Role of free radicals and neutrophils in canine myocardial reperfusion injury: myocardial salvage by a novel free radical scavenger, 2-octadecylascorbic acid

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Abstract
To define the role of oxygen free radicals and neutrophil involvement in evolving myocardial reperfusion injury, we evaluated the effect of 2-octadecylascorbic acid (CV-3611), a novel free radical scavenger, on neutrophil function and the extent of myocardial damage resulting from 90 min of ischaemia followed by 5 h of reperfusion in an experimental model of myocardial infarction. Dogs were randomly assigned to receive CV-3611 (5 mg·kg−1·[5 min]−1, intravenously) just before the onset of reperfusion. Infarct size, as a percent of area at risk, was reduced by 60% in CV-3611 treated group as compared with control, at 16.7(SEM 3.1)% v 41.5(4.5)%, p<0.01. Administration of CV-3611 markedly reduced function of neutrophils isolated from peripheral circulation during reperfusion ex vivo as estimated by free radical generation (ferricytochrome c reduction and luminol enhanced chemiluminescence), chemotactic activity, and aggregation induced by A23187. Under these conditions, the enhancement in neutrophil infiltration and free radical generation (luminol enhanced chemiluminescence) in myocardium within area at risk, especially in the border zone between viable and irreversible injured myocardium, was markedly reduced. Haemodynamic profiles were similar between control and CV-3611 treated group. These results suggest that activated neutrophils, especially their generation of oxygen free radicals, contribute to reperfusion induced myocardial injury.