title: Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model.
abstract: BACKGROUND
  Traumatic brain injury (TBI) and hemorrhagic shock (HS) can be associated with coagulopathy and inflammation, but the mechanisms are poorly understood. We hypothesized that a combination of TBI and HS would disturb coagulation, damage the endothelium, and activate inflammatory and complement systems.
  
  
  METHODS
  A total of 33 swine were allocated to either TBI + HS (n = 27, TBI and volume-controlled 40% blood loss) or controls (n = 6, anesthesia and instrumentation). TBI + HS animals were left hypotensive (mean arterial pressure, 30-35 mm Hg) for 2 hours. Blood samples were drawn at baseline, 3 minutes and 15 minutes after injury, as well as following 2 hours of hypotension. Markers of coagulation, anticoagulation, endothelial activation/glycocalyx shedding, inflammation, complement, and sympathoadrenal function were measured.
  
  
  RESULTS
  The TBI + HS group demonstrated an immediate (3 minutes after injury) activation of coagulation (prothrombin fragment 1 + 2, 289 ng/mL vs. 232 ng/mL, p = 0.03) and complement (C5a, 2.83 ng/mL vs. 2.05 ng/mL, p = 0.05). Shedding of the endothelial glycocalyx (syndecan 1) was evident 15 minutes after injury (851.0 ng/ml vs. 715.5 ng/ml, p = 0.03) while inflammation (tumor necrosis factor α [TNF-α], 81.1 pg/mL vs. 50.8 pg/mL, p = 0.03) and activation of the protein C system (activated protein C, 56.7 ng/mL vs. 26.1 ng/mL, p = 0.01) were evident following the 2-hour hypotension phase.
  
  
  CONCLUSIONS
  The combination of TBI and shock results in an immediate activation of coagulation and complement systems with subsequent endothelial shedding, protein C activation, and inflammation.
authors.affiliation: From the Division of Trauma, Emergency Surgery and Surgical Critical Care (M.S., C.H.J., A.I., J.O.H., M.D., G.V.), Department of Surgery, Massachusetts GeneralHospital/Harvard Medical School, Boston, Massachusetts; Department of Surgery (G.J., I.H., H.B.A.), University of Michigan, Ann Arbor, Michigan; and Department of Surgery (P.I.J.), University of Texas Medical School, Houston, Texas; and Department of Anesthesia (M.S., L.S.R.), Center of Head and Orthopedics, and Capital Region Blood Bank (C.H.J., P.I.J.), Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Sillesen
authors.forename: Lars S
authors.initials: LS
authors.lastname: Rasmussen
authors.forename: Guang
authors.initials: G
authors.lastname: Jin
authors.forename: Cecilie H
authors.initials: CH
authors.lastname: Jepsen
authors.forename: Ayesha
authors.initials: A
authors.lastname: Imam
authors.forename: John O
authors.initials: JO
authors.lastname: Hwabejire
authors.forename: Ihab
authors.initials: I
authors.lastname: Halaweish
authors.forename: Marc
authors.initials: M
authors.lastname: DeMoya
authors.forename: George
authors.initials: G
authors.lastname: Velmahos
authors.forename: Pär I
authors.initials: PI
authors.lastname: Johansson
authors.forename: Hasan B
authors.initials: HB
authors.lastname: Alam
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000031:analogs & derivatives; D001778:Blood Coagulation Disorders / Q000209:etiology*; D001930:Brain Injuries / Q000150:complications*; D003167:Complement Activation; D004195:Disease Models, Animal; D004727:Endothelium / Q000293:injuries; D005260:Female; D005342:Fibrinolysis; D006470:Hemorrhage / Q000150:complications* / Q000209:etiology; D007249:Inflammation / Q000209:etiology*; D012771:Shock, Hemorrhagic / Q000150:complications / Q000209:etiology; D013552:Swine
chemical_list: C087337:6-S-hexadecyl-2-methoxythioascorbic acid; D001205:Ascorbic Acid