ObjectiveTo 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.DesignProspective and randomized.SettingAnimal research facility.SubjectsMale Sprague-Dawley rats.InterventionsRats underwent pressure-controlled (mean arterial pressure 40 mm Hg) hemorrhagic shock for 90 mins. They were randomized to normothermia (38.0 ± 0.5°C) or mild hypothermia (33–34°C from hemorrhagic shock 20 mins to resuscitation time 12 hrs). Rats were killed at resuscitation time 3 or 24 hrs.Measurements and Main ResultsAll 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&bgr;, interleukin-6, and tumor necrosis factor-&agr; peaked at resuscitation time 1 hr. Tumor necrosis factor-&agr; 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).ConclusionsThese 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.