title: Effects of pretreatment hypothermia during resuscitated porcine hemorrhagic shock.
abstract: OBJECTIVE
  Accidental hypothermia increases mortality and morbidity after hemorrhage, but controversial data are available on the effects of therapeutic hypothermia. Therefore, we tested the hypothesis whether moderate pretreatment hypothermia would beneficially influence organ dysfunction during long-term, porcine hemorrhage and resuscitation.
  
  
  METHODS
  Prospective, controlled, randomized study.
  
  
  METHODS
  University animal research laboratory.
  
  
  METHODS
  Twenty domestic pigs of either gender.
  
  
  METHODS
  Using an extracorporeal heat exchanger, anesthetized and instrumented animals were maintained at 38°C, 35°C, or 32°C core temperature and underwent 4 hours of hemorrhage (removal of 40% of the blood volume and subsequent blood removal/retransfusion to maintain mean arterial pressure at 30 mm Hg). Resuscitation comprised of hydroxyethyl starch and norepinephrine infusion titrated to maintain mean arterial pressure at preshock values.
  
  
  RESULTS
  Before, immediately at the end of, and 12 and 22 hours after hemorrhage, we measured systemic and regional hemodynamics (portal vein, hepatic and right kidney artery ultrasound flow probes) and oxygen transport, and nitric oxide and cytokine production. Hemostasis was assessed by rotation thromboelastometry. Postmortem biopsies were analyzed for histomorphology (hematoxylin and eosin staining) and markers of apoptosis (kidney Bcl-xL and caspase-3 expression). Hypothermia at 32°C attenuated the shock-related lactic acidosis but caused metabolic acidosis, most likely resulting from reduced carbohydrate oxidation. Although hypothermia did not further aggravate shock-related coagulopathy, it caused a transitory attenuation of kidney and liver dysfunction, which was ultimately associated with reduced histological damage and more pronounced apoptosis.
  
  
  CONCLUSIONS
  During long-term porcine hemorrhage and resuscitation, moderate pretreatment hypothermia was associated with a transitory attenuation of organ dysfunction and less severe histological tissue damage despite more pronounced metabolic acidosis. This effect is possibly due to a switch from necrotic to apoptotic cell death, ultimately resulting from reduced tissue energy deprivation during the shock phase.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Klinik für Anästhesiologie, Ulm, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Gröger
authors.forename: Angelika
authors.initials: A
authors.lastname: Scheuerle
authors.forename: Florian
authors.initials: F
authors.lastname: Wagner
authors.forename: Florian
authors.initials: F
authors.lastname: Simon
authors.forename: José
authors.initials: J
authors.lastname: Matallo
authors.forename: Oscar
authors.initials: O
authors.lastname: McCook
authors.forename: Andrea
authors.initials: A
authors.lastname: Seifritz
authors.forename: Bettina
authors.initials: B
authors.lastname: Stahl
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wachter
authors.forename: Josef A
authors.initials: JA
authors.lastname: Vogt
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Martin
authors.initials: M
authors.lastname: Matejovic
authors.forename: Peter
authors.initials: P
authors.lastname: Möller
authors.forename: Lorenz
authors.initials: L
authors.lastname: Lampl
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bracht
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
authors.forename: Michael
authors.initials: M
authors.lastname: Georgieff
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Stahl
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis; D005260:Female; D005947:Glucose / Q000378:metabolism; D006439:Hemodynamics; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods*; D012771:Shock, Hemorrhagic / Q000097:blood / Q000628:therapy*; D013552:Swine; D013997:Time Factors
chemical_list: D005947:Glucose