Production of free radicals and lipid peroxides in early experimental myocardial ischemia.
Free radicals and lipid peroxides have recently been identified by us [1, 2, 3] as metabolic intermediates during acute myocardial ischemia. The mechanisms by which evolving myocardial ischemia initiates free radical production are not clear. Based on studies in vitro, it is feasible to consider the following possibilities: (a) dissociation of intramitochondrial electron support system and altered phospholipid integrity with inactivation of cytochrome oxidase, which results in release of ubisemiquinone, flavoprotein and superoxide radicals; (b) accumulation and increased release of intra/extracellular metabolites like NADH, lactate flavoproteins and catecholamines which react either with themselves or with O2 and ascorbic acid; (c) interaction of the metabolic product hypoxanthine with O2 in the presence of xanthine oxidase and (d) activation of phospholipase by calcium influx with enhanced arachidonic acid metabolism and superoxide radical production. Detailed in vitro radiobiological studies [4] have demonstrated that free radical reactions occur even at very low O2 tensions (83% of maximum rate of PO2 approximately 6 mmHg and 50% at PO2 approximately 1 mmHg), and Smith [5] has demonstrated that free radical peroxidation takes place quite rapidly in rat brain homogenates incubated in gas mixtures containing only 5% O2. Thus, the low oxygen tensions in ischemic tissue are adequate to support free radical reactions. The free radicals thus produced may initiate and enhance lipid peroxidation by attacking polyunsaturated membrane lipids.
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D003327:Coronary Disease / Q000378:metabolism*; D004285:Dogs; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000378:metabolism; D007700:Kinetics; D008054:Lipid Peroxides / Q000096:biosynthesis*; D008315:Malondialdehyde / Q000378:metabolism; D010084:Oxidation-Reduction
D002395:Catecholamines; D005609:Free Radicals; D008054:Lipid Peroxides; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D001205:Ascorbic Acid