Xanthine Oxidase is not Likely to be a Source of Injurious Free Radicals in the Ischemic Human Heart: A Study of Species Differences

Abstract

Oxygen derived free radicals appear to contribute to ischemia-reperfusion injury in the heart (1,2). The source of these radicals, however, remains a subject of current debate. Studies from this laboratory indicate that xanthine oxidase is an important source of cytotoxic free radicals in the reperfused dog heart (3). Xanthine oxidase can produce oxi-radicals by the following mechanism. During ischemia ATP in the myocyte is degraded through several intermediates to hypoxanthine (4) which is the substrate for cardiac xanthine oxidase. This enzyme, which is thought to reside exclusively in the coronary capillary endothelium (5), oxidizes hypoxanthine to urate. An important feature of the xanthine oxidase hypothesis is the conversion of xanthine dehydrogenase to xanthine oxidase. The enzyme is thought to exist primarily as a dehydrogenase in normal myocardium and in this state it can only use NAD+ as the electron acceptor during the oxidation of purines (6,7). Thirty minutes of ischemia in the dog heart caused about 30% of the enzyme to be converted to the oxidase form (3) which can utilize molecular oxygen as an electron acceptor, reducing that oxygen to Superoxide and hydrogen peroxide (8).KeywordsInfarct SizeXanthine OxidaseRabbit HeartXanthine Oxidase ActivityXanthine DehydrogenaseThese 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.