GUT ISCHEMIA: OXYGEN DELIVERY AND SUPEROXIDE RADICALS

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The mortality rate from intestinal ischemia is near 100% and accounts for 3% of the deaths in this country. Considerable attention has been directed to improvement of intestinal blood flow with vasodilator drugs. However, the contribution of low flow, per se, as distinct from hypoxia to mucosal injury has not been clearly demonstrated. Accordingly, we propose to investigate the roles of oxygen delivery and blood flow in the genesis of mucosal injury in isolated segments of canine ileum. Four series of experiments will be conducted. Perfusion with venous blood with high and low oxygen content will be contrasted with arterial blood perfusion at normal flow levels. Low flow perfusion with arterial blood will be combined with luminal perfusion with normal physiological saline, with a glucose load to stimulate metabolism and with a fluorocarbon emulsion to enhance oxygen delivery. Low flow perfusion effects of arterial blood containing either fluorocarbon emulsion or inositol hexaphosphate treated erythrocytes to enhance vascular oxygen delivery will be determined. The effects of added intrarterial vasodilators will be determined during low pressure and low flow perfusion. Vascular resistance will be used as an index of the local circulatory responses. Blood flow distribution between mucosal/submucosal and muscularis regions of each intestinal segment will be determined by radionuclide microspheres. Serial tissue samples will be analyzed for ATP, xanthine, hypoxanthine, uric acid, inorganic phosphate, lactate/pyruvate ratio, glutamate-oxaloacetate transaminase, citrate synthase, Beta-glucuronidase and malondialdehyde to estimate the involvement of cytotoxic oxygen radicals in the morphologic alterations associated with ischemia. Light, scanning, and transmission electron microscopy will document morphologic changes and scanning, and transmission electron microscopy will document morphologic changes and scanning, and transmission electron microscopy will document morphologic changes and the time course of the cellular events. The results of these studies will provide new insights of the causative factors which precipitate the fatal consequences of circulatory insufficiency in the intestine.