Effect of oxygen-derived free radical scavengers on infarct size following six hours of permanent coronary artery occlusion: salvage or delay of myocyte necrosis?

Abstract

Oxygen-derived free radicals (O ₂ ⁻ and ·OH) have been implicated in myocardial injury associated with coronary artery occlusion followed by reperfusion. While these cytotoxic oxygen species are predominantly produced upon reintroduction of molecular oxygen to previously ischemic tissue, they may also be generatedthroughout coronary occlusion in species (such, as dog and man) in which native collateral vessels permit residual blood flow into the ischemic bed. To test this theory, 20 anesthetized, open-chest dogs underwent 6 h of permanent left anterior descending coronary artery occlusion: ten dogs were treated with the potent free radical scavenging enzymes superoxide dismutase (SOD: 5 mg/kg per hour) plus catalase (5 mg/kg per hour), while the remaining ten animals received saline. Infusion of drug or saline solution was begun 15 min prior to occlusion, and maintained throughout occlusion. Infusion of SOD+catalase did not significantly affect the extent of the area at risk of infarction (19.5±1.8% vs 24.0±1.4% of the left ventricle for the treated vs control group;P=NS), did not reduce myocardial oxygen demand (heart rate and arterial pressures were comparable for both groups), and did not alter collateral blood flow to the ischemic myocardium. However, mean infarct size in dogs treated with SOD+catalase (39.6±6.6% of the area at risk; 8.4±2.1% of the left ventricle) was significantly smaller than that observed in the saline controls (73.0±6.3% of the area at risk,PPP=NS). These results suggest that infusion of SOD+catalase in this model may delay, but not prevent, the development of ischemic necrosis.