J. V., Cattau, E. L., Jr., and Wang, P. 1974. A comparison of the distribution and electron acceptor specificities of xanthine oxidase and aldehyde oxidase. Comp. Biochem. Physiol. 49B:687–703.Google Scholar
- 16.Grøgaard, B., Parks, D. A., Granger, D. N., McCord, J. M., and Forsberg, J. 1982. Effects of ischemia and superoxide radicals on mucosal albumin clearance in the dog intestine. Am. J. Physiol. 5:448–454.Google Scholar