Extracellular matrix and oscillatory mechanics of rat lung parenchyma in bleomycin-induced fibrosis

We investigated in vivo and in vitro oscillatory mechanics in bleomycin-ind uced fibrotic lungs and correlated these with morphometric changes in the c ollagen-elastin matrix and contractile cells. Fischer rats received bleomyc in sulfate (BLEO,1.5 U) or saline intratracheally. Four weeks later trachea l flow and tracheal and alveolar pressure (using alveolar capsules) were me asured in open-chested rats during mechanical ventilation (VT = 8 ml/kg, f = 1 Hz, PEEP = 4 cm H2O). Total lung, tissue, and airway resistance (R) and lung elastance (E) were calculated. In addition, excised parenchymal strip s (70 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 effec ted 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 hys teresivity (17) were calculated. Strips were then exposed to acetylcholine (ACh, 10(-3) M). The amount of collagen and elastic fibers in the parenchym al strip was assessed semiquantitatively by point-counting in 5-mu m-thick sections stained with either Sirius Red or Weigert's Resorcin-fuchsin. alph a-Smoothmuscle-specific actin was detected immunohistochemically. Both in v ivo 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 rat s (p < 0.01). There was also a significant increase in the volume proportio n of collagen, elastic fibers, and actin in the parenchyma (p < 0.01). In B LEO rats, baseline R and E were correlated with the volume proportion of co llagen in the parenchyma. We conclude that changes in the collagen-elastin matrix contribute to changes in the viscoelastic properties of bleomycin-tr eated rat lungs.