Sequence of gastric mucosal injury following ischemia and reperfusion

Abstract

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.

Involvement of superoxide and xanthine oxidase in neutrophil‐independent rat gastric damage induced by NO donors

“…Allopurinol, administered by acute pretreatment by the intraperitoneal route, or following oral administration over 2 days, reduced the mucosal injury induced by local infusion nitroprusside or SNAP. As with the protective actions of allopurinol on gastric mucosal injury following hypovolaemic shock in the gastric mucosa and ischaemia reperfusion in the stomach and intestine (Granger et al, 1981;Itoh & Guth, 1985;Perry et al, 1986;Andrews et al, 1992), such actions should reflect the inhibition of xanthine oxidase. The specificity of these actions of allopurinol in the present study was demonstrated by its failure to attenuate the mucosal injury induced by close-arterial infusion of endothelin-1.…”

Role of Nitric Oxide and Mucus in Ischemia/Reperfusion-Induced Gastric Mucosal Injury in Rats

“…NO synthesis modulators (L-arginine, 200 mg/kg or L-NAME, 10 mg/kg or L-NAME with L-arginine) were injected intraperitoneally to the rats. The doses of NO synthesis modulators were adapted from previous studies dealing with gastroprotection against necrotizing agents in rats [5,24]. Control animals received an equivalent volume of saline.…”

“…More and more evidence suggests that the majority of injuries occur during reperfusion [3][4][5], and this may be attributable to reactive oxygen metabolites initially generated at the level of the vasculature [6]. Sources of reactive oxygen metabolites in reperfusing tissues include the xanthine oxidase system, which produces superoxides and hydrogen peroxides during reperfusion [7,8], and activated neutrophils, which infiltrate into the tissues and bind to the microvascular endothelium [9,10].…”

Decay-Accelerating Factor in Guinea Pig Stomachs Following Ischemia Reperfusion Stress

“…Platelet activating factor (12,13), acidosis (14) and free radicals (15,16) have been reported to participate in mucosal injury induced by ischemia reperfusion (I/R). In our previous study, complement activation played an essential role in systemic shock following intestinal I/R (17).…”