Assessment of coagulopathy, endothelial injury, and inflammation after traumatic brain injury and hemorrhage in a porcine model

Martin Sillesen, Lars S. Rasmussen, Guang Jin, Cecilie H. Jepsen, Ayesha Imam, John O. Hwabejire, Ihab Halaweish, Marc DeMoya, George Velmahos, Pär I. Johansson, Hasan B. Alam

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

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, 30Y35 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. CONCLUSION: 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. (J Trauma Acute Care Surg. 2014;76: 12Y20.

Original languageEnglish (US)
Pages (from-to)12-20
Number of pages9
JournalJournal of Trauma and Acute Care Surgery
Volume76
Issue number1
DOIs
StatePublished - Jan 2014
Externally publishedYes

Keywords

  • Brain
  • Coagulopathy
  • Inflammation
  • Injury
  • Porcine
  • Shock

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Surgery

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