title: HSPTX protects against hemorrhagic shock resuscitation-induced tissue injury: an attractive alternative to Ringer's lactate.
abstract: BACKGROUND
  Conventional fluid resuscitation with Ringer's lactated (RL) activates neutrophils and causes end-organ damage. We have previously shown that HSPTX, a combination of small volume hypertonic saline (HS) and pentoxifylline (PTX), a phosphodiesterase-inhibitor, downregulates in vitro neutrophil activation and proinflammatory mediator synthesis. Herein, we hypothesized that HSPTX decreases end-organ injury when compared with RL in an animal model of hemorrhagic shock.
  
  
  METHODS
  Sprague-Dawley rats were bled to a mean arterial pressure of 35 mm Hg for 1 hour. Animals were divided into 3 groups: sham (no shock, no resuscitation, n = 7), RL (32 mL/kg, n = 7), and HSPTX (7.5% NaCl 4 mL/kg + PTX 25 mg/kg; n = 7). Shed blood was infused after fluid resuscitation. Blood pressure was monitored until the end of resuscitation. Animals were sacrificed at 24 hour after resuscitation. Bronchoalveolar lavage fluid (BALF) was obtained for white cell count (total and differential) and TNF-alpha and IL-1beta levels were measured by ELISA. Lung and intestinal injury at 24 hour were evaluated by histopathology. Organ damage was graded by a pathologist and a score was created (0 = no injury; 3 = severe). Lung neutrophil infiltration was evaluated by MPO immune staining.
  
  
  RESULTS
  There were no differences in mean arterial pressure between groups. At 24 hours, BALF leukocyte count was decreased by 30% in HSPTX animals (p < 0.01). TNF-alpha and IL-1beta levels were markedly decreased in HSPTX-resuscitated animals compared with their RL counterparts (p < 0.01). HSPTX-resuscitated animals (lung injury score = 1.0 +/- 0.4) had markedly decreased acute lung injury compared with RL-treated animals (2.5 +/- 0.3) (p < 0.01). RL resuscitation led to a two-fold increase in lung neutrophil infiltration whereas in HSPTX-treated animals, the number of MPO + cells was similar to sham animals (p < 0.001). Intestinal injury was markedly attenuated by HSPTX (1.1 +/- 0.3) compared with RL animals (2.6 +/- 0.4) (p < 0.001).
  
  
  CONCLUSIONS
  HSPTX, a small volume resuscitation strategy with marked immunomodulatory potential led to a marked decrease in end-organ damage. HSPTX is an attractive alternative to RL in hemorrhagic shock resuscitation.
authors.affiliation: Department of Surgery, Division of Trauma and Surgical Critical Care, University of California San Diego School of Medicine, 200 W. Arbor Drive, San Diego, CA 92103, USA. rcoimbra@ucsd.edu
authors.forename: Raul
authors.initials: R
authors.lastname: Coimbra
authors.forename: Rafael
authors.initials: R
authors.lastname: Porcides
authors.forename: William
authors.initials: W
authors.lastname: Loomis
authors.forename: Heidi
authors.initials: H
authors.lastname: Melbostad
authors.forename: Rohan
authors.initials: R
authors.lastname: Lall
authors.forename: Jessica
authors.initials: J
authors.lastname: Deree
authors.forename: Paul
authors.initials: P
authors.lastname: Wolf
authors.forename: David B
authors.initials: DB
authors.lastname: Hoyt
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D006401:Hematologic Agents / Q000008:administration & dosage*; D007082:Ileum / Q000473:pathology*; D007552:Isotonic Solutions / Q000627:therapeutic use; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic / Q000008:administration & dosage*; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D006401:Hematologic Agents; D007552:Isotonic Solutions; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic; D009195:Peroxidase; D010431:Pentoxifylline