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- Bashir O Attuwaybi, Heitham T Hassoun, Lei Zou, Rosemary A Kozar, Bruce C Kone, Norman W Weisbrodt, and Frederick A Moore.
- Department of Surgery, Trauma Research Center, University of Texas-Houston Medical School, Houston, Texas, USA.
- J. Surg. Res. 2003 Nov 1; 115 (1): 48-55.
PurposeGut ischemia/reperfusion (I/R) elicits an inflammatory response that impairs intestinal transit. We have previously shown that regional intraischemic hypothermia (IH) protects against moderate gut I/R-induced mucosal injury, is associated with decreased NF-kappaB activity and inducible nitric oxide synthase induction and preserves heme oxygenase-1 (HO-1) expression. HO-1 provides cytoprotection in various models of oxidant stress. We, therefore, tested the hypothesis that IH protects against gut I/R-induced impaired intestinal transit via HO-1 induction.Materials And MethodsAt laparotomy (lap), Sprague-Dawley rats had duodenal catheters placed followed by sham or gut I/R (superior mesenteric artery occlusion for 75 min) with or without regional IH (15 degrees C). Each animal was placed on a heating blanket maintaining systemic normothermia (37 degrees C). At 12 or 24 h of reperfusion, small intestinal transit was determined by quantitating the distribution of a tracer (FITC dextran) in the intestine 30 min after instillation (expressed as geometric center of distribution). Ileal samples were obtained for histology and HO-1 expression, assessed by Western immunoblot at 12 and 24 h of reperfusion. In separate experiments, rats were pretreated with an HO-1 inhibitor Sn protoporphyrin IX (25 mumol/kg, ip), 1 h before superior mesenteric artery occlusion and transit measured as above.ResultsRats treated with I/R had increased histological injury and impaired intestinal transit at both 12 and 24 h compared with sham. Rats treated with I/R+IH exhibited histological injury and transit comparable with sham controls. I/R induced HO-1 expression at 12 and 24 h of reperfusion and IH augmented this I/R-induced HO-1 expression. Sn protoporphyrin IX abrogated IH protection against histological injury and impaired transit.ConclusionWe conclude that intraischemic regional hypothermia protects against histological injury and impaired intestinal transit caused by severe gut I/R injury. Hypothermic protection under these conditions is in part due to HO-1 expression.
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