Objectives: The purpose of this study was to test the hypothesis that free oxygen radicals contribute to platelet aggregation and cyclic flow variations in stenosed and endothelium-injured coronary arteries.
Background: Although free oxygen radicals, such as superoxide anion and hydrogen peroxide, have been shown to alter platelet function in vitro, the potential role of free oxygen radicals has not been fully described in an in vivo model of coronary artery thrombosis.
Methods: Cyclic flow variations were produced in dogs by an external constrictor placed at the site of the left anterior descending coronary artery with injured endothelium. Blood flow in this artery was monitored by a pulsed Doppler flow probe. If cyclic flow variations were observed during postoperative days, dogs intravenously received superoxide dismutase plus catalase. In anesthetized dogs that did not develop an episode of cyclic flow variations, the effect of intracoronary infusion of xanthine plus xanthine oxidase or hydrogen peroxide on arterial blood flow velocity was studied. In platelet studies, the effect of free oxygen radicals and radical scavengers on platelet aggregation was examined.
Results: In conscious dogs with cyclic flow variations, superoxide dismutase plus catalase significantly reduced cyclic flow variations (n = 7), whereas saline infusion had no effect (n = 7). The infusion of xanthine plus xanthine oxidase or hydrogen peroxide significantly induced cyclic flow variations in four of six dogs or in five of seven dogs, respectively. In vitro platelet studies showed that xanthine plus xanthine oxidase or hydrogen peroxide significantly enhanced platelet aggregation, and superoxide dismutase or catalase significantly inhibited such aggregation.
Conclusions: Reduction of free radical formation decreases platelet aggregation and may eliminate cyclic flow variations, whereas promotion of free radical generation enhances platelet aggregation and may induce cyclic flow variations. Thus, free oxygen radicals are an important mediator in this model.