title: Mild hypothermia during hemorrhagic shock in rats improves survival without significant effects on inflammatory responses.
abstract: OBJECTIVE
  To explore the hypothesis that the survival benefit of mild, therapeutic hypothermia during hemorrhagic shock is associated with inhibition of lipid peroxidation and the acute inflammatory response.
  
  
  METHODS
  Prospective and randomized.
  
  
  METHODS
  Animal research facility.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  Rats underwent pressure-controlled (mean arterial pressure 40 mm Hg) hemorrhagic shock for 90 mins. They were randomized to normothermia (38.0 +/- 0.5 degrees C) or mild hypothermia (33-34 degrees C from hemorrhagic shock 20 mins to resuscitation time 12 hrs). Rats were killed at resuscitation time 3 or 24 hrs.
  
  
  RESULTS
  All seven rats in the hypothermia group and seven of 15 rats in the normothermia group survived to 24 hrs (p <.05). Hypothermic rats had lower serum potassium and higher blood glucose concentrations at 90 mins of hemorrhagic shock (p <.05). At resuscitation time 24 hrs, the hypothermia group had less liver injury (based on serum concentrations of ornithine carbamolytransferase and liver histology) and higher blood glucose than the normothermia group (p <.05). There were no differences in serum free 8-isoprostane (a marker of lipid peroxidation by free radicals) between the two groups at either baseline or resuscitation time 1 hr. Serum concentrations of interleukin- 1 beta, interleukin-6, and tumor necrosis factor-alpha peaked at resuscitation time 1 hr. Tumor necrosis factor-alpha concentrations were higher (p <.05) at resuscitation time 1 hr in the hypothermia group compared with the normothermic group. Serum cytokine concentrations were not different between survivors and nonsurvivors in the normothermia group. Serum cytokine concentrations returned to baseline values in both groups by 24 hrs. There were no differences in the number of neutrophils in the lungs or the small intestine between the groups. More neutrophils were found in the lungs at resuscitation time 3 hrs than at resuscitation time 24 hrs in both groups (p <.01).
  
  
  CONCLUSIONS
  These data suggest that lipid peroxidation and systemic inflammatory responses to hemorrhagic shock are minimally influenced by mild hypothermia, although liver injury is mitigated and survival improved. Other mechanisms of benefit from mild hypothermia need to be explored.
authors.affiliation: Department of Critical Care Medicine, Safar Center for Resuscitation Research, University of Pittsburgh, PA, USA.
authors.forename: Xianren
authors.initials: X
authors.lastname: Wu
authors.forename: Jason
authors.initials: J
authors.lastname: Stezoski
authors.forename: Peter
authors.initials: P
authors.lastname: Safar
authors.forename: Anthony
authors.initials: A
authors.lastname: Bauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Tuerler
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schwarz
authors.forename: Rainer
authors.initials: R
authors.lastname: Kentner
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Behringer
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: Samuel A
authors.initials: SA
authors.lastname: Tisherman
mesh_terms: D000818:Animals; D007036:Hypothermia, Induced; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D015227:Lipid Peroxidation; D008099:Liver / Q000473:pathology; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000628:therapy*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D015850:Interleukin-6; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha