title: Models of lower extremity damage in mice: time course of organ damage and immune response.
abstract: BACKGROUND
  Post-traumatic inflammatory changes have been identified as major causes of altered organ function and failure. Both hemorrhage and soft tissue damage induce these inflammatory changes. Exposure to heterologous bone in animal models has recently been shown to mimic this inflammatory response in a stable and reproducible fashion. This follow-up study tests the hypothesis that inflammatory responses are comparable between a novel trauma model ("pseudofracture", PFx) and a bilateral femur fracture (BFF) model.
  
  
  METHODS
  In C57BL/6 mice, markers for remote organ dysfunction and inflammatory responses were compared in four groups (control/sham/BFF/PFx) at the time points 2, 4, and 6 h.
  
  
  RESULTS
  Hepatocellular damage in BFF and PFx was highly comparable in extent and evolution, as shown by similar levels of NFkappaB activation and plasma ALT. Pulmonary inflammatory responses were also comparably elevated in both trauma models as early as 2 h after trauma as measured by myeloperoxidase activity (MPO). Muscle damage was provoked in both BFF and PFx mice over the time course, although BFF induced significantly higher AST and CK levels. IL-6 levels were also similar with early and sustained increases over time in both trauma models.
  
  
  CONCLUSIONS
  Both BFF and PFx create similar reproducible inflammatory and remote organ responses. PFx will be a useful model to study longer term inflammatory effects that cannot be studied using BFF.
authors.affiliation: Department of Orthopedic Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania 15261, USA.
authors.forename: Christoph L
authors.initials: CL
authors.lastname: Menzel
authors.forename: Roman
authors.initials: R
authors.lastname: Pfeifer
authors.forename: Sophie S
authors.initials: SS
authors.lastname: Darwiche
authors.forename: Philipp
authors.initials: P
authors.lastname: Kobbe
authors.forename: Roop
authors.initials: R
authors.lastname: Gill
authors.forename: Richard A
authors.initials: RA
authors.lastname: Shapiro
authors.forename: Patricia
authors.initials: P
authors.lastname: Loughran
authors.forename: Yoram
authors.initials: Y
authors.lastname: Vodovotz
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Scott
authors.forename: Mazen S
authors.initials: MS
authors.lastname: Zenati
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Billiar
authors.forename: Hans-Christoph
authors.initials: HC
authors.lastname: Pape
mesh_terms: D055371:Acute Lung Injury / Q000276:immunology / Q000473:pathology; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D003402:Creatine Kinase / Q000097:blood; D003444:Crush Syndrome / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D005264:Femoral Fractures / Q000276:immunology* / Q000473:pathology; D006470:Hemorrhage / Q000276:immunology / Q000473:pathology; D007108:Immune Tolerance / Q000502:physiology; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D015850:Interleukin-6 / Q000097:blood; D007869:Leg Injuries / Q000276:immunology* / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000276:immunology / Q000293:injuries / Q000473:pathology; D017695:Soft Tissue Injuries / Q000276:immunology* / Q000473:pathology
chemical_list: D015850:Interleukin-6; D001219:Aspartate Aminotransferases; D003402:Creatine Kinase