Myocardial malondialdehyde and uric acid release after short-lasting coronary occlusions during coronary angioplasty: Potential mechanisms for free radical generation

The stunned myocardium has recently become the focus of considerable interest because of its potential role in negating the benefits of reperfusion. A critical but still unresolved issue relates to the mechanism responsible for this contractile abnormality. In recent years an increasing number of studies have provided indirect evidence that postischemic myocardial dysfunction may be mediated in part by the generation of reactive oxygen species, such as superoxide radical, hydrogen peroxide and hydroxyl radical. These oxygen-free radicals could arise from various sources, such as hypoxanthine conversion by xanthine oxidase, catecholamine degradation and mitochondrial electron transport. Direct evidence of injury by free radicals has yet to be shown in the human heart, but many studies of other mammals have linked reactive oxygen metabolites with myocardial injury.1–5 During myocardial ischemia, xanthine dehydrogenase (which appears to be located in the endothelial cells)6 is converted to xanthine oxidase, an enzyme that produces superoxide radical, hydrogen peroxide and uric acid from hypoxanthine or xanthine and molecular oxygen.7 At the same time, ischemia is associated with rapid catabolism of adenosine triphosphate.7 This degradation of adenosine triphosphate causes an efflux of breakdown products that are able to pass through the cell membrane, resulting in an accumulation of hypoxanthine, 1 of 2 substrates for xanthine oxidase. The other substrate (molecular oxygen) is provided by reperfusion, which results in a burst of free-radical generation. 8 These free radicals initiate chain reactions causing peroxidative breakdown of polyunsaturated fatty acids in the membrane bilayer.9–12 The interaction among oxygen-free radicals with polyunsaturated fatty acids has been described as lipid peroxidation and can be measured by formation of malondialdehyde. Until recently, the assessment of alterations in myocardial metabolism in humans early after short and repetitive occlusions of a major coronary artery has not been feasible. However, percutaneous transluminal coronary angioplasty provides a unique opportunity to study the time course of these metabolic changes during transient interruption of coronary flow by the balloon-occlusion sequence in patients with 1-vessel disease and without angiographically demonstrable collateral circulation.13–16 In this report we studied the production of hypoxanthine, urate and malondialdehyde during percutaneous transluminal coronary angioplasty.