Hypothermia prolongs the survival of rats with severe septic shock by inhibiting the splenic release of neutrophils and monocytes

Rhett N. Willis, University of Virginia Health System; Christopher Guidry, UVA Health System; Robert Sawyer, University of Virginia HSC; Zequan Yang, University of Virginia HSC

Severe sepsis following bacteremia can result in diffuse end organ damage and increased mortality. The spleen is an important defense organ to fight against bacteremia but could worsen the septic shock by exaggerating inflammatory responses.

We hypothesize that hypothermia therapy will increase overall survival in rats with severe septic shock by inhibiting the splenic release of inflammatory neutrophils and monocytes

This study involves inducing a severe septic rat model by cecal ligation and incision (CLI). Hypothermia was induced using cooling blanket to cool the rectal temperature to 31°C. One hour after CLI, rats were assigned to normothermic or hypothermic groups for 4 hours with 2 additional hours of rewarming for the hypothermic group. Survival was the endpoint. In an additional two groups, the spleen was harvested at one hour after hypo- or normothermic treatment.

Survival duration was 2.70±0.79hr in normothermic rats (N=8) and 8.30±0.42hr in hypothermic rats (N=8), (p<0.0001) by Kaplan Myer Curve. The spleen weight was significantly lower in normothermic rats (0.72±0.07gm) than in hypothermic rats (0.81±0.10gm) (p<0.05) by Kaplan Myer Curve as expressed in Figure 1. Immunostaining for the expression of formyl peptide receptors (FPR), indicating the presence of neutrophils/monocytes in the spleen, was considerably higher in hypothermic rats than in the normothermic rats, as shown in Figure 2.

Hypothermia therapy significantly prolongs the survival of rats with severe septic shock. Hypothermia dampens the inflammatory response during septic shock by preventing the spleen from releasing activated monocytes/neutrophils into the blood.