OTA 2005 Posters

Scientific Poster #56 Basic Science

Effects of Hypothermia and Re-warming to the Inflammatory Response in a Murine Model of Trauma: Characterization of the First and the Second Hit Impact

Frank Hildebrand, MD1 (a-AO Foundation);
Martijn van Griensven, MD, PhD1 (n); Peter Giannoudis, MD2 (n);
Christian Krettek, MD1 (n); Hans-Christoph Pape, MD1 (a-AO Foundation);
1Trauma Department, Hannover Medical School, Germany;
2Department of Trauma, St. James University Hospital, Leeds, United Kingdom

Introduction: Hypothermia is a frequent event after severe trauma. Although accidental hypothermia has been identified as a major cause of posttraumatic complications, it has been suggested that it might also have beneficial effects after trauma. Therefore, this study aims to quantify the effects of hypothermia and rewarming on the inflammatory response after fracture/hemorrhage ("first hit") and subsequent fracture stabilization ("second hit").

Methods: In a two-hit mouse model, animals underwent femoral fracture (blunt guillotine device, weight of 500 g) and a standardized shock state (withdrawal of 60% of blood volume), followed by resuscitation and fixation of the fracture. Animals were sacrificed 2 hours following fixation. The four experimental groups were divided according to the time course of body temperature changes (group A, normothermia; group B, hypothermia after trauma; group C, rewarming after resuscitation; and group D, hypothermia before trauma). Groups B, C, and D were subdivided into three subgroups according to the degree of hypothermia exposed. Plasma cytokine concentrations were determined by ELISA. Pulmonary permeability changes were quantified by Bronchoalveolar Lavage. Histologic analysis of lung and liver was performed.

Results: Maintenance of normothermia resulted in a significantly decreased early survival rate (50% versus 94.7%). The degree of hypothermia, rewarming, and the time course of body temperature changes had no effect on early survival and the levels of histologic organ damage. Both a significantly increased pro- and decreased anti-inflammatory response was observed in the normothermic mice compared to hypothermia. The degree of hypothermia was associated with the extent of these observed changes with most pronounced differences in severe hypothermia. Rewarming after mild hypothermia resulted in a comparable proinflammatory response compared to normothermia.

Conclusion: Hypothermia has a beneficial effect on early survival. This seems neither dependent on the level of hypothermia nor on rewarming before fracture stabilization. Although rewarming before fracture stabilization has no significant effect on early survival, it does influence the proinflammatory response. The long-term effects (sepsis, MODS) of the hypothermia- and rewarming-induced changes of the pro- and anti-inflammatory response need to be examined in further experimental studies with a longer posttraumatic observation period.

If noted, the author indicates something of value received. The codes are identified as a-research or institutional support; b-miscellaneous funding; c-royalties; d-stock options; e-consultant or employee; n-no conflicts disclosed, and *disclosure not available at time of printing.