title: Hypertonic saline prevents inflammation, injury, and impaired intestinal transit after gut ischemia/reperfusion by inducing heme oxygenase 1 enzyme.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, University of Texas-Houston, Houston, Texas 77030, USA.
authors.forename: Bashir
authors.initials: B
authors.lastname: Attuwaybi
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Kozar
authors.forename: Keith S
authors.initials: KS
authors.lastname: Gates
authors.forename: Stacey
authors.initials: S
authors.lastname: Moore-Olufemi
authors.forename: Norio
authors.initials: N
authors.lastname: Sato
authors.forename: Norman W
authors.initials: NW
authors.lastname: Weisbrodt
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Moore
mesh_terms: D000818:Animals; D004790:Enzyme Induction / Q000187:drug effects*; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis* / Q000378:metabolism; D051547:Heme Oxygenase-1; D007249:Inflammation / Q000517:prevention & control*; D007413:Intestinal Mucosa / Q000187:drug effects / Q000293:injuries; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D012151:Resuscitation / Q000379:methods; D012462:Saline Solution, Hypertonic / Q000627:therapeutic use*; D012769:Shock / Q000201:enzymology / Q000378:metabolism / Q000628:therapy
chemical_list: D012462:Saline Solution, Hypertonic; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1