Cardiovascular Membranes as Models for the Study of Free Radical Injury

Abstract

Following ischemia — a condition characterized by oxygen depletion, acidosis, and retention of tissue metabolites (1) — severe oxidative damage to cardiovascular tissues occurs upon reperfusion. However, early reperfusion remains the major clinical method to salvage ischemic myocardium and further elucidation of the multiple injury mechanisms operative during ischemia/reperfusion is necessary to solve this paradoxical dilemma. In the process of ischemia/reperfusion, mounting evidence has confirmed that the generation of oxygen-derived free radicals participates in the injury process (2–4). At the whole organ level, the reported protection of cardiovascular tissues by antioxidant-type enzymes (eg. superoxide dismutase and catalase), antioxidant drugs (eg. deferoxamine) and vitamins (eg. vitamin E) suggest a role for free radicals in the reperfusion injury. In recent years studies employing electron spin resonance spectroscopy and spin-trapping agents have shown that increased production of free radicals occurs during ischemia and myocardial reperfusion (4–11). The specific cellular sites of generation of these toxic free radicals are not known. Certainly white cells migrating into ischemic/reperfused areas of myocardium are capable of generating significant amounts of superoxide anions (2,12–14); endothelial cells (15–17) and cardiomyocytes (18) have been reported to generate oxygen-derived free radicals as well. Nevertheless, the relative contribution of each of the various cell types to the overall process of injury of cardiovascular tissues remains an area of intense investigation. One significant challenge for this area of investigation is whether or not sufficient radicals accumulate to overwhelm the intrinsic cellular protective mechanisms.KeywordsCardiovascular TissueHydroxyl Free RadicalLinoleate HydroperoxidePalmitoyl CarnitineFree Radical InjuryThese 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.