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J Appl Physiol 97: 204-212, 2004. First published March 12, 2004; doi:10.1152/japplphysiol.01246.2003
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Tissue heterogeneity in the mouse lung: effects of elastase treatment

Satoru Ito,1 Edward P. Ingenito,2 Stephen P. Arold,1 Harikrishnan Parameswaran,1 Nora T. Tgavalekos,1 Kenneth R. Lutchen,1 and Béla Suki1

1Department of Biomedical Engineering, Boston University, and 2Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115

Submitted 20 November 2003 ; accepted in final form 8 March 2004

We developed a network model in an attempt to characterize heterogeneity of tissue elasticity of the lung. The model includes a parallel set of pathways, each consisting of an airway resistance, an airway inertance, and a tissue element connected in series. The airway resistance, airway inertance, and the hysteresivity of the tissue elements were the same in each pathway, whereas the tissue elastance (H) followed a hyperbolic distribution between a minimum and maximum. To test the model, we measured the input impedance of the respiratory system of ventilated normal and emphysematous C57BL/6 mice in closed chest condition at four levels of positive end-expiratory pressures. Mild emphysema was developed by nebulized porcine pancreatic elastase (PPE) (30 IU/day x 6 days). Respiratory mechanics were studied 3 wk following the initial treatment. The model significantly improved the fitting error compared with a single-compartment model. The PPE treatment was associated with an increase in mean alveolar diameter and a decrease in minimum, maximum, and mean H. The coefficient of variation of H was significantly larger in emphysema (40%) than that in control (32%). These results indicate that PPE treatment resulted in increased time-constant inequalities associated with a wider distribution of H. The heterogeneity of alveolar size (diameters and area) was also larger in emphysema, suggesting that the model-based tissue elastance heterogeneity may reflect the underlying heterogeneity of the alveolar structure.

elastance; emphysema; modeling; distribution



Address for reprint requests and other correspondence: B. Suki, Dept. of Biomedical Engineering, Boston Univ., 44 Cummington St., Boston, MA 02215 (E-mail: bsuki{at}bu.edu).




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