Reperfusion injury.
Several lines of evidence point to a major role of oxygen free radicals in the pathogenesis of cell death or dysfunction in a variety of disease processes. Recent studies from this as well as other laboratories have demonstrated that oxygen free radicals play a major role in the pathogenesis of post-ischemic reperfusion injury in the heart. We have recently developed methods for direct measurement of radical species and/or specific byproducts of radical injury. Timely administration of oxygen radical scavengers reduced the quantity of free radicals generated following reperfusion and in addition improved recovery of post-ischemic ventricular function and metabolism. In a regionally ischemic model the free radical scavenger recombinant human superoxide dismutase also administered at the time of reflow was shown to limit infarct size. In this article we review the biophysical and molecular mechanisms of oxygen free radical generation that are viewed as contributing to post-ischemic reperfusion injury. We also discuss the mechanisms by which the body defends against free radical attack and the interrelationships of free radical injury to other mechanisms of tissue injury.
Flaherty
J T
JT
Department of Medicine, Johns Hopkins Hospital, Clayton Heart Center, Baltimore, MD 21205.
Weisfeldt
M L
ML
D000818:Animals; D000975:Antioxidants; D006348:Cardiac Surgical Procedures / Q000009:adverse effects; D002374:Catalase / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000494:pharmacology; D006801:Humans; D007962:Leukocytes / Q000201:enzymology; D008929:Mitochondria, Heart / Q000201:enzymology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology; D010085:Oxidative Phosphorylation; D010100:Oxygen / Q000378:metabolism; D011453:Prostaglandins / Q000096:biosynthesis; D011817:Rabbits; D015427:Reperfusion Injury / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D000975:Antioxidants; D002395:Catecholamines; D005609:Free Radicals; D011453:Prostaglandins; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D010100:Oxygen