Induced mild hypothermia reduces mortality during acute inflammation in rats.
BACKGROUND
Hypothermia has been proposed as a therapeutic possibility in brain trauma, cardiac arrest and hemorrhagic shock. Experimental studies have shown that hypothermia may act by modulating the inflammatory response during endotoxemia. This study was carried out to test whether hypothermia could protect rats from endotoxemic insult.


METHODS
After general anesthesia and oro-tracheal intubation, Sprague-Dawley rats were randomly assigned to either a hypothermic group or normothermic group. In each group, rats received intraperitoneal lipopolysaccharide (LPS) (10 or 20 mg/kg). Blood samples were taken prior to and 2 h after LPS injection to measure blood gases, liver enzymes, muscular enzymes, tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) plasma levels. After 2 h of hypothermia, the rats were extubated and brought back to their cages. The mortality rate was observed for 7 days following endotoxemia. In a second set of experiments, hypothermia was induced 1 h after endotoxemia (10 mg/kg of intraperitoneal LPS) and the mortality rate was observed for the following 7 days.


RESULTS
The survival rate was significantly increased in the hypothermic group relative to the normothermic group, regardless of LPS dose. This increased survival rate was also observed when hypothermia was induced 1 h after endotoxemia. In the hypothermic group, IL-10 and the DeltaIL-10/DeltaTNF-alpha ratio were significantly increased relative to those in the normothermic group.


CONCLUSIONS
Induced mild hypothermia reduces mortality during endotoxemia in rats. The modulation of the inflammatory response, with an increase in anti-inflammatory cytokines, may be involved in this protective effect.
Huet
O
O
Université Paris XI, Département d'Anesthésie Réanimation, Hôpital Bicêtre, Le Kremlin Bicêtre, France.
Kinirons
B
B
Dupic
L
L
Lajeunie
E
E
Mazoit
J X
JX
Benhamou
D
D
Vicaut
E
E
Duranteau
J
J
D000818:Animals; D001794:Blood Pressure; D019446:Endotoxemia / Q000401:mortality*; D006339:Heart Rate; D007036:Hypothermia, Induced; D018836:Inflammation Mediators / Q000378:metabolism; D016753:Interleukin-10 / Q000097:blood; D008070:Lipopolysaccharides; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015996:Survival Rate; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10