Abstract 1861 Neonatal Pulmonology I: Mechanical Influences on Lung Development Platform, Tuesday, 5/4

Studies utilizing animal models of abnormal lung development may provide useful insights for the detailed measurement and interpretation of lung mechanics in the newborn infant with respiratory distress. Increased transforming growth factor-alpha (TGFα) has been observed in airway epithelial cells of infants with bronchopulmonary dysplasia. The lungs of transgenic mice that overexpress TGFα under the control of the surfactant protein C promoter, develop enlarged airspaces and pulmonary fibrosis. Pressure-volume curves on the excised lungs show increased specific compliance compared to wild-type mice. We hypothesized that these pathological changes may alter the mechanical coupling of the lung parenchyma, evident as an abnormal hysteresivity (η). The assessment of η necessitates the use of measurement techniques that partition the airway and tissue compartments. Methods: We used the forced oscillation technique (FOT) (pseudorandom non-integer multiple signal, 0.25 - 19.63 Hz) delivered by the Flexivent (Scireq, Can) to measure the respiratory system impedance in tracheostomized open-chested will-type and TGFα mice. The constant-phase model was fitted to each impedance spectrum, obtaining an airway resistance (Raw), inertance, and a frequency-dependent tissue resistance (Grs) and tissue elastance (Hrs). Hysteresivity was calculated as G/H. All parameters were corrected for body weight. The groups were compared using Student's t-test. Results: Model parameters are expressed as mean (±SE). There was negligible inertance. (Table)

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Conclusions: The recent application of the constant-phase model to analyse impedance spectra obtained using the low-frequency FOT allows non-invasive partitioned measurements of the mechanical parameters of the respiratory system. The presence of structural lung disease alters the mechanical coupling of the tissues, as evidenced by a change in η. Hysteresivity might be a useful index of structural integrity in the neonatal lung, where respiratory disease is predominantly parenchymal in nature.

Supported by: NHMRC Australia, NIH 5P50HL56387