title: Fibrinolysis shutdown phenotype masks changes in rodent coagulation in tissue injury versus hemorrhagic shock.
abstract: BACKGROUND
  Systemic hyperfibrinolysis (accelerated clot degradation) and fibrinolysis shutdown (impaired clot degradation) are associated with increased mortality compared with physiologic fibrinolysis after trauma. Animal models have not reproduced these changes. We hypothesize rodents have a shutdown phenotype that require an exogenous profibrinolytic to differentiate mechanisms that promote or inhibit fibrinolysis.
  
  
  METHODS
  Fibrinolysis resistance was assessed by thrombelastography (TEG) using exogenous tissue plasminogen activator (tPA) titrations in whole blood. There were 3 experimental groups: (1) tissue injury (laparotomy/bowel crush), (2) shock (hemorrhage to mean arterial pressure of 20 mmHg), and (3) control (arterial cannulation and tracheostomy). Baseline and 30-minute postintervention blood samples were collected, and assayed with TEG challenged with taurocholic acid (TUCA).
  
  
  RESULTS
  Rats were resistant to exogenous tPA; the percent clot remaining 30 minutes after maximum amplitude (CL30) at 150 ng/mL (P = .511) and 300 ng/mL (P = .931) was similar to baseline, whereas 600 ng/mL (P = .046) provoked fibrinolysis. Using the TUCA challenge, the percent change in CL30 from baseline was increased in tissue injury compared with control (P = .048.), whereas CL30 decreased in shock versus control (P = .048). tPA increased in the shock group compared with tissue injury (P = .009) and control (P = .012).
  
  
  CONCLUSIONS
  Rats have an innate fibrinolysis shutdown phenotype. The TEG TUCA challenge is capable of differentiating changes in clot stability with rats undergoing different procedures. Tissue injury inhibits fibrinolysis, whereas shock promotes tPA-mediated fibrinolysis.
authors.affiliation: Denver Health Medical Center, Department of Surgery, Denver, CO; University of Colorado Denver, Department of Surgery, Denver, CO. Electronic address: hunter.moore@ucdenver.edu.
authors.forename: Hunter B
authors.initials: HB
authors.lastname: Moore
authors.affiliation: Denver Health Medical Center, Department of Surgery, Denver, CO; University of Colorado Denver, Department of Surgery, Denver, CO.
authors.forename: Ernest E
authors.initials: EE
authors.lastname: Moore
authors.affiliation: Denver Health Medical Center, Department of Surgery, Denver, CO.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Lawson
authors.affiliation: Denver Health Medical Center, Department of Surgery, Denver, CO; University of Colorado Denver, Department of Surgery, Denver, CO.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Gonzalez
authors.affiliation: Denver Health Medical Center, Department of Surgery, Denver, CO.
authors.forename: Miguel
authors.initials: M
authors.lastname: Fragoso
authors.affiliation: Denver Health Medical Center, Department of Surgery, Denver, CO; University of Colorado Denver, Department of Surgery, Denver, CO.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Morton
authors.affiliation: University of Colorado Denver, Department of Surgery, Denver, CO.
authors.forename: Fabia
authors.initials: F
authors.lastname: Gamboni
authors.affiliation: Denver Health Medical Center, Department of Surgery, Denver, CO.
authors.forename: Michael P
authors.initials: MP
authors.lastname: Chapman
authors.affiliation: University of Colorado Denver, Department of Surgery, Denver, CO.
authors.forename: Angela
authors.initials: A
authors.lastname: Sauaia
authors.affiliation: University of Colorado Denver, Department of Surgery, Denver, CO.
authors.forename: Anirban
authors.initials: A
authors.lastname: Banerjee
authors.affiliation: University of Colorado Denver, Department of Surgery, Denver, CO; University of Colorado Denver, Department of Pediatrics, Denver, CO; Bonfils Blood Center, Denver, CO.
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Silliman
mesh_terms: D000007:Abdominal Injuries / Q000097:blood*; D000818:Animals; D004195:Disease Models, Animal; D005342:Fibrinolysis / Q000187:drug effects* / Q000502:physiology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D008297:Male; D010641:Phenotype; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012771:Shock, Hemorrhagic / Q000097:blood*; D013656:Taurocholic Acid / Q000494:pharmacology; D013916:Thrombelastography; D010959:Tissue Plasminogen Activator / Q000494:pharmacology*
chemical_list: D005343:Fibrinolytic Agents; D013656:Taurocholic Acid; D010959:Tissue Plasminogen Activator