Importance of Electron Transfer through Allopurinol in Protection from Reperfusion Injury

  • D. A. Peterson
  • J. M. Gerrard
Part of the Developments in Cardiovascular Medicine book series (DICM, volume 86)


With the advent of organ transplantation and clinical intervention in ischemic states, the role of tissue reperfusion has assumed increasing importance. The pathological changes which can accompany reperfusion have been the focus of increasing interest. While the etiology of these changes is multifactorial, evidence has arisen from several laboratories that reduced oxygen species are involved. There are several intracellular sources which could produce reduced oxygen radicals, including prostaglandin synthetase, the cytochrome p450 system, the electron transport chain and xanthine oxidase. Because of the effectiveness of inhibitors of xanthine oxidase in blunting reperfusion damage in several organ systems, it has been postulated as a major source of these radicals. However, other interpretations could be drawn from this data. Using the heart as a focus of discussion, we shall study another possible effect of the most widely used xanthine oxidase inhibitor, allopurinol.


Infarct Size Electron Transport Chain Xanthine Oxidase Electron Transport System Xanthine Oxidase Inhibitor 
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  1. 1.
    McCord, J.M.: Oxygen-derived free radicals in post-ischemic tissue injury. N. Engl. J. Med. 312:159–163, 1985.PubMedCrossRefGoogle Scholar
  2. 2.
    Chambers, D.E., Parks, D.A., Patterson, G., Roy, R., McCord, J.M., Yoshida, S., Parmley, L.F. and Downey, J.M.: Xanthine oxidase as a source of free radical damage in myocardial ischemia. J. Mol. Cell Cardiol. 17:145–152, 1985.PubMedCrossRefGoogle Scholar
  3. 3.
    Werns, S.W., Shear, M.J., Mitsos, S.E., Dysko, R.C., Fantone, J.C., Schorr, M.A., Abrams, G.D., Pitt, B. and Lucchesi, B.R.: Reduction of the size of infarction by allopurinol in the ischemic-reperfused canine heart. Circulation 73:518–524, 1986.PubMedCrossRefGoogle Scholar
  4. 4.
    Manning, A.S., Coltart, D.J. and Hearse, D.J.: Ischemia and reperfusion induced arrhythmias in the rat. Effects of xanthine oxidase inhibition with allopurinol. Circ. Res. 55:545–548, 1984.PubMedCrossRefGoogle Scholar
  5. 5.
    Eaton, J.W., Peterson, D.A., Elsperger, J., Asinger, R. and Homans, D.: Reduction of ventricular fibrillation during myocardial reperfusion in the dog by pretreatment with allopurinol. Fed. Proc. #5058, 1985.Google Scholar
  6. 6.
    Peterson, D.A., Asinger, R.W., Elsperger, J., Homans, D.C. and Eaton, J.W.: Reactive oxygen species may cause myocardial reperfusion injury. Biochem. Biophys. Res. Commun. 127:87–93, 1985.PubMedCrossRefGoogle Scholar
  7. 7.
    Stewart, J.R., Crute, S.L., Laughlin, U., Hess, M.L. and Greenfield, L.J.: Prevention of free radical-induced myocardial reperfusion injury with allopurinol. J. Thorac. Cardiovasc. Surg. 90:68–72, 1985.PubMedGoogle Scholar
  8. 8.
    Myers, C.L., Weiss, S.J., Kush, M.M., Sheppard, B.M. and Shlafer, M.: Effects of supplementary hypothermic crystalloid car-dioplegic solution with catalase, superoxide dismutase, allopurinol or deferoxamine on functional recovery of globally ischemic and reperfused isolated hearts. J. Thoracic Cardiovasc. Surg. 91:281–289, 1986.Google Scholar
  9. 9.
    Reimer, K.A. and Jennings, R.B.: Failure of the xanthine oxidase inhibitor allopurinol to limit infarct size after ischemia and reperfusion in dogs. Circulation 71:1069–1075, 1985.PubMedCrossRefGoogle Scholar
  10. 10.
    Eddy, L., Stewart, J., Jones, H., Yellon, D., McCord, J. and Downey, J.: Xanthine oxidase is detected in ischemic rat heart but not human hearts. The Physiologist 129:166, 1987.Google Scholar
  11. 11.
    Grum, CM., Ragsdale, R.A., Ketai, C.H. and Schlafer, M.: Absence of xanthine oxidase or xanthine dehydrogenase in the rabbit myocardium. Biochem. Biophys. Res. Commun. 141:1104–1108, 1986.PubMedCrossRefGoogle Scholar
  12. 12.
    England, M.D., Cavarochi, N.C., O’Brien, J.F., Solis, E., Pluth, J.R., Orszular, T.A., Kaye, M.P. and Scraff, H.V.: Influence of antioxidants (mannitol and allopurinol) on oxygen free radical generation during and after cardiopulmonary bypass. Circulation 74(111):34–37, 1986.Google Scholar
  13. 13.
    Kane, J.J., Murphy, M.L., Bissett, J.K., de Soyza, N., Doherty, J.E. and Straub, K.D.: Mitochondrial function, oxygen extraction, epicardial ST segment changes and tritiated digoxin distribution after reperfusion of ischemic myocardium. Am. J. Cardiol. 36:218–224, 1975.PubMedCrossRefGoogle Scholar
  14. 14.
    Wood, J.A., Hanley, H.G., Entman, M.L., Hartley, C.J., Swain, J.A., Bush, U., Chang, C, Lewis, R.M., Morgan, W.J. and Schwartz, A.: Biochemical and morphological correlates of acute experimental myocardial ischemia in the dog IV. Early mechanisms during very early ischemia. Circ. Res. 44:52–62, 1979.PubMedCrossRefGoogle Scholar
  15. 15.
    Peterson, D.A. and Gerrard, J.M.: A hypothesis for a role for unsaturated fatty acids in electron transport and its potential application to understanding the mitochondrial respiratory chain. Med. Hypothesis 6:491–499, 1980.CrossRefGoogle Scholar
  16. 16.
    Peterson, D.A., Kelly, B. and Gerrard, J.M.: Allopurinol can act as an electron transfer agent. Is this relevant during reperfusion injury? Biochem. Biophys. Res. Commun. 137:76–79, 1986.PubMedCrossRefGoogle Scholar
  17. 17.
    Moorhouse, P.C., Grootveld, M., Halliwell, B., Quinlan, J.B. and Gutteridge, J.M.C.: Allopurinol and oxypurinol are hydroxyl radical scavengers. FEBS Lett. 213:23–28, 1987.PubMedCrossRefGoogle Scholar
  18. 18.
    Okamoto, F., Allen, B.S., Buciberg, G.D., Leaf, J. and Bugyi, H.: Reperfusate composition: supplemental role of intravenous and intracoronary coenzyme Q10 in avoiding reperfusion damage. J. Thoracic Cardiovasc. Surg. 92(3 Pt 2):573–582, 1986.Google Scholar
  19. 19.
    Konishi, T., Nakamura, Y., Konishi, T. and Kawai, C: Improvement of left ventricular function during reperfusion with coenzyme Q10 in isolated working rat heart. Cardiovasc. Res. 19: 38–43, 1985.PubMedCrossRefGoogle Scholar
  20. 20.
    Takada, M., Ikenoya, S., Yuzurika, T. and Katayama, K.: Studies on reduced and oxidized co-enzyme Q (ubiquinones) II. The determination of oxidation reduction levels of co-enzyme Q in mitochondria microsomes and plasma by high performance liquid chromatography. Biochem. Biophys. Acta 679:308–314, 1982.PubMedGoogle Scholar
  21. 21.
    Sugiyama, S., Kitagawa, M., Aizwa, T., Suzuki, K. and Izawa, Y.: Antioxidant effect of coenzyme Q10. Experientia 36:1002–1003, 1980.PubMedCrossRefGoogle Scholar
  22. 22.
    Folkers, K., Watanabe, T. and Kaji, M.: Critique of co-enzyme Q10 in biochemical and biological research and in ten years of clinical research on cardiovascular disease. J. Mol. Med. 2: 431–460, 1977.Google Scholar
  23. 23.
    Barnard, R.J., Okamoto, F., Buckberg, G.C., Sjostrand, F., Rosenkranz, E.R., Vinten-Johansen, J., Allen, B.S. and Leaf, S.: Studies of controlled reperfusion after ischemia III. Histochemical studies: Inability of triphenyltetrazolium chloride non-staining to define tissue necrosis. J. Thoracic Cardiovasc. Surg. 92:502–512, 1986.Google Scholar
  24. 24.
    Fallon, J.T.: In: Myocardial Infarction: Measurement and Intervention (Ed. G.S. Wagner), Martinus Nijhoff Publishers, The Hague, 1982, pp. 373–384.CrossRefGoogle Scholar
  25. 25.
    Corr, P.B., Penkoske, P.B. and Sobel, B.E.: Adrenergic influences on arrhythmias due to coronary occlusion and reperfusion. Br. Heart J. 40(Suppl. l):62–70, 1978.Google Scholar
  26. 26.
    Culling, W., Penny, W.J., Lewis, M.J., Middleton, K. and Sheridan, D.J.: Effects of myocardial catecholamine depletion on cellular electrophysiology and arrhythmias during ischemia and reperfusion. Card. Res. 18:675–682, 1984.CrossRefGoogle Scholar
  27. 27.
    Hearse, D.J., Manning, A.S., Downey, J.M. and Yellon, D.M.: Xanthine oxidase: a critical mediator of myocardial injury during ischemia and reperfusion? Acta Physiol. Scand. Suppl. 548:65–78, 1986.PubMedGoogle Scholar
  28. 28.
    Singal, P.K., Dhillon, K.S., Beamish, R.E., Kapur, N. and Dhalla, N.S.: Myocardial cell damage and cardiovascular changes due to I.V. infusion of adrenochrome in rats. Br. J. Exp. Pathol. 63:167–176, 1982.PubMedCentralPubMedGoogle Scholar
  29. 29.
    Peterson, D.A. and Gerrard, J.M.: Reduction of a metal or disulfide bond associated with the receptor: A general hypothesis for the mechanism of action of adrenergic agents. Med. Hypothesis 22:35–44, 1987.CrossRefGoogle Scholar
  30. 30.
    Singal, P.K., Kapur, N., Beamish, R.E., Das, P.D. and Dhalla, N.: Antioxidant protection against epinephrine-induced arrhythmias. In: Stress and Heart Disease (Eds. R. Beamish, P.K. Singal and N.S. Dhalla), Martinus Nijhoff Publishing, Boston, 1985.Google Scholar
  31. 31.
    Nagai, S., Niyazaki, Y., Ogawa, K., Satake, T., Sugiyama, S. and Ozawa, T.: The effect of coenzyme Q10 on reperfusion injury in canine myocardium. J. Mol. Cell. Cardiol. 17:873–884, 1985.PubMedCrossRefGoogle Scholar
  32. 32.
    Ajiora, M., Nagai, S., Ogawa, K., Satake, T., Sugiyama, S. and Ozawa, T.: The role of phospholipase in the genesis of reperfusion arrhythmia. J. Electrocardiol. 19:165–172, 1986.CrossRefGoogle Scholar
  33. 33.
    Godin, D.V., Bhimji, S. and McNeil, J.H.: Effects of allopurinol pretreatment on myocardial ultrastructure and arrhythmias following coronary artery occlusion and reperfusion. Virchows Arch. (Cell Pathol.) 52:327–334, 1986.CrossRefGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1988

Authors and Affiliations

  • D. A. Peterson
    • 1
    • 2
  • J. M. Gerrard
    • 1
    • 2
  1. 1.Research DivisionV. A. Medical CenterMinneapolisUSA
  2. 2.Manitoba Institute of Cell BiologyUniversity of ManitobaWinnipegCanada

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