title: Conventional dose hypertonic saline provides optimal gut protection and limits remote organ injury after gut ischemia reperfusion.
abstract: BACKGROUND
  Hypertonic saline (HS) resuscitation prevents neutrophil mediated injury after shock. The optimal dose is not known, but appears as a result of osmotic stress. We hypothesized that a dose dependent effect exists related to increasing tonicity and that the optimal gut protective dose would provide better protection against remote organ injury than large volume isotonic crystalloids.
  
  
  METHODS
  In experiment 1, rats were assigned to controls (sham/no resuscitation, sham/4 mL/kg 7.5% HS, superior mesenteric artery occlusion [SMAO]/no resuscitation), SMAO/equal volume (4 mL/kg 0.9% NS, 4 mL/kg 2.5% HS, 4 mL/kg 5% HS, 4 mL/kg 7.5% HS and 4 mL/kg 10% HS) or SMAO/equal sodium (33 mL/kg 0.9% NS, 12 mL/kg 2.5% HS, 6 mL/kg 5% HS, 4 mL/kg 7.5% HS, and 3 mL/kg 10% HS). In experiment 2, rats were assigned to the same control groups, and to either SMAO/NS (33 mL/kg 0.9% NS, equal salt load) or SMAO/HS (4 mL/kg 7.5% HS). The SMAO was clamped for 60 minutes and boluses given 5 minutes before clamp removal. After 6 hours of reperfusion, ileum and lungs were harvested for analysis of histologic injury, myeloperoxidase (MPO) as an index of neutrophil mediated injury, and serum ALT and AST drawn as markers of liver injury.
  
  
  RESULTS
  In experiment 1, equal volume and equal sodium decreased injury and inflammation with increasing tonicity in a dose dependent fashion, with the optimal effect seen at 7.5%. In experiment 2, NS resuscitation resulted in minimal improvement of SMAO-induced lung injury and inflammation or increases in serum ALT and AST whereas HS resuscitation significantly decreased these parameters.
  
  
  CONCLUSIONS
  The protective effect of HS is related to increased tonicity. While NS had little effect on SMAO-induced remote organ injury, optimal dose HS resuscitation was quite protective. This supports the growing evidence that HS protection may be because of its gut protective effects.
authors.affiliation: Department of Surgery, The University of Texas Medical School at Houston, Houston, Texas 77030, USA. Ernest.A.Gonzalez@uth.tmc.edu
authors.forename: Ernest A
authors.initials: EA
authors.lastname: Gonzalez
authors.forename: Rosemary A
authors.initials: RA
authors.lastname: Kozar
authors.forename: James W
authors.initials: JW
authors.lastname: Suliburk
authors.forename: Norman W
authors.initials: NW
authors.lastname: Weisbrodt
authors.forename: David W
authors.initials: DW
authors.lastname: Mercer
authors.forename: Frederick A
authors.initials: FA
authors.lastname: Moore
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000077324:Crystalloid Solutions; D004305:Dose-Response Relationship, Drug; D005440:Fluid Therapy / Q000379:methods*; D007082:Ileum / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007552:Isotonic Solutions / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage / Q000494:pharmacology*; D012771:Shock, Hemorrhagic / Q000628:therapy*; D013152:Splanchnic Circulation / Q000187:drug effects*
chemical_list: D000077324:Crystalloid Solutions; D007552:Isotonic Solutions; D012462:Saline Solution, Hypertonic