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Open Access Research article

Static and dynamic mechanics of the murine lung after intratracheal bleomycin

Effrosyni D Manali1, Charalampos Moschos1, Christina Triantafillidou1, Anastasia Kotanidou23, Ioannis Psallidas1, Sophia P Karabela2, Charis Roussos23, Spyridon Papiris1, Apostolos Armaganidis4, Georgios T Stathopoulos2 and Nikolaos A Maniatis4*

Author Affiliations

1 2nd Pulmonary Department, "Attikon" General Hospital, National and Kapodistrian University of Athens Medical School, Haidari, Greece

2 Applied Biomedical Research & Training Center "Marianthi Simou", 1st Dept. of Critical Care & Pulmonary Services, "Evangelismos" General Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece

3 1st Dept. of Critical Care & Pulmonary Services, "Evangelismos" General Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece

4 2nd Dept. of Critical Care, "Attikon" General Hospital, National and Kapodistrian University of Athens Medical School, Haidari, Greece

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BMC Pulmonary Medicine 2011, 11:33  doi:10.1186/1471-2466-11-33

Published: 31 May 2011

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.