Induction of profound hypothermia modulates the immune/inflammatory response in a swine model of lethal hemorrhage

Zhang Chen, Huazhen Chen, Peter Rhee, Elena Koustova, Eduardo C. Ayuste, Kaneatsu Honma, Amal Nadel, Hasan B. Alam

Research output: Contribution to journalArticle

50 Scopus citations

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°C/min (slow, SC), (3) 1°C/min (medium, MC) and (4) 2°C/min (fast, FC). Vascular injuries were repaired during 60 min of profound (10°C) hypothermic arrest. Hyperkalemia was reversed by hypokalemic fluid exchange, and blood was infused for resuscitation during re-warming (0.5°C/min). The surviving animals were monitored for 6 weeks. Levels of IL-1, TNFα, IL-6, IL-10, TGF-1β 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-1β and increase in IL-1β). 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.

Original languageEnglish (US)
Pages (from-to)209-216
Number of pages8
JournalResuscitation
Volume66
Issue number2
DOIs
StatePublished - Aug 1 2005

Keywords

  • Bypass
  • Cytokine
  • Heat shock
  • Hypothermia
  • Shock
  • Thoracotomy
  • Trauma
  • Vascular injury

ASJC Scopus subject areas

  • Emergency Medicine
  • Emergency
  • Cardiology and Cardiovascular Medicine

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