Tissue heterogeneity in the mouse lung: effects of elastase treatment

• Published in: Journal of applied physiology (1985) Vol. 97; no. 1; pp. 204 - 212
• Main Authors: Ito, Satoru, Ingenito, Edward P, Arold, Stephen P, Parameswaran, Harikrishnan, Tgavalekos, Nora T, Lutchen, Kenneth R, Suki, Bela
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.07.2004; American Physiological Society
• Subjects: Airway Resistance - drug effects; Algorithms; Animals; Biological and medical sciences; Biomechanical Phenomena; Coefficient of variation; Computer Simulation; Effects; Elasticity - drug effects; Emphysema; Enzymes; Fundamental and applied biological sciences. Psychology; Heterogeneity; Linear Models; Lung - drug effects; Lungs; Medical treatment; Mice; Mice, Inbred C57BL; Pancreatic Elastase - pharmacology; Positive-Pressure Respiration; Pulmonary Alveoli - drug effects; Pulmonary Alveoli - physiology; Respiration, Artificial; Respiratory Mechanics - drug effects; Respiratory system; Rodents; Swine; Tissues; Ventilation; Heterogeneity; Tissue; Vertebrata; Mammalia; Treatment; Mouse; Lung; Rodentia; Respiratory system
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.01246.2003

1 Department of Biomedical Engineering, Boston University, and 2 Division 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 ).