Effect of Stochastic Heterogeneity on Lung Impedance During Acute Bronchoconstriction: a Model Analysis

In a previous study (J. H. T. Bates, A. M. Lauzon, G. S. Dechman, G. N. Makaym, and T. F. Schuessler. J. Appl. Physiol. 76: 616-626, 1994), we investigated the acute changes in isovolume lung mechanics immediately after a bolus injection of histamine. We found that dynamic resistance and elastance increased progressively in the 80-s period after injection, whereas the estimated tissue hysteresivity reached a stable plateau after approximately 25 s. In the present study, we developed a computer model of the lung to investigate the mechanisms responsible for these observations. The model conforms to Horsfield's morphometry, with the addition of compliant airways and structural damping tissue units. Using this model, we simulated the time course of acute bronchoconstriction after intravenous administration of a bolus of bronchial agonist. Heterogeneity was induced by randomly varying the values of the maximal airway smooth muscle contraction and the tissue response to the agonist. Our results demonstrate that much of the increase in lung impedance observed in our previous study can be produced purely by the effects of airway heterogeneity. However, we were only able to reproduce the plateauing of hysteresivity by assigning a minimum radius to each airway, beyond which it would immediately snap completely shut. We propose that airway closure played an important role in our experimental observations.