Abstract
Under normal conditions the intestinal mucosa is impermeable to potentially harmful materials from the intestinal lumen. Mucosal disruption promotes bacterial translocation, which is postulated to be a fuel source for sepsis and multiorgan failure. We have previously demonstrated that mesenteric ischemia-reperfusion ( I R ) injury increases intestinal permeability (IP); however, the mechanism remains unclear. This study was designed to examine the hypothesis that changes in IP, after I R injury, are mediated by xanthine oxidase-generated, oxygen-derived free radicals. Thirty-three Sprague-Dawley rats (weighing 300 to 400 g) were included in this study. Group 1 (n = 10) received enteral allopurinol, a xanthine oxidase inhibitor, 10 mg/kg daily for 1 week prior to mesenteric ischemia. Group 2 consisted of 11 untreated, ischemic animals. Groups 1 and 2 were subjected to superior mesenteric artery occlusion with interruption of collateral flow for 20 minutes to produce ischemic injury to the intestine. An additional 12 rats (group 3), served as nonischemic controls (sham). A loop of distal ileum was isolated and cannulated proximally and distally to allow luminal perfusion with warmed Riinger's lactase at 1 mL/min. IP was determined in all groups by quantitatively measuring the plasma-to-luminal clearance of chromium ( 51Cr)-labeled ethylenediaminetetraacetate (EDTA) at baseline, during ischemia and 20, 40, and 60 minutes after reperfusion. Complete ischemia produced significant increases in IP over baseline values in the untreated rats (group 2, baseline: 0.49 ± 0.006, ischemia: 0.149 ± 0.039) compared with sham rats (baseline: 0.41 ± 0.006; ischemia; 0.047 ± 0.009) or allopurinol-treated rats (baseline: 0.098 ± 0.020, ischemia: 0.073 ± 0.012, P < .001). IP in allopurinol-treated rats remained unchanged 60 minutes postreperfusion (0.098 ± 0.024) whereas 60 minutes of reperfusion produced significant increases in IP in untreated rats (0.196 ± 0.049). We conclude that enteral allopurinol exerts a protective effect on the intestinal mucosa, preventing permeability changes in response to I R injury. In addition, these data suggest that oxygen-derived free radicals contribute to I R - mediated increases in IP.
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