Single and repeated bleomycin intratracheal instillations lead to different biomechanical changes in lung tissue

Single dose of bleomycin induces acute alveolitis followed by a reparative process whilst a repeated dose results in progressive fibrosis, which may lead to distinct lung tissue biomechanical changes. To test this hypothesis, rats were intratracheally instilled with saline (N=11) or bleomycin (2.5U/kg) once (SD, N=8) or three times (RD, N=9) one week apart, and sacrificed 28 days after challenge. Forced oscillatory mechanics as well as the amount of collagen fibre and myeloperoxidase content (MPO(L)) were studied in lung tissue strips. Both elastic modulus (H), tissue damping (G), and MPO(L) increased only in RD-challenged rats. Although fibroblast focus was found in RD, collagen fibre content increased in both challenged groups. However, the amount of collagen fibre in SD group was not enough to induce lung tissue mechanical changes. In conclusion, repeated doses of bleomycin induce inflammatory and fibrogenic behaviour with biomechanical changes mimicking interstitial lung disease in humans.