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Oxygen-Free Radicals at Myocardial Level: Effects of Ischaemia and Reperfusion

  • Roberto Ferrari
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 366)

Abstract

In the past several years, much interest has arisen over the involvement of free radical metabolism in the biochemical events associated with ischaemia and reperfusion injury to the heart. A decade ago, it would have been difficult to propose a single plausible mechanism to implicate oxygen in injury since it was generally held that the determinants of the degree of damage after a coronary occlusion were simply the oxygen supply vs the oxygen demand of the heart. However, it has been recently recognized that the myocardium cannot recover without the restitution of adequate coronary flow, or in other words: without being reperfused1. However, reperfusion may result in numerous negative consequences and it has been shown that reperfusion of heart muscle after > 60 min of ischaemia is associated with release of enzymes, transient rise of diastolic pressure, persistent reduction of contractility, influx of calcium, alteration of mitochondrial function, disruption of cell membranes, and eventual necrosis of at least a proportion of tissue2–8.

Keywords

Electron Paramagnetic Resonance Myocardial Ischaemia Reperfusion Injury Xanthine Oxidase Reperfusion Damage 
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.
    J.M. Turner and A. Boveris, Generation of superoxide anion by NADH dehydrogenase of bovine heart mitochondria, Biochem J 1291: 421 (1980).Google Scholar
  2. 2.
    R. Ferrari, S. Bongrani and F. Cucchini, Effects of molecular oxygen and calcium on heart metabolism during reperfusion, in: M.E. Bertrand ed., Coronary Arterial Spasm, 46 (1982).Google Scholar
  3. 3.
    N. Nohl, The biochemical mechanism of the formation of reactive oxygen species in heart mitochondria, in: C.M. Caldarera and P. Harris, eds., “Advances in Studies on Heart Metabolism,” Cooperativa Libraria Universitaria Editrice, Bologna, 413 (1982).Google Scholar
  4. 4.
    H. Otani, H. Tanaka, T Inove et al., In vitro studies on contribution of oxidative metabolism of isolated rabbit heart mitochondria to myocardial reperfusion injury, Circ Res 55:168 (1984).PubMedCrossRefGoogle Scholar
  5. 5.
    R.W. Egan, J. Paxton and F.A. Kuehl Jr., Mechanisms for the irreversible self deactivation of prostaglandin synthetase, J Biol Chem 251: 7329 (1976).PubMedGoogle Scholar
  6. 6.
    D.E. Chambers, D.A. Parks, G. Patterson, et al., Xanthine oxidase as a source of free radical in myocardial ischaemia, J Mol Cell Cardiol 17:145 (1985).PubMedCrossRefGoogle Scholar
  7. 7.
    S.W. Werns, M.J. Shea, S.E. Mitsos, et al., Reduction of the size of infarction by allopurinol in the ischaemic reperfused canine heart, Circulation 73: 518 (1986).PubMedCrossRefGoogle Scholar
  8. 8.
    S. Akizuki, S. Yoshida, D.E. Chambers, et al., Infarct size limitation by the xanthine oxidase inhibitor, allopurinol, in closed chest dogs with small infarcts, Cardiovasc Res 19: 686 (1985).PubMedCrossRefGoogle Scholar
  9. 9.
    W.L. Arnold, R.H. de Wall, P. Keydi, et al., The effect of allopurinol on the degree of early myocardial ischaemia, Am Heart J 99: 614 (1985).CrossRefGoogle Scholar
  10. 10.
    J.R. Parratt and C.L. Wainwright, Failure of allopurinol and a spin-trapping agent N-t-alpha-phenyl nitrone to modify significantly ischaemia and reperfusion-induced arrhythmias, Br J Pharmacol 91: 49 (1987).PubMedCrossRefGoogle Scholar
  11. 11.
    J.P. Kehrer, H. Piper and H. Sies, Xanthine oxidase is not responsible for reoxygenation injury in isolated perfused rat heart, Free Rad Res Commun 3: 69 (1987).CrossRefGoogle Scholar
  12. 12.
    U.A.S. Al-Khalidi and T.H. Chaglassian, The species distribution of xanthine oxidase, Biochem J 97: 318 (1965).PubMedGoogle Scholar
  13. 13.
    J.M. Downey, D.J. Hearse and D.M. Yellon, The role of xanthine oxidase during myocardial ischaemia in several species including man, J Mol Cell Cardiol 20(suppl.II): 55 (1988).PubMedCrossRefGoogle Scholar
  14. 14.
    T.D. Enhgerson, T.G. McKelvey, D.B. Rhynie, et al., Conversion of xanthine dehydrogenase to oxidase in ischaernic rat tissue, J Clin Invest 79: 2564 (1987).Google Scholar
  15. 15.
    S.J. Weiss, M.B. Lampert, Test ST., Long-lived oxidants generated by human neutrophils: characterization and bioactivity, Science 222: 625 (1983).PubMedCrossRefGoogle Scholar
  16. 16.
    R. Ferrari, C. Ceconi, S. Curello, C. Guarnieri, C.M. Caldarera, A. Albertini and O. Visioli, Oxygen mediated myocardial damage during ischaemia and reperfusion: role of the cellular defences against oxygen toxicity, J. Moll. Cell. Cardiol. 17:937 (1985).CrossRefGoogle Scholar
  17. 17.
    R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, G. Agnoletti, G.M. Boffa and O. Visioli, Intracellular effects of myocardial ischaemia and reperfusion: role of calcium and oxyge, Eur. Heart J. 7:3 (1986).PubMedGoogle Scholar
  18. 18.
    R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni and D. Medici, Oxygen free radicals and reperfusion injury: effect of ischaemia and reperfusion on the cellular ability to neutralise oxygen toxicity, J. Mol. Cell. Cardiol. 18: 67 (1986).PubMedCrossRefGoogle Scholar
  19. 19.
    S. Curello, C. Bigoli, R. Ferrari, A. Albertini and C. Guarnieri, Changes in the cardiac glutathione status after ischaemia and reperfusion, Experientia 41:42 (1985).PubMedCrossRefGoogle Scholar
  20. 20.
    R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, E. Pasini, F. De Giuli and A. Albertini, Role of oxygen free radicals in ischaemic and reperfused myocardium, Am. J. Clin. Nutr. 53: 215 (1991).Google Scholar
  21. 21.
    R. Ferrari, The role of free radicals in ischaemic myocardium, British Journal of Clinical Practice 44: 301 (1990).PubMedGoogle Scholar
  22. 22.
    R.B. Jennings, Myocardial ischaemia. Observations, definitions and speculation, J Mol Cell Cardiol 1: 345 (1970).CrossRefGoogle Scholar
  23. 23.
    J.M. McCord, Free radicals and myocardial ischaemia: overview and outlook, Free Radic Biol Med 4: 9 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    Nohl H. The biochemical mechanism of the formation of reactive oxygen species in heart mitochondria in: C.M. Caldarera and P. Harris, eds., “Advances in Studies on Heart Metabolism,” Cooperativa Libraria Universitaria Editrice, Bologna, 413 (1982).Google Scholar
  25. 25.
    R. Ferrari, S. Bongrani F. Cucchini, F. Di Lisa, C. Guarnieri and O. Visioli, Effect of molecular oxygen and calcium on heart metabolism during reperfusion, in: Bertrand ME, ed., “Coronary arterial spasm,” Lille, France, 46 (1982).Google Scholar
  26. 26.
    H. Otani, H. Tanaka, T. Inove, et al., In vitro studies on contribution of oxidative metabolism of isolated rabbit heart mitochondria to myocardial reperfusion injury, Circ Res 55:168 (1984).PubMedCrossRefGoogle Scholar
  27. 27.
    C. Guarnieri C. Ceconi, C. Muscari and F. Flamigni, Influence of oxygen radicals on heart metabolism, in: C.M. Caldarera and P. Harris, eds., “Advances in studies on heart metabolism,” Clueb, Bologna (1982).Google Scholar
  28. 28.
    C. Ceconi, S. Curello, A. Albertini and R. Ferrari, Effect of lipid peroxidation on heart mitochondria oxygen consuming and calcium transporting capacities, Mol Cell Biochem 81:131 (1988).PubMedCrossRefGoogle Scholar
  29. 29.
    O.D. Saugstad and A.O. Aasen, Plasma hypoxanthine concentrations in pigs a prognostic aid in hypoxia, Eur Surg Res 12:123 (1980).PubMedCrossRefGoogle Scholar
  30. 30.
    R. A. de Wall, K.A. Vasko, E.L. Stanley and P. Kezdi, Responses of the ischaemic myocardium to allopurinol, Am Heart J 82:362 1971).CrossRefGoogle Scholar
  31. 31.
    C.E. Jones, J. W. Crowell and E.E. Smith, Significance of increased blood uric acid following extensive hemmorrhage, Am J Physiol 214:1374 (1968).PubMedGoogle Scholar
  32. 32.
    D.N. Granger, G. Rutilio and J.M. Mc Cord, Superoxide radicals in feline intestinal ischaemia, Gastroenterology 81:22 (1981).PubMedGoogle Scholar
  33. 33.
    A.S. Manning, D.J. Coltart and D.J. Hearse, Ischaemia and reperfusion induced arrhythmias in the rat. Eflect of xanthine oxidase inhibition with allopurinol, Circ Res 55:545 (1984).PubMedCrossRefGoogle Scholar
  34. 34.
    R.A. Kloner, Introduction to the role of oxygen radicals in myocardial ischaemia and infarction., Free Radic Biol Med 4:5 (1988).PubMedCrossRefGoogle Scholar
  35. 35.
    J.M. Downey, D.J. Hearse and D.M. Yellon, The role of xanthine oxidase dunng myocardial ischaemia in several species including man, J Mol Cell Cardiol 20(suppl II):55 (1988).PubMedCrossRefGoogle Scholar
  36. 36.
    W.L. Arnold, R.H. de Wall, P. Keydi and H.H. Eward, The effect of allopurinol on the degree of early myocardial ischaemia, Am Heart J 99:614 (1985).CrossRefGoogle Scholar
  37. 37.
    J.R. Parrtt and C.L. Wainwright, Failure of allopurinol and a spin-trapping agent N-t-alpha-phenyl nitrone to modify significantly ischaemia and reperfusion-induced arrhythmias, Br J Pharmacol 91:49 (1987).CrossRefGoogle Scholar
  38. 38.
    J. Podzuweit, W. Braun, A. Muller and W. Schaper, Arrhythmias and infarction in the ischaemic pig heart are not mediated by xanthine-derived free oxygen radicals, Circulation 74(suppl II):311 (1986).Google Scholar
  39. 39.
    J.P. Kehrer, H. Piper and H. Sies, Xanthine oxidase is not responsible for reoxygenation injury in isolated-perfused rat heart, Free Radic Res Commun 3:69 (1987).PubMedCrossRefGoogle Scholar
  40. 40.
    K.A. Reimer and R.B. Jennings, Failure of xanthine oxidase inhibitor allopurinol to limit infarct size after ischaemia and reperfusion in dogs, Circulation 71:1069 (1985).PubMedCrossRefGoogle Scholar
  41. 41.
    J.L. Romson, B.G. Hook, S.L. Kunkel, G.R. Abrams, M.A. Schork and B.R. Lucchesi, Reduction of the extent of ischaemic injury by neutrophil deplelion in the dog, Circulation 62:1016 (1983).CrossRefGoogle Scholar
  42. 42.
    A. Manning, Reperfusion induced arrhythmias: do free radicals play a critical role? Free Radic Biol Med 4:305 (1988).PubMedCrossRefGoogle Scholar
  43. 43.
    R.L. Engler, G.W. Schmid Schonbein and R.S. Pavelec, Leucocyte capillary plugging in myocardial ischaemia and reperfusion in the dog, Am J Pathol 111:98 (1983).PubMedGoogle Scholar
  44. 44.
    K.M. Mullane, N. Read, J.A. Salmon and S. Moncada, Role of leukocytes in acute myocardial infarction in anesthetized dogs: relationship to myocardial salvage by anti-inflammatory drugs, J. Pharmacol Exp Ther 228:510 (1984).PubMedGoogle Scholar
  45. 45.
    Y. Qui, M. Galinanes, R. Ferrari, A. Cargnoni, A. Erzin and D.J. Hearse, PEG-SOD improves postischemie functional recovery and anti-oxidant status in the isolated blood-perfused rabbit heart, Americam Journal of Physiology 263:H1243 (1992).Google Scholar
  46. 46.
    H.A. Kontos, E.P. Wei and J.T. Povlishock, Cerebral arteriolar damage by arachidonic acid and prostaglandin G2, Science 209:156 (1983).Google Scholar
  47. 47.
    A. Schomig, D.M. Dart, R. Dietz, E. Mayer and W. Kubier, Release of endogenous catecholamines in the ischaemic myocardium of the rat, Circ Res 55: 689 (1984).PubMedCrossRefGoogle Scholar
  48. 48.
    P.K. Singal, R.E. Beamish and N.S. Dhalla, Potential oxidative pathways of catecholamines in the formation of lipid peroxides and genesis of heart disease, Adv Exp Med Biol 161:391 (1983).PubMedCrossRefGoogle Scholar
  49. 49.
    R. Julicher, L. Sterrenberg, J. Koomen, A. Bast and J. Noordhoek, Evidence for lipid peroxidation during the calcium paradox in vitamin E-deficient rat heart, Arch Pharmacol 326:87 (1984).CrossRefGoogle Scholar
  50. 50.
    R. Ferrari, C. Ceconi, A. Cargnoni, S. Curello and T. Ruigrok, No evidence of oxidative stress during calcium paradox, Basic Res Cardiol 84: 396 (1989).PubMedCrossRefGoogle Scholar
  51. 51.
    R.A. Wolf and R.W. Gross, Identification of a neutral phospholipase C which hydrolyzes choline giycerophospholipids and plasmalogen selective phospholipase A2 in canine myocardium, J Biol Chem 260:7295 (1985).PubMedGoogle Scholar
  52. 52.
    V.E. Kagan, V.M. Savov, V.V. Didenko, Yu V. Arkhypenko and F.Z. Meerson, Calcium and lipid peroxidation in mitochondrial and microsomal membranes ofthe heart, Bull Exp Biol Med 95:458 (1983).CrossRefGoogle Scholar
  53. 53.
    I.M. McCord and I. Fridovich, Superoxide dismutase: An enzymatic function for erythrocuprein(hemocuprein), J Biol Chem 244: 6049 (1969).PubMedGoogle Scholar
  54. 54.
    D. Roos, R.S. Weening and S.R. Wyss, Protection of human neutrophils by endogenous catalase: studies with cells from catalase-deficient individuals. J Clin Invest 65:1515 (1980).PubMedCrossRefGoogle Scholar
  55. 55.
    B. Chance, H. Sies and A. Boveris, Hydroperoxide metabolism in mammalian organs. Physiol Rev 59:527 (1979).PubMedGoogle Scholar
  56. 56.
    R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, A. Albertini and O. Visioli, Oxygen utilization and toxicity at myocardial level, in: G. Benzi, L. Packer and N. Siliprandi, eds., “Biochemical aspects of physical exercise,” Elsevier, Amsterdam, 145 (1986).Google Scholar
  57. 57.
    S. Curello, C. Ceconi, C. Bigoli, R. Ferrari, A. Albertini and C. Guarnieri, Change in the cardiac glutathione status aner ischaemia and reperfusion, Experientia 41:42 (1985).PubMedCrossRefGoogle Scholar
  58. 58.
    S. Curello, C. Ceconi, A. Cargnoni, R. Ferrari and A. Albertini, Improved procedure for determining glutathione plasma as an index of myocardial oxidative stress, Clin Chem 33:1448 (1987).PubMedGoogle Scholar
  59. 59.
    S. Curello, C. Ceconi, D. Medici and R. Ferrari, Oxidative stress during myocardial ischaemia and reperfusion: experimental and clinical evidences, J Appl Cardiol 1: 311 (1986).Google Scholar
  60. 60.
    R. Ferrari, O. Visioli, C.M. Caldarera and W.G. Nayler, Vitamin E and the heart possible role as antioxidant, Acta Vitaminol Enzymol 5:11 (1982).Google Scholar
  61. 61.
    C. Guarnieri, R. Ferrari, O. Visioli, C.M. Caldarera and W.G. Nayler, Effect of alpha-tocopherol on hypoxic reperfused and reoxygenated rabbit heart, J Mol Cell Cardiol 10:893 (1978).PubMedCrossRefGoogle Scholar
  62. 62.
    R. Ferrari, A. Cargnoni, C. Ceconi, S. Curello, A. Albertini and O. Visioli, Role of oxygen in myocardial ischaemic and reperfusion damage: protective effects of vitamin E, in: Hayaishi O, Mino M, eds., “Clinical and nutritional aspects of vitamin E,” Elsevier, Amsterdam 209 (1987).Google Scholar
  63. 63.
    C. Guarnieri, F. Flamigni, C. Rossoni-Caldarera and R. Ferrari, Myocardial mitochondrial function in alpha-tocopherol deficient and refed rabbits, in: “Advances in myocardiology,” Vol. 3, Plenum Press, New York, 621 (1982).Google Scholar
  64. 64.
    R. Ferrari, A. Cargnoni, C. Ceconi, S. Curello, A. Albertini and O. Visioli, Role of oxygen in the myocardial ischaemic and reperfusion damage: protective effects of vitamin E, in: O. Hayaishi, M. Mino, eds., “Clinical and biochemical aspects of vitamin E,” Elsevier, Amsterdam, 209 (1987).Google Scholar
  65. 65.
    Gruppo Italiano per lo Studio della streptochinasi nell’infarto miocardico(GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction, Lancet 22: 397.Google Scholar
  66. 66.
    TIMI Study Group. The thrombolysis in myocardial infarction(TIMI) trial: phase 1 findings, N Engl J Med 312: 932 (1985).Google Scholar
  67. 67.
    R. Ferrari S. Curello A. Cargnoni, E. Condorelli, S. Belloli, A. Albertini and O. Visioli, Metabolic changes durng post-ischaemic reperfusion, J Mol Cell Cardiol 20: 119 (1988).PubMedCrossRefGoogle Scholar
  68. 68.
    D.J. Hearse, Ischaemia, reperfusion, and the determinants of tissue injury, Cardiovasc Drugs Ther 4: 767 (1990).PubMedCrossRefGoogle Scholar
  69. 69.
    K.A. Reimer and R.B. Jennings, Failure xanthine oxidase inhibitor allopurinol to limit infarct size aftr ischaemia and reperfusion in dogs, Circulation 71:1069 (1985).PubMedCrossRefGoogle Scholar
  70. 70.
    K.P. Gallagher, A.J. Buda, D. Pace, R.A. Gerren and M. Shlafer, Failure of superoxide dismutase reduces oxygen-free radical concentrations in reperfused myocardium, J Clin Invest 73:1065 (1986).Google Scholar
  71. 71.
    J.L. Zweier, J.T. Flaherty and M.L. Weisfeldt, Direct measurement of free radical generation following reperfusion of ischemic myocardium, Proc Natl Acad Sci USA 84:1404 (1987).PubMedCrossRefGoogle Scholar
  72. 72.
    J.M. Luber, P.S. Rao, and M.S. Crowder, Identification of free radicals produced during myocardial ischemia and reperfusion using electron paramagnetic resonance spectroscopy and high precision liquid chromatography, J. Thorac Cardiovasc Surg (in press).Google Scholar
  73. 73.
    C.M. Arroyo, J.H. Kramer, B.F. Dickens and W.B. Weglicki, Identification of free radicals in mypcardial ischemia/reperfusion by spin trapping with nitron DMPO. FEBS Lett 221:101 (1987)Google Scholar
  74. 74.
    C.M. Arroyo, J.H. Kramer, R.H. Leiboff, G.W. Mergner, B.F. Diskens and W.B. Weglicki, Spin trapping of oxygen and carbon-centered free radicals in ischaemic canine myocardium, Free Radic Biol Med 3:313 (1987).PubMedCrossRefGoogle Scholar
  75. 75.
    P.B. Garlick, M.J. Davies, D.J. Hearse and T.F. Slater, Direct detection of free radicals in the reperfused rat heart using electron spin resonance spectroscopy, Circ Res 61:757 (1987).PubMedCrossRefGoogle Scholar
  76. 76.
    R. Bolli, B.S. Patel, M.O. Jeroudi, E.K. Lai and P.B. McCay, Demonstration of free radicals generation in “stunned” myocardium of intact dogs with use of the spin trap Alpha-phenyl n-ter-butyl nitrone, J Clin Invest 82:476 (1988).PubMedCrossRefGoogle Scholar
  77. 77.
    W. Limm, M. Mugiishi, L.H. Piette and J.J. Mc Namara. Quantitative assessment of free radical generation during ischemia and reperfusion in the isolated rabbit heart, “Proc Fourth Int Cong Oxygen Radicals”, La Jolla CA (1987).Google Scholar
  78. 78.
    Y. Gauduel and M.A. Duvelleroy, Role of oxygen radicals in cardiac injury due to reoxygenation, J Mol Cell Cardiol C. 16: 459 (1984).CrossRefGoogle Scholar
  79. 79.
    C. Guarnieri, F. Flamigni and C.M. Caldarera, Role of oxygen in the cellular damage induced by reoxygenation of hypoxic heart, J Mol Cell Cardiol 12: 797 (1980).PubMedCrossRefGoogle Scholar
  80. 80.
    F.Z. Meerson, V.E. Kagan, YuP. Kozlov, et al., The role of lipid peroxidation in pathogenesis of ischaemic damage and the antioxidant protection of the heart, Basic Res Cardiol 77: 465The role of lipid peroxidation in pathogenesis of ischaemic damage and the antioxidant protection of the heart, Basic Res Cardiol 77: 465 (1982).Google Scholar
  81. 81.
    J.M.C. Gutteridge and G.J. Quinlan, Malondialdehyde formation from lipid peroxides in the thiobarbituric acid test: the role of lipid radicals, iron salts and metal chelators, J Appl Biochem 5: 293 (1983).PubMedGoogle Scholar
  82. 82.
    T.L. Dormandy, Free radical oxidation and anti-oxidants, Lancet 1: 647 (1978).PubMedCrossRefGoogle Scholar
  83. 83.
    C. Ceconi, A. Cargnoni, E. Pasini, E. Condorelli, S. Curello and R. Ferrari, Evaluation of phospholipid peroxidation as malondialdehyde during myocardial ischaemia and reperfusion injury, Am J Physiol 260: 105 (1991).Google Scholar
  84. 84.
    J.D. Adams, B.M. Lauterburg and J.R. Mitchell, Plasma glutathione and glutathione disulfide in the rat: regulation and response to oxidative stress, J Pharmacol Exp Ther 227 749 (1983).PubMedGoogle Scholar
  85. 85.
    R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, A. Albertini and O. Visioli, Molecular events occurring during post-ischaemic reperfusion, in: N.S. Dhalla, I.R. Innes and R.E. Beanish, eds., “Myocardial ischaemia,” Nijhoff Publishing, Boston, 67 (1987).Google Scholar
  86. 86.
    R. Ferrari, S. Curello, C. Ceconi, A. Cargnoni, E. Condorelli and A. Albenini, Alterations of glutathione status during myocardial ischaemia and reperfusion, in: P.K. Singal, ed., “Oxygen radicals in the pathophysiology of heart disease,“ Vol 10. Kluwer Academic Publisher, Amsterdam, 145 (1988).CrossRefGoogle Scholar
  87. 87.
    R. Ferrari, O. Alfieri, S. Curello, C. Ceconi, A. Cargnoni, P. Marzollo, A. Pardini, E. Caradonna and O. Visioli, Occurrence of oxidative stress during reperfusion of the human heart, Circulation 81:201 (1990).PubMedCrossRefGoogle Scholar
  88. 88.
    R. Ferrari, C. Ceconi, S. Curello, A. Cargnoni, F. De Giuli and O. Visioli, Occurrence of oxidative stress during myocardial reperfusion, Mol. Cell. Biochem, 111:61 (1992).PubMedCrossRefGoogle Scholar
  89. 89.
    R. Ferrari, Importance of oxygen-free radicals during ischaemia and reperfusion in the experimental and clinical setting, The American Journal of Cardiovascular Pathology 4 (1992).Google Scholar
  90. 90.
    S. Curello, C. Ceconi, F. De Giuli, A.F. Panzali, B. Milanesi, M. Calarco, Pardini, P. Marzollo, O. Alfieri, R. Ferrari and O. Visioli, Oxidative stress during reperfusion of human hearts: potential sources of oxygen-free radicals, Manuscript submitted to Circulation.Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Roberto Ferrari
    • 1
    • 2
  1. 1.University of BresciaItaly
  2. 2.Fondazione Clinica del Lavoro di PaviaCentro di Fisiopatologia Cardiovascolare “S. Maugeri”Gussago (Brescia)Italy

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