title: Impact of haemorrhagic shock intensity on the dynamic of alarmins release in porcine poly-trauma animal model.
abstract: OBJECTIVE
  Traumatic insults result in an altered inflammatory response, in which alarmins release has a central role. The impact of haemorrhagic shock intensity on the long-term kinetics of alarmins is not yet fully elucidated. We investigated these aspects in a combined trauma (chest, abdominal, and extremities injury) porcine model with different severities and durations of haemorrhagic shock.
  
  
  METHODS
  After induction of combined trauma (tibia fracture, lung contusion, and liver laceration), haemorrhagic shock was induced at different intensities: moderate haemorrhage (MH; n = 15): mean arterial pressure (MAP) <30 ± 5 mmHg [maximum loss of total blood volume (TBVmax): 45 %] for 90 min, and severe haemorrhage (SH; n = 10): MAP <25 ± 5 mmHg (TBVmax 50 %) for 120 min. Resuscitation was performed using a standardized crystalloid infusion protocol. Animals were mechanically ventilated and underwent ICU-monitoring for 48 h (MH) and 48.5 h (SH). Blood samples were collected over the clinical time course, and systemic levels of serum alarmins [High-Mobility Group Protein B-1 (HMGB-1) and Heat Shock Protein 70 (HSP70)] were measured using an ELISA kit.
  
  
  RESULTS
  Heart rate, systemic blood pressure, lactate, and base excess were significantly altered as a function of haemorrhagic shock in both trauma groups (MH and SH). Systemic HMGB-1 levels were significantly elevated in both trauma groups when compared to the sham group. Haemorrhagic shock severity and duration were positively correlated with HMGB-1 levels and compared to baseline values, concentrations remained significantly increased in SH when compared to MH. On the other hand, we observed a significant decrease in the systemic HSP70 levels of trauma groups (MH, and SH) when compared to the sham group, which was significantly decreased compared to baseline values in SH over the entire time course.
  
  
  CONCLUSIONS
  Our data show that haemorrhagic shock duration and severity affect the systemic levels of HMGB-1 and HSP70. This early alarmins release after trauma can be used to guide the treatment strategies (e.g. surgical procedures) of polytrauma patients.
authors.affiliation: Department of Orthopaedic Trauma, Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany. khorst@ukaachen.de.
authors.forename: K
authors.initials: K
authors.lastname: Horst
authors.affiliation: Department of Orthopaedic Trauma, Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Hildebrand
authors.affiliation: Department of Orthopaedic Trauma, 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 Orthopaedic Trauma, Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Hübenthal
authors.affiliation: Department of Orthopaedic Trauma, Harald Tscherne Research Laboratory, University Hospital Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Almahmoud
authors.affiliation: Department of Anaesthesiology, University Hospital Marburg, Marburg, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sassen
authors.affiliation: Department of Anaesthesiology, University Hospital Marburg, Marburg, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Steinfeldt
authors.affiliation: Department of Anaesthesiology, University Hospital Marburg, Marburg, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Wulf
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 Orthopaedic Trauma, 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 Hand, Traumatology and Reconstructive Surgery, University Hospital Marburg, Marburg, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Eschbach
mesh_terms: D000067531:Alarmins / Q000378:metabolism; D000818:Animals; D003288:Contusions; D000077324:Crystalloid Solutions; D004195:Disease Models, Animal; D005440:Fluid Therapy; D024243:HMGB1 Protein / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D007552:Isotonic Solutions; D022125:Lacerations; D008099:Liver / Q000293:injuries; D055370:Lung Injury; D008297:Male; D009104:Multiple Trauma / Q000150:complications / Q000378:metabolism*; D012121:Respiration, Artificial; D012151:Resuscitation; D012720:Severity of Illness Index; D012771:Shock, Hemorrhagic / Q000209:etiology / Q000378:metabolism*; D034421:Sus scrofa; D013552:Swine; D013978:Tibial Fractures
chemical_list: D000067531:Alarmins; D000077324:Crystalloid Solutions; D024243:HMGB1 Protein; D018840:HSP70 Heat-Shock Proteins; D007552:Isotonic Solutions
keywords: HMGB-1; HSP70; Haemorrhagic shock intensity; Multiple trauma; Polytrauma; Porcine model