Free Radicals and Myocardial Ischemia

The Role of Xanthine Oxidase
  • Joe M. McCord
  • Ranjan S. Roy
  • Stephen W. Schaffer
Part of the Advances in Myocardiology book series (ADMY)


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.


Creatine Kinase Xanthine Oxidase Xanthine Dehydrogenase Superoxide Free Radical Enzyme Xanthine Oxidase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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  1. 1.
    McCord, J. M., and Fridovich, I. 1968. The reduction of cytochrome c by milk xanthine oxidase. J. Biol. Chem. 243:5753–5760.PubMedGoogle Scholar
  2. 2.
    McCord, J. M., and Fridovich, I. 1978. The biology and pathology of oxygen radicals. Ann. Intern. Med. 89:122–127.PubMedCrossRefGoogle Scholar
  3. 3.
    Petrone, W. F., English, D. K., Wong, K., and McCord, J. M. 1980. Free radicals and inflammation: Superoxide-dependent activation of a neutrophil chemotactic factor in plasma. Proc. Natl. Acad. Sci. U.S.A. 77:1159–1163.PubMedCrossRefGoogle Scholar
  4. 4.
    Granger, D. N., Rutili, G., and McCord, J. M. 1981. Superoxide radicals in feline intestinal ischemia. Gastroenterology 81:22–29.PubMedGoogle Scholar
  5. 5.
    Parks, D. A., Bulkley, G. B., Granger, D. N., Hamilton, S. R., and McCord, J. M. 1982. Ischemic injury in the cat small intestine: Role of superoxide radicals. Gastroenterology 82:9–15.PubMedGoogle Scholar
  6. 6.
    Battelli, M. G., Della Corte, E., and Stirpe, F. 1972. Xanthine oxidase type D (dehydrogenase) in the intestine and other organs of the rat. Biochem. J. 126:747–749.PubMedGoogle Scholar
  7. 7.
    Stirpe, F., and Della Corte, E. 1969. The regulation of rat liver xanthine oxidase: Conversion in vitro of the enzyme activity from dehydrogenase (type D) to oxidase (Type O). J. Biol. Chem. 244:3855–3863.PubMedGoogle Scholar
  8. 8.
    McCord, J. M., and Roy, R. S. 1982. The pathophysiology of superoxide: Roles in inflammation and ischemia. Can. J. Physiol. Pharmacol. 60:1346–1352.PubMedCrossRefGoogle Scholar
  9. 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
  10. 10.
    Jones, C. E., Crowell, J. W., and Smith, E. E. 1968. Significance of increased blood uric acid following extensive hemorrhage. Am. J. Physiol. 214:1374–1377.PubMedGoogle Scholar
  11. 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
  12. 12.
    Neely, J. R., Liebermeister, H., Battersby, E. J., and Morgan, H. E. 1967. Effects of pressure development on oxygen consumption by isolated rat heart. Am. J. Physiol. 212:804–814.PubMedGoogle Scholar
  13. 13.
    Hughes, B. P. 1962. A method for the estimation of serum creatine kinase and its use in comparing creatine kinase and aldolase activity in normal and pathological sera. Clin. Chim. Acta 7:597.PubMedCrossRefGoogle Scholar
  14. 14.
    Crowell, J. W., Jones, C. E., and Smith, E. E. 1969. Effect of allopurinol on hemorrhagic shock. Am. J. Physiol. 216:744–748.PubMedGoogle Scholar
  15. 15.
    De Wall, R. A., Vasko, K. A., Stanley, E. L., and Kezdi, P. 1971. Responses of the ischemic myocardium to allopurinol. Am. Heart J. 82:362–370.CrossRefGoogle Scholar
  16. 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

Copyright information

© Springer Science+Business Media New York 1985

Authors and Affiliations

  • Joe M. McCord
    • 1
  • Ranjan S. Roy
    • 1
  • Stephen W. Schaffer
    • 2
  1. 1.Department of Biochemistry, College of MedicineUniversity of South AlabamaMobileUSA
  2. 2.Department of Pharmacology, College of MedicineUniversity of South AlabamaMobileUSA

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