The Post Treatment Experiment: An Operational Definition of Reperfusion Injury
Part of the
Basic Life Sciences
book series (BLSC, volume 49)
During the past few years evidence for a remarkable hypothesis about the pathophysiology of ischemia and reperfusion has begun to accumulate.1–5 The hypothesis states that significant tissue damage resulting from a period of tissue ischemia, followed by reperfusion, may actually occur during the reperfusion phase, rather than during the period of ischemia, and may be caused by oxyen-derived free radicals. This concept has been described as the oxygen paradox,6, 7 namely, that although restoration of oxygen supply to ischemic tissue is necessary for return of normal function, oxygen may simultaneously participate in certain deleterious chemical reactions. Such paradoxical oxygen toxicity occurring during reperfusion involves, not molecular oxygen, but rather the partially reduced oxygen species: superoxide anions, hydrogen peroxide, and hydroxyl radicals. These species are capable of initiating chain reactions that chemically modify cellular proteins, lipids, and amino acids to produce what is referred to as reperfusion injury.
KeywordsReperfusion Injury Reperfusion Phase Total Circulatory Arrest Initiate Chain Reaction Significant Tissue 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.
J.M. McCord, Oxygen-derived free radicals in postischemic tissue injury, N. Eng. J. Med
. 312:159 (1985).CrossRefGoogle Scholar
B.C. White, S.D. Aust, K.E. Arfors, and L.D. Aronson, Brain injury by ischemic anoxia: Hypothesis extension—a tale of two ions?, Ann. Emerg. Med.
13:862 (1984).PubMedCrossRefGoogle Scholar
CF. Babbs, Role of iron ions in the genesis of reperfusion injury following successful cardioipulmonary resuscitation: Preliminary data and a biochemical hypothesis, Ann. Emerg. Med.
14:777 (1985).PubMedCrossRefGoogle Scholar
C. Guarnieri, F. Flamigni, and CM. Caldarera, Role of oxygen in the cellular damage induced by re-oxygenation of hypoxic heart, J. Mol. Cell. Cardiol.
12:797 (1980).PubMedCrossRefGoogle Scholar
F.Z. Meerson, V.E. Kagan, Y.P. Kozlov, L.M. Belkina, and Y.V. Arkhipenko, The role of lipid peroxidation in pathogenesis of ischemic damage and the antioxidant protection of the heart, Basic Res. Cardiol.
77:465 (1982).CrossRefGoogle Scholar
M.L. Hess and N.H. Manson, Molecular oxygen: Friend and foe. The role of the oxygen free radical system in the calcium paradox, the oxygen paradox, and ischemia/reperfusion injury, J. Mol. Cell. Cardiol.
16:969 (1984).PubMedCrossRefGoogle Scholar
CL. Myers, S.J. Weiss, M.M. Kirsh, and M. Shlafer, Involvement of hydrogen peroxide and hydroxyl radical in the oxygen paradox: reduction of creatinine kinase release by catalase, allopurinol, or deferoxamine, but not by superoxide dismutase, J. Mol. Cell. Cardiol.
17:675 (1985).PubMedCrossRefGoogle Scholar
L.H. Toledo-Pereyra, R.L. Simmons, and J.S. Najarian, Comparative effects of chlorpromazine, methylprednisolone and allopurinol during small bowel preservation, Am. J. Surg
. 126:631 (1973).PubMedCrossRefGoogle Scholar
A.A. Demetriou, P.K. Kagoma, S. Kaiser, E. Seifter, X.T. Niu, and S.M. Levenson, Effect of dimethylsulfoxide and glycerol on acute bowel ischemia in the rat, Am. J. Surg
. 149:91 (1985).PubMedCrossRefGoogle Scholar
S.D. Kompala, CF. Babbs, and K.E. Blaho, Effect of deferoxamine on late deaths following cardiopulmonary resuscitation in rats, Ann. Emerg. Med.
15:405 (1986).PubMedCrossRefGoogle Scholar
S.F. Badylak, CF. Babbs, C. Kougias, and K. Blaho, Effect of allopurinol and dimethylsulfoxide on long-term survival in rats after cardiorespiratory arrest and resuscitation, Amer. J. Emerg. Med
. 4:313 (1986).CrossRefGoogle Scholar
S.F. Badylak, A. Simmons, J. Turek, and CF. Babbs, Protection from reperfusion injury in the isolated rat heart by postischemic deferoxamine and oxypurinol administration, Cardiovasc. Res
. 21:500 (1987).PubMedCrossRefGoogle Scholar
G. Ambrosio, M.L. Weisfeldt, W.E. Jacobus, and J.T. Flaherty, Evidence for a reversible oxygen-radical mediated component of reperfusion injury: Reduction by recombinant human superoxide dismutase administered at the time of reflow, Circulation
75:282 (1987).PubMedCrossRefGoogle Scholar
J.M.C. Gutteridge, R. Richmond, and B. Halliwell, Inhibition of the iron-catalyzed formation of hydroxyl radicals from superoxide and lipid peroxidation by desferrioxamine, Biochem
J. 184:469 (1979).PubMedGoogle Scholar
© Plenum Press, New York 1988