title: Myocardial gene expression profiling of rewarming shock in a rodent model of accidental hypothermia.
abstract: BACKGROUND
  Severe accidental hypothermia represents a cardiovascular emergency associated with high mortality and poor recovery of cardiac function. The biochemical changes occurring within the heart during the development of hypothermia and subsequent resuscitation are not known.
  
  
  METHODS
  By mRNA expression profiling, we have characterized gene expression changes occurring within the myocardium in an intact rat model of accidental hypothermia during cooling to a core temperature of 15 °C and subsequent rewarming to 37 °C. During the rewarming phase, these animals develop a profound low-output cardiac failure.
  
  
  RESULTS
  Hypothermia induces expression of known mediators of thermotolerance, including heat-shock protein 70 and several factors involved in protection against apoptotic cell death. Upregulation of genes involved in autophagy and increased abundance of autophagosomal vesicles suggest involvement of autophagic degeneration in the development of myocardial dysfunction occurring during rewarming from hypothermia. Rewarming from hypothermia also induces expression of several pro-inflammatory genes involved in the nuclear factor kappa B (NFκB) signaling cascade.
  
  
  CONCLUSIONS
  Our data demonstrate that rewarming from hypothermia is associated with the induction of a cellular stress-response, including upregulation of autophagy and activation of pro-inflammatory signaling cascades. These data provide a framework for understanding the molecular changes that occur during induction of and rewarming from severe hypothermia, and identifies potential targets for cardioprotective interventions in resuscitation of victims of hypothermia.
authors.affiliation: Department of Biochemistry, Institute of Medical Biology, University of Tromsø, N-9037 Tromsø, Norway. Anders.Aune.Tveita@uit.no
authors.forename: Anders Aune
authors.initials: AA
authors.lastname: Tveita
authors.forename: Erik Sveberg
authors.initials: ES
authors.lastname: Dietrichs
authors.forename: Torkjel
authors.initials: T
authors.lastname: Tveita
mesh_terms: D000818:Animals; D001343:Autophagy / Q000235:genetics; D001831:Body Temperature; D002302:Cardiac Output; D003080:Cold Temperature; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006333:Heart Failure / Q000209:etiology / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007035:Hypothermia / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D046228:Microarray Analysis; D023421:Models, Animal; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012151:Resuscitation; D017694:Rewarming / Q000009:adverse effects*; D012377:Rodentia; D015398:Signal Transduction
chemical_list: D018840:HSP70 Heat-Shock Proteins; D016328:NF-kappa B