title: Normal saline influences coagulation and endothelial function after traumatic brain injury and hemorrhagic shock in pigs.
abstract: BACKGROUND
  Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related deaths. These insults disrupt coagulation and endothelial systems. This study investigated whether previously reported differences in lesion size and brain swelling during normal saline (NS), colloids (Hextend [HEX]), and fresh frozen plasma (FFP) resuscitation are associated with differential effects on coagulation and endothelial systems.
  
  
  METHODS
  We subjected 15 Yorkshire swine to TBI and HS (40% blood volume), and kept in HS for 2 hours before resuscitation with NS, HEX, or FFP. Markers of endothelial activation (E-selectin, Intercellular adhesion molecule [ICAM]-1), coagulation activation (prothrombin fragment 1 + 2), and natural anticoagulation (activated protein C [aPC]) were determined in serum and brain whole cell lysates.
  
  
  RESULTS
  Serum levels of aPC were greater in the NS group (203 ± 30 pg/mL) compared with HEX (77 ± 28 pg/mL; P = .02) and FFP (110 ± 28 pg/mL; P = .09), as was PF 1 + 2 in the brain when compared with FFP (PF 1 + 2, 89 ± 46 vs 37 ± 14 ng/mL; P = .035). Brain E-selectin was greater in the NS group compared with FFP (3.36 ± 0.02 vs 3.31 ± 0.01 ng/mL; P = .029). Circulating ICAM-1 levels were increased in the NS group (151 ± 9 ng/mL) compared with the HEX (100 ± 9 ng/mL; P < .01) and FFP (108 ± 9 ng/mL; P = .01).
  
  
  CONCLUSIONS
  In this clinically realistic large animal model of TBI + HS, NS resuscitation was associated with an early activation of coagulation, natural anticoagulation, and endothelial systems, compared with HEX and FFP.
authors: Department of Surgery, University of Michigan Hospital, Ann Arbor, MI; Department of Anesthesiology, VU University Medical Center, Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors: Simone E
authors: SE
authors: Dekker
authors: Division of Trauma, Emergency Surgery and Surgical Critical Care, Department of Surgery, Massachusetts General Hospital/Harvard Medical School, Boston, MA; Department of Surgery, Copenhagen University Hospital, Hillerød, Denmark.
authors: Martin
authors: M
authors: Sillesen
authors: Department of Surgery, University of Michigan Hospital, Ann Arbor, MI.
authors: Ted
authors: T
authors: Bambakidis
authors: Department of Surgery, University of Michigan Hospital, Ann Arbor, MI.
authors: Guang
authors: G
authors: Jin
authors: Department of Surgery, University of Michigan Hospital, Ann Arbor, MI.
authors: Baoling
authors: B
authors: Liu
authors: Department of Anesthesiology, VU University Medical Center, Institute for Cardiovascular Research, Amsterdam, The Netherlands.
authors: Christa
authors: C
authors: Boer
authors: Capital Region Blood Bank, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark; Department of Surgery, Centre for Translational Injury Research (CeTIR), University of Texas Medical School, Houston, TX.
authors: Pär I
authors: PI
authors: Johansson
authors: Department of Surgery, University of Michigan Hospital, Ann Arbor, MI.
authors: Ihab
authors: I
authors: Halaweish
authors: Department of Surgery, University of Michigan Hospital, Ann Arbor, MI.
authors: Jake
authors: J
authors: Maxwell
authors: Department of Surgery, University of Michigan Hospital, Ann Arbor, MI. Electronic address: alamh@med.umich.edu.
authors: Hasan B
authors: HB
authors: Alam
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D001777:Blood Coagulation; D001921:Brain / Q000378:metabolism; D001930:Brain Injuries / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*; D003102:Colloids / Q000627:therapeutic use; D019040:E-Selectin / Q000097:blood / Q000378:metabolism; D004730:Endothelium, Vascular / Q000503:physiopathology*; D005260:Female; D005342:Fibrinolysis; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000378:metabolism; D007552:Isotonic Solutions / Q000627:therapeutic use; D010446:Peptide Fragments / Q000097:blood / Q000378:metabolism; D010949:Plasma; D011486:Protein C / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D012151:Resuscitation / Q000379:methods; D012771:Shock, Hemorrhagic / Q000097:blood / Q000503:physiopathology* / Q000628:therapy*; D012965:Sodium Chloride / Q000627:therapeutic use*; D034421:Sus scrofa
chemical_list: D015415:Biomarkers; D003102:Colloids; D019040:E-Selectin; D007552:Isotonic Solutions; D010446:Peptide Fragments; D011486:Protein C; C045879:prothrombin fragment 1.2; D018799:Intercellular Adhesion Molecule-1; D012965:Sodium Chloride; D011516:Prothrombin