GASTRIC EPITHELIAL DAMAGE-INDUCED BY LOCAL ISCHEMIA-REPERFUSION WITH OR WITHOUT EXOGENOUS ACID

We evaluated the damage to the gastric epithelium produced by local ischemia-reperfusion (IR) with or without luminal perfusion with 0.1 N HCl. Local gastric ischemia was induced by clamping the left gastric artery. Use of radioactive microsphere technique revealed a significant reduction in blood flow induced only in the corpus (67% reduction). Because no measurable gross lesion was observed in this model, the blood-to-lumen clearance of Cr-51-labeled EDTA (Cr-51-EDTA) served as an index of epithelial damage. In the absence of exogenous acid, the histological damage was minimum and could not be quantified. However, a significant increase in Cr-51-EDTA clearance was observed shortly after reperfusion in a manner that depended on the duration of ischemia. This increase in clearance reached a maximum similar to 10 min after reperfusion and returned rapidly toward control levels within 40-50 min after reperfusion. In the presence of exogenous acid, EDTA clearance increased significantly during ischemia, increased further during reperfusion, and did not recover for at least 60 min after reperfusion. The acid infused after reperfusion (no acid before reperfusion) did not significantly aggravate the mucosal damage that followed reperfusion. However, the acid infused before reperfusion (no acid after reperfusion) showed an effect on EDTA clearance similar to that induced by continuous acid perfusion. Allopurinol (50 mg.kg(-1).day(-1) for 2 days), superoxide dismutase (15,000 U/kg), and dimethyl sulfoxide (20 mg/kg) significantly attenuated the increase in Cr-51-EDTA clearance produced by IR without the perfusion of acid but not that produced with acid perfusion. These findings suggest that 1) local IR stress produces gastric epithelial damage immediately after reperfusion by oxygen radicals derived from the xanthine-xanthine oxidase system; 2) the gastric damage was rapidly healed in a manner consistent with restitution; 3) in the IR injury induced with exogenous luminal HCl, the acid given during the ischemia, not the oxygen radicals, plays a major role; and 4) the restitution mechanism does not reverse the epithelial damage induced by IR in the presence of exogenous HCl.