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Myocardial Salvage by the Free Radical Scavenging Actions of Xanthine Oxidase Inhibitors

  • Dipak K. Das
  • Richard M. Engelman
  • Ronald Clement
  • Hajime Otani
  • M. Renuka Prasad
  • Parinam S. Rao
Part of the Basic Life Sciences book series (BLSC, volume 49)

Abstract

It is well established that oxygen-derived free radicals play a crucial role in the pathogenesis of ischemic-reperfusion injury.1 However, the source of these radicals remains unknown. McCord2 has proposed that oxygen radicals are generated during reoxygenation of ischemic myocardium by the action of xanthine oxidase on hypoxanthine. A number of investigators supported this hypothesis based on their observations of allopurinol-mediated reduction of reperfusion injury.3 Recently, the beneficial action of allopurinol to salvage ischemic-reperfused myocardium has been challenged by Reimer et al.4 In addition, most of the mammalian hearts, with the exception of rat heart, have been found to contain negligible or no xanthine oxidase activity at all.5 The purpose of the present study was, therefore, to investigate the role of two xanthine oxidase inhibitors, allopurinol and oxypurinol, on the ischemic-reperfused heart and to explore their mechanisms of action. Our results suggest that these xanthine oxidase inhibitors salvage the ischemic-reperfused myocardium by scavenging the free radicals.

Keywords

Electron Paramagnetic Resonance Electron Paramagnetic Resonance Spectrum Xanthine Oxidase Electron Paramagnetic Resonance Signal Xanthine Oxidase Activity 
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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References

  1. 1.
    D. K. Das, R. M. Engelman, J. A. Rousou, R. H. Breyer, P. Otani, and S. Lemeshow, Pathophysiology of superoxide radical as potential mediator of reperfusion injury in pig heart, Basic Res. Cardiol, 81:155 (1986).CrossRefGoogle Scholar
  2. 2.
    J. M. McCord, Oxygen-derived free radicals in postischemic tissue injury, N. Engl. J. Med. 312:159 (1985).PubMedCrossRefGoogle Scholar
  3. 3.
    S. W. Werns, M. J. Shea, S. E. Mitsos, R. C. Dysko, J. C. Fantone, M. A. Schork, G. D. Abrams, B. Pitt, and B. R. Lucchesi, Reduction of the size of infarction by allopurinol in the ischemic-reperfused canine heart, Circulation 73:518 (1986).PubMedCrossRefGoogle Scholar
  4. 4.
    K. A. Reimer and R. B. Jennings, Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion, Circulation 71:1069 (1985).PubMedCrossRefGoogle Scholar
  5. 5.
    D. A. Parks and D. N. Granger, Xanthine oxidase: biochemistry, distribution and physiology, Acta Physiol. Scand. (Suppl) 548:87 (1986).Google Scholar
  6. 6.
    P. Otani, R. M. Engelman, J. A. Rousou, R. H. Breyer, S. Lemeshow, and D. K. Das, Cardiac performance during reperfusion improved by pre-treatment with oxygen free-radical scavengers, J. Thorac. Cardio-vasc. Surg. 91:290 (1986).Google Scholar
  7. 7.
    D. K. Das, R. M. Engelman, H. Otani, J. A. Rousou, R. H. Breyer, and S. Lemeshow, Effect of superoxide dismutase and catalase on myocardial energy metabolism during ischemia and reperfusion, Clin. Physiol. Biochem. 4:187 (1986).Google Scholar
  8. 8.
    D. A. Peterson, B. Kelly, and J. M. Gerrard, Allopurinol can act as an electron transfer agent, Biochem. Biophys. Res. Commun. 137:76 (1986).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • Dipak K. Das
    • 1
  • Richard M. Engelman
    • 1
  • Ronald Clement
    • 2
  • Hajime Otani
    • 1
  • M. Renuka Prasad
    • 1
  • Parinam S. Rao
    • 3
  1. 1.University of Connecticut School of MedicineFarmingtonUSA
  2. 2.Baystate Medical CenterSpringfieldUSA
  3. 3.Long Island Jewish Medical CenterNew Hyde ParkUSA

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