ISCHEMIA-REPERFUSION INJURY IN THE INTESTINES OF NEWBORN PIGS

Although the pathogenesis of necrotizing enterocolitis remains uncerta in, ischemia appears to be an important contributing factor to the dev elopment of this disorder. Reperfusion plays a major role in ischemia- related injury, and oxygen free radicals produced during reperfusion m ost likely contribute to the injury. These oxidants can be generated d uring prostanoid metabolism, which increases during reperfusion of isc hemic gut in adult subjects. The present study was designed to: 1) exa mine the effects of superior mesenteric artery occlusion, e.g. ischemi a and reperfusion in vivo on the development of histopathologic intest inal injury; 2) determine whether products of arachidonic acid metabol ism, e.g. prostanoids are increased during reperfusion of ischemic gut ; and 3) determine whether oxygen free radical scavengers attenuate th e injury in newborn pigs. Chronically catheterized placebo-pretreated newborn pigs exposed to ischemia-reperfusion, placebo-pretreated nonis chemic control pigs, and polyethylene glycol-superoxide dismutase (SOD ) plus polyethylene glycol-catalase (CAT)-pretreated, ischemic pigs we re studied by examining changes in intestinal circulation, oxygenation , prostanoids, and tissue injury. In the placebo-pretreated pigs, inte stinal blood flow decreased to very low levels during superior mesente ric artery occlusion. During reperfusion, blood flow increased, but re mained below baseline. After ischemia, oxygen uptake returned to value s that were similar to baseline. Intestinal efflux of the vasodilator 6-keto-prostaglandin F-1 alpha was evident (p < 0.05 versus no or zero efflux) during early reperfusion. Histopathologic scoring of terminal ileal samples showed significant mucosal necrosis, surface epithelial disruption, lamina propria congestion and hemorrhage, submucosal hemo rrhage, edema, and increases in cells compared with the placebo-pretre ated nonischemic pigs. In the SOD plus CAT-pretreated ischemic pigs, c hanges in intestinal blood flow, oxygen uptake, 6-keto-prostaglandin F -1 alpha efflux, and the pattern of the ileal tissue injury did not di ffer significantly from the placebo-pretreated ischemic pigs. In summa ry, superior mesenteric artery occlusion for 1 h and reperfusion for 2 h resulted in severe intestinal ischemia, early postocclusive limited increases in intestinal perfusion and oxygen uptake, efflux of vasodi lating prostanoids during early reperfusion, and signs of ischemic tis sue injury in the placebo- and SOD plus CAT-pretreated pigs. This stud y demonstrates that, after superior mesenteric artery occlusion and re perfusion, severe intestinal tissue injury is detected in vivo, prosta noid efflux increases, and SOD plus CAT given just before occlusion do es not attenuate the extent of injury in newborn pigs.