Hypertonic Saline Prevents Inflammation, Injury, and Impaired Intestinal Transit after Gut Ischemia/Reperfusion by Inducing Heme Oxygenase 1 Enzyme

Bashir Attuwaybi, Rosemary A. Kozar, Keith S. Gates, Stacey Moore-Olufemi, Norio Sato, Norman W. Weisbrodt, Frederick A. Moore, Robert N. Cooney, Henri Ford, Eriq Barquist

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Abstract

Background: Hypertonic saline (HTS) has been shown to modulate the inflammatory response after shock. We have previously demonstrated that heme oygenase-1 (HO-1) induction is protective against gut dysfunction in models of shock-induced gut ischemia/reperfusion (I/R). We therefore hypothesized that HTS prevents gut inflammation, injury, and impaired transit by inducing HO-1 in a model of gut I/R. Methods: Rats underwent 60 minutes of superior mesenteric artery occlusion (SMAO) and then were resuscitated with 4 mL/kg of HTS, an equal volume of lactated Ringer's (LR) solution (4 mL/kg, low volume), or equal salt LR solution (32 mL/kg, high volume) and compared with SMAO alone or shams. A separate group was pretreated with the HO-1 blocker Sn protoporphyrin IX (SNP IX) before SMAO plus HTS. At 6 hours of reperfusion, transit was determined and ileum harvested for HO-1 (anti-inflammatory) and inducible nitric oxide synthase (proinflammatory) immunoreactivity, myeloperoxidase (MPO) activity, and histologic injury. Data are expressed as mean ± SEM (analysis of variance). Results: Intestinal transit was severely impaired after SMAO (2.5 ± 0.1), improved with low- and high-volume LR solution (3.2 ± 0.2 and 3.1 ± 0.1, not significant), but returned to sham (4.6 ± 0.2) with HTS (4.8 ± 0.2). Pretreatment with SNP abrogated this protective effect. Myeloperoxidase activity was significantly increased by SMAO (SMAO, 2.3 ± 0.3; sham, 0.4 ± 0.05), lessened by low- and high-volume LR solution (1.5 ± 0.3 and 1.7 ± 0.4), but returned to sham levels with HTS (1.0 ± 0.01). Activity with SNP IX pretreatment was significantly increased (4.04 ± 0.8). Mucosal injury followed a similar pattern. Inducible nitric oxide synthase was increased by SMAO and low- and high-volume LR solution (0.8 ± 0.2, 0.8 ± 0.03, and 0.8 ± 0.02, respectively; sham, 0.5 ± 0.02), but significantly reduced by HTS (0.7 ± 0.02). HO-1 was induced by SMAO and low-and high-volume LR solution (0.33 ± 0.02, 0.32 ± 0.03, and 0.37 ± 0.4, respectively; sham, 0.0 ± 0.0), but was further increased with HTS (0.49 ± 0.04). Conclusion: HTS resuscitation protects against inflammation, injury, and impaired intestinal transit after gut I/R in part by inducing HO-1. This is a novel mechanism of HO-1 protection.

Original languageEnglish (US)
Pages (from-to)749-759
Number of pages11
JournalJournal of Trauma - Injury, Infection and Critical Care
Volume56
Issue number4
DOIs
StatePublished - Jan 1 2004
Externally publishedYes

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Keywords

  • Heme oxygenase-1
  • Hypertonic saline
  • Inducible nitric oxide synthase (iNOS)
  • Intestinal transit
  • Ischemia/reperfusion

ASJC Scopus subject areas

  • Surgery
  • Critical Care and Intensive Care Medicine

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