Sequence of gastric mucosal injury following ischemia and reperfusion. Role of reactive oxygen metabolites.

The mechanisms of gastric mucosal injury following a period of ischemia remain unclear. The aim of this study was to determine the relative contributions of ischemia, reperfusion, and reactive oxygen metabolites to mucosal injury induced by temporary occlusion of the celiac artery. Rats were subjected to 30 min of gastric ischemia in the presence of 100 mM HCl. Reperfusion periods ranged from 1 min to 24 hr. Drug treatments included allopurinol (100 mg/kg) or a combination of superoxide dismutase (15,000 units/kg), catalase (90,000 units/kg), and desferrioxamine (50 mg/kg). Mucosal injury was assessed by quantitative histology and the extent of macroscopic hemorrhage. Approximately one third of the total injury to the volume of the mucosa (11.8 +/- 9.1%) was due to ischemia alone. Another third was blocked by allopurinol or superoxide dismutase, catalase, and desferrioxamine (22.1 +/- 6.9%, P less than 0.001; and 25.9 +/- 4.6%, P less than 0.01), respectively, compared with control (32.5 +/- 5.1%). In contrast, extensive surface mucosal injury (62.2 +/- 27.6%) occurred primarily during ischemia and was not affected by antioxidants. Macroscopic hemorrhage was halved by treatment with allopurinol (17.5 +/- 12.6%, P less than 0.01) or superoxide dismutase, catalase, and desferrioxamine (15.9 +/- 14.5%, P less than 0.01). We conclude that temporary celiac occlusion results in gastric mucosal damage that consists of both ischemic and reperfusion components. The majority of surface mucosal injury occurred during ischemia, whereas injury to the volume of the mucosa and the vasculature occurred equally during reperfusion and was associated with reactive oxygen metabolites.