title: Effect of protein C gene mutation on coagulation and inflammation in hemorrhagic shock.
abstract: BACKGROUND
  Trauma patients are at high risk of complications and death from coagulopathy and inflammatory organ failure. Recent evidence implicates protein C (PC) as a key mediator of this process. We hypothesized that a mutation in the PC gene would ameliorate the inflammatory and coagulopathic response to hemorrhagic shock (HS) and resuscitation.
  
  
  METHODS
  FHH wild type and PC mutant rats underwent controlled hemorrhage for 120 min with 70% of blood volume removed. Rats were resuscitated with Ringers lactate (2x shed blood volume) and shed blood. Animals were sacrificed 4 h post-HS. Controls were untreated naïve rats.
  
  
  RESULTS
  AST and NFkB lung protein levels were elevated similarly in both WT and mutants compared with naïve rats. Plasma fibrinogen levels decreased significantly with progression of HS compared with baseline (BL) levels and returned towards normal 4 h after resuscitation. PC activity was similar in both groups at BL (0.5 ± 0.08 versus 0.6 ± 0.14; P = 0.14) and decreased from BL by 53% ± 24% in WT (P =0.08), by 67% ± 11% in mutants (P = 0.03) at sacrifice, and was not different between groups (P = 0.29).
  
  
  CONCLUSIONS
  Our model of HS and resuscitation produced a hypocoaguable, hyperinflammatory state with increased levels of NFkB and decreased levels of fibrinogen and PC levels. The mutated PC did not appear to alter these responses in our model of HS and resuscitation.
authors.affiliation: Department of Surgery, University of California, Los Angeles, California, USA.
authors.forename: Sigrid
authors.initials: S
authors.lastname: Burruss
authors.forename: Arthur
authors.initials: A
authors.lastname: Andakyan
authors.forename: Sergei
authors.initials: S
authors.lastname: Romanov
authors.forename: Natalya
authors.initials: N
authors.lastname: Semiletova
authors.forename: Henry
authors.initials: H
authors.lastname: Cryer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001777:Blood Coagulation / Q000235:genetics*; D004195:Disease Models, Animal; D005440:Fluid Therapy; D007249:Inflammation / Q000235:genetics*; D007552:Isotonic Solutions / Q000627:therapeutic use; D009154:Mutation; D011486:Protein C / Q000235:genetics*; D051381:Rats; D012151:Resuscitation; D000077325:Ringer's Lactate; D012771:Shock, Hemorrhagic / Q000503:physiopathology* / Q000628:therapy
chemical_list: D015415:Biomarkers; D007552:Isotonic Solutions; D011486:Protein C; D000077325:Ringer's Lactate