Effects of hypothermia and re-warming on the inflammatory response in a murine multiple hit model of trauma.
BACKGROUND
Although, hypothermia is a frequent event after trauma, it is unclear whether its beneficial or detrimental effects are more important. This study aims to quantify the effects of hypothermia and re-warming on the inflammatory response after fracture/hemorrhage and subsequent fracture stabilization with resuscitation.


METHODS
Eighty-one male C57Bl/6 mice (aged 8-10 weeks, weighing 22.0+/-3.0 g) underwent femoral fracture and hemorrhage followed by resuscitation and splint fixation of the fracture. Animals were sacrificed 3h after induction of hemorrhage and fracture. Besides a sham group (n=6), four experimental groups were created: A: normothermia (n=12), B: hypothermia after trauma (n=21), C: re-warming after resuscitation and before stabilization (n=21), and D: hypothermia before trauma (n=21). Groups B-D were further subdivided into three subgroups according to the degree of hypothermia (subgroup 1: 35-33 degrees C, subgroup 2: 32.9-30.0 degrees C, and subgroup 3: 29.9-27.0 degrees C). Plasma cytokine (TNF-alpha, IL-6, and IL-10) and chemokine (MCP-1) concentrations were determined by ELISA, pulmonary permeability changes were quantified, and histological analysis of lung and liver tissues was performed.


RESULTS
Normothermia resulted in a significantly increased early mortality rate. A significantly increased pro-inflammatory and decreased anti-inflammatory responses were also observed in normothermia as compared to hypothermia. The extent of these changes was most pronounced in the severe hypothermic group. Re-warming after mild hypothermia resulted in a pro-inflammatory response comparable to normothermia.


CONCLUSIONS
Hypothermia has a beneficial effect on early survival after trauma, which appears to be independent of the level of hypothermia and re-warming. Re-warming, however, enhanced the pro-inflammatory response. Further studies with a longer posttraumatic observation period are required to investigate the long term effects of the hypothermia and re-warming-induced changes on the pro- and anti-inflammatory responses.
Hildebrand
Frank
F
Trauma Department, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. hildebrand.frank@mh-hannover.de
van Griensven
Martijn
M
Giannoudis
Peter
P
Luerig
Astrid
A
Harwood
Paul
P
Harms
Oliver
O
Fehr
Michael
M
Krettek
Christian
C
Pape
Hans-Christoph
HC
D000818:Animals; D001831:Body Temperature; D018893:Bronchoalveolar Lavage; D018932:Chemokine CCL2 / Q000097:blood; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005269:Femur / Q000473:pathology; D017102:Fracture Healing; D006470:Hemorrhage; D007036:Hypothermia, Induced; D007249:Inflammation / Q000628:therapy*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017694:Rewarming; D013696:Temperature; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014947:Wounds and Injuries / Q000628:therapy*
D018932:Chemokine CCL2; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10