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J Appl Physiol 91: 2730-2734, 2001;
8750-7587/01 $5.00
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Vol. 91, Issue 6, 2730-2734, December 2001

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

Jane J. Pillow1,2, Thomas R. Korfhagen3, Machiko Ikegami3, and Peter D. Sly1,2,4

1 TVW Telethon Institute for Child Health Research, West Perth 6872; 2 King Edward and Princess Margaret Hospital, Perth 6840; 4 Department of Paediatrics, University of Western Australia, Subiaco 6008, WA, Australia; and 3 Division of Pulmonary Biology, Children's Hospital Medical Centre, Cincinnati, Ohio 45229-3039

Increased transforming growth factor (TGF)-alpha has been observed in neonatal chronic lung disease. Lungs of transgenic mice that overexpress TGF-alpha 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-alpha 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 (eta ) was calculated as GL/HL. There was a significant increase in eta  (P < 0.01) and a trend to a decrease in HL (P = 0.07) of TGF-alpha 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-alpha mice alters viscoelastic coupling of the tissues, as evidenced by a change in eta .

pulmonary fibrosis; respiratory mechanics; forced oscillation technique; transforming growth factor-alpha


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