title: Long-Term Effects of Induced Hypothermia on Local and Systemic Inflammation - Results from a Porcine Long-Term Trauma Model.
abstract: Hypothermia has been discussed as playing a role in improving the early phase of systemic inflammation. However, information on the impact of hypothermia on the local inflammatory response is sparse. We therefore investigated the kinetics of local and systemic inflammation in the late posttraumatic phase after induction of hypothermia in an established porcine long-term model of combined trauma.
  
  
  
  Male pigs (35 ± 5kg) were mechanically ventilated and monitored over the study period of 48 h. Combined trauma included tibia fracture, lung contusion, liver laceration and pressure-controlled hemorrhagic shock (MAP < 30 ± 5 mmHg for 90 min). After resuscitation, hypothermia (33°C) was induced for a period of 12 h (HT-T group) with subsequent re-warming over a period of 10 h. The NT-T group was kept normothermic. Systemic and local (fracture hematoma) cytokine levels (IL-6, -8, -10) and alarmins (HMGB1, HSP70) were measured via ELISA.
  
  
  
  Severe signs of shock as well as systemic and local increases of pro-inflammatory mediators were observed in both trauma groups. In general the local increase of pro- and anti-inflammatory mediator levels was significantly higher and prolonged compared to systemic concentrations. Induction of hypothermia resulted in a significantly prolonged elevation of both systemic and local HMGB1 levels at 48 h compared to the NT-T group. Correspondingly, local IL-6 levels demonstrated a significantly prolonged increase in the HT-T group at 48 h.
  
  
  
  A prolonged inflammatory response might reduce the well-described protective effects on organ and immune function observed in the early phase after hypothermia induction. Furthermore, local immune response also seems to be affected. Future studies should aim to investigate the use of therapeutic hypothermia at different degrees and duration of application.
authors.affiliation: Department of Orthopedic Trauma and Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Horst
authors.affiliation: Department of Hand, Traumatology and Reconstructive Surgery, University Hospital Marburg, Marburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Eschbach
authors.affiliation: Department of Orthopedic Trauma and Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Pfeifer
authors.affiliation: Department of Trauma, Hand and Reconstructive Surgery, Goethe University Frankfurt am Main, Frankfurt, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Relja
authors.affiliation: Department of Anesthesiology, University Hospital Marburg, Marburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sassen
authors.affiliation: Department of Anesthesiology, University Hospital Marburg, Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Steinfeldt
authors.affiliation: Department of Anesthesiology, University Hospital Marburg, Marburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wulf
authors.affiliation: Department of Neurosurgery, University Hospital Giessen, Giessen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Vogt
authors.affiliation: Department of Hand, Traumatology and Reconstructive Surgery, University Hospital Marburg, Marburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Frink
authors.affiliation: Department of Hand, Traumatology and Reconstructive Surgery, University Hospital Marburg, Marburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Ruchholtz
authors.affiliation: Department of Orthopedic Trauma and Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: H C
authors.initials: HC
authors.lastname: Pape
authors.affiliation: Department of Orthopedic Trauma and Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstraße 30, 52074 Aachen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hildebrand
mesh_terms: D000818:Animals; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D006406:Hematoma / Q000378:metabolism / Q000473:pathology; D007036:Hypothermia, Induced / Q000379:methods*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology*; D022125:Lacerations / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D055370:Lung Injury / Q000378:metabolism / Q000473:pathology; D008297:Male; D009104:Multiple Trauma / Q000378:metabolism / Q000473:pathology*; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000378:metabolism / Q000473:pathology; D034421:Sus scrofa; D013552:Swine
chemical_list: D016207:Cytokines