Induced hypothermia reduces the hepatic inflammatory response in a swine multiple trauma model.
BACKGROUND
Mild therapeutic hypothermia following trauma has been introduced in several studies to reduce the posttraumatic inflammation and organ injury. In this study, we analyzed the effects of induced mild hypothermia (34°C) on the inflammation of the shock organs liver and kidney.


METHODS
In a porcine model of multiple trauma including blunt chest trauma, liver laceration, and hemorrhagic shock followed by fluid resuscitation, the influence of induced hypothermia on hepatic and renal damage and organ-specific inflammation were evaluated. A total of 40 pigs were randomly assigned to four groups, which were sham (anesthesia only) or trauma groups receiving either hypothermia or normothermia. The parameters analyzed were laboratory parameters (aspartate transaminase [AST], lactate dehydrogenase, urea, creatinine) as well as hepatic and renal cytokine expression determined by real-time polymerase chain reaction (interleukin 6 [IL-6], IL-8). Blinded analysis of histologic changes in the liver and kidney was performed.


RESULTS
Fifteen and a half hours following combined trauma, hepatic cytokine expression and liver damage were significantly increased in animals with normothermia compared with the respective sham group. Hypothermia, however, resulted in a fivefold reduced hepatic expression of IL-8 (mean ± SE, 2.4 ± 1.3; p = 0.01) when compared with the normothermic trauma group (IL-8, 12.8 ± 4.7). Accordingly, granulocyte infiltration and a histologic, semiquantitative score for liver injury were significantly higher in the normothermic trauma group. Serum AST levels raised significantly after trauma and normothermia compared with the respective sham group, while AST levels showed no difference from the sham groups in the hypothermic trauma group. In contrast, neither trauma nor hypothermia influenced the expression of IL-6 and IL-8 and tissue injury in the kidney.


CONCLUSIONS
Therapeutic hypothermia seems to attenuate the hepatic inflammatory response and the associated liver injury after severe trauma. Therefore, induced hypothermia might represent a potential therapeutic strategy to avoid posttraumatic organ dysfunction.
From the Department of Orthopaedic Trauma and Reconstructive Surgery (M.F., F.H., H.-C.P., R.P.), University Hospital Aachen, Aachen; Department of Orthopaedic Trauma Surgery (M.W.), University of Schleswig-Holstein, Kiel; Trauma Department (P.M.), Hannover Medical School, Hannover; Department of Trauma, Hand and Reconstructive Surgery (J.M., S.R.), University Hospital Marburg, Marburg; Department of Trauma and Hand-Surgery (I.W., S.F.), University of Duesseldorf, Duesseldorf; and Experimental Trauma Surgery (M.V.G.), Clinic for Trauma Surgery, Klinikum rechts der Isar, Technical University, Munich, Germany; and Ludwig Boltzmann Institute for Experimental and Clinical Traumatology (P.R., M.V.G.), Vienna, Austria.
Matthias
M
Fröhlich
Frank
F
Hildebrand
Matthias
M
Weuster
Philipp
P
Mommsen
Juliane
J
Mohr
Ingo
I
Witte
Pierre
P
Raeven
Steffen
S
Ruchholtz
Sascha
S
Flohé
Martijn
M
van Griensven
Hans-Christoph
HC
Pape
Roman
R
Pfeifer
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004247:DNA / Q000235:genetics; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D006098:Granulocytes / Q000473:pathology; D007036:Hypothermia, Induced / Q000379:methods*; D007249:Inflammation / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009104:Multiple Trauma / Q000150:complications / Q000378:metabolism / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction; D013552:Swine
D016207:Cytokines; D004247:DNA