Hypothermia protects against gut ischemia/reperfusion-induced impaired intestinal transit by inducing heme oxygenase-1

Bashir O. Attuwaybi, Heitham T. Hassoun, Lei Zou, Rosemary A. Kozar, Bruce C. Kone, Norman W. Weisbrodt, Frederick A. Moore

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose. Gut 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-κB 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 methods. At 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°C). Each animal was placed on a heating blanket maintaining systemic normothermia (37°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 μmol/kg, ip), 1 h before superior mesenteric artery occlusion and transit measured as above. Results. Rats 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. Conclusion. We 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.

Original languageEnglish (US)
Pages (from-to)48-55
Number of pages8
JournalJournal of Surgical Research
Volume115
Issue number1
DOIs
StatePublished - Nov 2003

Keywords

  • HO-1
  • Ileus
  • Ischemia/reperfusion
  • MOF
  • TAAA
  • iNOS

ASJC Scopus subject areas

  • Surgery

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