title: Induction of profound hypothermia modulates the immune/inflammatory response in a swine model of lethal hemorrhage.
abstract: Profound hypothermic arrest ("suspended animation") is a new strategy to improve outcome following uncontrolled lethal hemorrhage (ULH). However, the impact of this approach on the immune/inflammatory response is unknown. This experiment was conducted to test the influence of profound hypothermia on markers of immune/inflammatory system.
  
  
  METHODS
  ULH was induced in 32 female swine (80-120 lb) by creating an iliac artery and vein injury, followed 30 min later by laceration of the descending thoracic aorta. Through a left thoracotomy approach, total body hypothermic hyperkalemic metabolic arrest was induced by infusing organ preservation fluids into the aorta using a cardiopulmonary bypass machine (CPB). Experimental groups were (1) normothermic controls (no cooling, NC), or hypothermia induced at the following rates: (2) 0.5 degrees C/min (slow, SC), (3) 1 degrees C/min (medium, MC) and (4) 2 degrees C/min (fast, FC). Vascular injuries were repaired during 60 min of profound (10 degrees C) hypothermic arrest. Hyperkalemia was reversed by hypokalemic fluid exchange, and blood was infused for resuscitation during re-warming (0.5 degrees C/min). The surviving animals were monitored for 6 weeks. Levels of IL-1, TNFalpha, IL-6, IL-10, TGF-1 beta and heat shock protein (HSP-70) were measured by ELISA in serum samples collected serially during the experiment and post-operatively.
  
  
  RESULTS
  Some of the immune markers were influenced by the use of CPB, independent of hypothermia (decrease in TGF-1 beta and increase in IL-1 beta). Hypothermia caused a significant decrease in IL-6, and an increase in HSP-70 expression compared to normothermic controls, independent of the cooling rate. An increase in IL-10 levels was noted which was influenced by the rate of cooling (p<0.05, MC versus NC).
  
  
  CONCLUSIONS
  Profound hypothermia modulates the post-shock immune/inflammatory system by attenuating the pro-inflammatory IL-6, increasing anti-inflammatory IL-10 and augmenting the protective heat shock responses.
authors.affiliation: Trauma Research and Readiness Institute for Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Chen
authors.forename: Huazhen
authors.initials: H
authors.lastname: Chen
authors.forename: Peter
authors.initials: P
authors.lastname: Rhee
authors.forename: Elena
authors.initials: E
authors.lastname: Koustova
authors.forename: Eduardo C
authors.initials: EC
authors.lastname: Ayuste
authors.forename: Kaneatsu
authors.initials: K
authors.lastname: Honma
authors.forename: Amal
authors.initials: A
authors.lastname: Nadel
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007036:Hypothermia, Induced / Q000379:methods*; D018836:Inflammation Mediators / Q000032:analysis*; D011336:Probability; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D012771:Shock, Hemorrhagic / Q000276:immunology / Q000401:mortality* / Q000628:therapy*; D015996:Survival Rate; D013552:Swine
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators