title: Static and dynamic mechanics of the murine lung after intratracheal bleomycin.
abstract: BACKGROUND
  Despite its widespread use in pulmonary fibrosis research, the bleomycin mouse model has not been thoroughly validated from a pulmonary functional standpoint using new technologies. Purpose of this study was to systematically assess the functional alterations induced in murine lungs by fibrogenic agent bleomycin and to compare the forced oscillation technique with quasi-static pressure-volume curves in mice following bleomycin exposure.
  
  
  METHODS
  Single intratracheal injections of saline (50 μL) or bleomycin (2 mg/Kg in 50 μL saline) were administered to C57BL/6 (n=40) and Balb/c (n=32) mice. Injury/fibrosis score, tissue volume density (TVD), collagen content, airway resistance (RN), tissue damping (G) and elastance coefficient (H), hysteresivity (η), and area of pressure-volume curve (PV-A) were determined after 7 and 21 days (inflammation and fibrosis stage, respectively). Statistical hypothesis testing was performed using one-way ANOVA with LSD post hoc tests.
  
  
  RESULTS
  Both C57BL/6 and Balb/c mice developed weight loss and lung inflammation after bleomycin. However, only C57BL/6 mice displayed cachexia and fibrosis, evidenced by increased fibrosis score, TVD, and collagen. At day 7, PV-A increased significantly and G and H non-significantly in bleomycin-exposed C57BL/6 mice compared to saline controls and further increase in all parameters was documented at day 21. G and H, but not PV-A, correlated well with the presence of fibrosis based on histology, TVD and collagen. In Balb/c mice, no change in collagen content, histology score, TVD, H and G was noted following bleomycin exposure, yet PV-A increased significantly compared to saline controls.
  
  
  CONCLUSIONS
  Lung dysfunction in the bleomycin model is more pronounced during the fibrosis stage rather than the inflammation stage. Forced oscillation mechanics are accurate indicators of experimental bleomycin-induced lung fibrosis. Quasi-static PV-curves may be more sensitive than forced oscillations at detecting inflammation and fibrosis.
authors.affiliation: 2nd Pulmonary Department, Attikon General Hospital, National and Kapodistrian University of Athens Medical School, Haidari, Greece.
authors.forename: Effrosyni D
authors.initials: ED
authors.lastname: Manali
authors.forename: Charalampos
authors.initials: C
authors.lastname: Moschos
authors.forename: Christina
authors.initials: C
authors.lastname: Triantafillidou
authors.forename: Anastasia
authors.initials: A
authors.lastname: Kotanidou
authors.forename: Ioannis
authors.initials: I
authors.lastname: Psallidas
authors.forename: Sophia P
authors.initials: SP
authors.lastname: Karabela
authors.forename: Charis
authors.initials: C
authors.lastname: Roussos
authors.forename: Spyridon
authors.initials: S
authors.lastname: Papiris
authors.forename: Apostolos
authors.initials: A
authors.lastname: Armaganidis
authors.forename: Georgios T
authors.initials: GT
authors.lastname: Stathopoulos
authors.forename: Nikolaos A
authors.initials: NA
authors.lastname: Maniatis
mesh_terms: D000403:Airway Resistance / Q000502:physiology; D000818:Animals; D001761:Bleomycin / Q000008:administration & dosage / Q000009:adverse effects*; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D004548:Elasticity / Q000502:physiology; D007267:Injections; D008168:Lung / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011658:Pulmonary Fibrosis / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D015656:Respiratory Mechanics / Q000502:physiology*; D012720:Severity of Illness Index; D014132:Trachea
chemical_list: D001761:Bleomycin; D003094:Collagen