Overexpression of TGF-alpha increases lung tissue hysteresivity in transgenic mice

Increased transforming growth factor (TGF)-alpha has been observed in neona tal chronic lung disease. Lungs of transgenic mice that overexpress TGF-alp ha develop enlarged air spaces and pulmonary fibrosis compared with wild-ty pe mice. We hypothesized that these pathological changes may alter the mech anical coupling of viscous and elastic forces within lung parenchyma. Respi ratory impedance was measured in open-chested, tracheostomized adult wild-t ype and TGF-alpha mice by using the forced oscillation technique (0.25-19.6 3 Hz) delivered by flexiVent (Scireq, Montreal, PQ). Estimates of airway re sistance (Raw), inertance (I), and the coefficients of tissue damping (G(L) ) and tissue elastance (H-L) were obtained by fitting a model to each imped ance spectrum. Hysteresivity (eta) was calculated as G(L)/H-L. There was a significant increase in eta (P < 0.01) and a trend to a decrease in H-L (P = 0.07) of TGF-<alpha> mice compared with the wild-type group. There was no significant change in Raw, I, or G(L). Structural abnormality present in t he lungs of adult TGF-alpha mice alters viscoelastic coupling of the tissue s, as evidenced by a change in eta.