Extracellular Matrix and Oscillatory Mechanics of Rat Lung Parenchyma in Bleomycin-induced Fibrosis

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Abstract
We investigated in vivo and in vitro oscillatory mechanics in bleomycin-induced fibrotic lungs and correlated these with morphometric changes in the collagen-elastin matrix and contractile cells. Fischer rats received bleomycin sulfate (BLEO,1.5 U) or saline intratracheally. Four weeks later tracheal flow and tracheal and alveolar pressure (using alveolar capsules) were measured in open-chested rats during mechanical ventilation (V T = 8 ml/kg, f = 1 Hz, PEEP = 4 cm H(2)O). Total lung, tissue, and airway resistance (R) and lung elastance (E) were calculated. In addition, excised parenchymal strips (10 x 2 x 2 mm) were studied in the organ bath. Strips were attached to a force transducer at one end and to a servo-controlled lever arm that effected length (L) changes at the other. Sinusoidal oscillations were applied (f = 1 Hz, amplitude = 2. 5% resting L and tension = 0.7 g) and R, E, and hysteresivity (eta) were calculated. Strips were then exposed to acetylcholine (ACh, 10(-)(3) M). The amount of collagen and elastic fibers in the parenchymal strip was assessed semiquantitatively by point-counting in 5-micrometer-thick sections stained with either Sirius Red or Weigert's Resorcin-fuchsin. alpha-Smooth-muscle-specific actin was detected immunohistochemically. Both in vivo and in vitro, R, E, and eta were significantly increased in BLEO rats (p < 0.05). The % increase in R, E and eta after Ach was greater in BLEO rats (p < 0. 01). There was also a significant increase in the volume proportion of collagen, elastic fibers, and actin in the parenchyma (p < 0.01). In BLEO rats, baseline R and E were correlated with the volume proportion of collagen in the parenchyma. We conclude that changes in the collagen-elastin matrix contribute to changes in the viscoelastic properties of bleomycin-treated rat lungs. Dolhnikoff M, Mauad T, Ludwig MS. Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin-induced fibrosis.

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