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

Increased transforming growth factor (TGF)-α has been observed in neonatal chronic lung disease. Lungs of transgenic mice that overexpress TGF-α develop enlarged air spaces and pulmonary fibrosis compared with wild-type mice. We hypothesized that these pathological changes may alter the mechanical coupling of viscous and elastic forces within lung parenchyma. Respiratory impedance was measured in open-chested, tracheostomized adult wild-type and TGF-α mice by using the forced oscillation technique (0.25–19.63 Hz) delivered by flexiVent (Scireq, Montreal, PQ). Estimates of airway resistance (Raw), inertance (I), and the coefficients of tissue damping (GL) and tissue elastance ( HL) were obtained by fitting a model to each impedance spectrum. Hysteresivity (η) was calculated as GL/ HL. There was a significant increase in η ( P < 0.01) and a trend to a decrease in HL( P = 0.07) of TGF-α mice compared with the wild-type group. There was no significant change in Raw, I, or GL. Structural abnormality present in the lungs of adult TGF-α mice alters viscoelastic coupling of the tissues, as evidenced by a change in η.