Two major areas of clinical disease, the toxicity produced by exposure to elevated oxygen concentrations and the tissue damage caused by ischemia and reflow, may share a common pathogenesis involving the action of reactive oxygen species upon critical tissue molecules. Exposure to elevated concentrations of oxygen with or without mechanical ventilation remains the mainstay for treatment of infants and adults with respiratory failure, but continued exposure to high concentrations of oxygen often is responsible for the significant lung damage observed. Exposure of experimental animals to elevated oxygen concentrations produces massive pulmonary edema leading to systemic hypoxia and death of the animal. It is clear that reactive oxygen species must be the initiators of oxygen-induced lung damage in these experimental animals because mechanical ventilation is not employed. However, little is known about the molecular nature of the chemical alterations responsible for the toxicity. In addition, a number of lines of evidence indicate that reactive oxygen species are involved in tissue damage produced by ischemia and reflow. However, our investigations have shown that massive thiol oxidation and lipid peroxidation are not observed in the rat liver or in the canine heart models of ischemia and reflow. We are proposing, therefore, that the reactive oxygen species may be enhancing tissue damage through modulation of the activities of lipoxygenases and hence the formation of the chemotactic and vasoactive eicosanoid metabolites. Obviously, an understanding of the mechanisms involved in reperfusion injury is extremely important, particularly in view of the increasing use of cardiac interventions such as thrombolytic therapy and/or precutaneous transluminal coronary angioplasty. The increasing clinical use of organ transplantation further emphasizes the need to identify the mechanisms of reprefusion injury.
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