Bronchodilatory effect of deep inspiration on the dynamics of bronchoconstriction in mice

We recently developed a computational model of an airway embedded in elastic parenchyma ( Bates JH, Lauzon AM. J Appl Physiol 102: 1912 - 1920, 2007) that accurately mimics the time dependence of airway resistance on tidal volume and positive end- expiratory pressure ( PEEP) following methacholine injection in normal animals. In the present study, we compared the model predictions of bronchodilation induced by a deep inflation ( DI) of the lung following administration of the bronchial agonist methacholine to corresponding experimental measurements made in mice. We found that a DI in mice caused an immediate reduction in airway resistance when it was administered soon after intravenous injection of methacholine, while the airway smooth muscle was in the process of contracting. However, the magnitude of the reduction in resistance was greater and its subsequent rate of increase less than that predicted by the model. We found that this effect was most pronounced when the DI was given within similar to 3 s following methacholine injection, again in contrast to the predictions of the model. The reduction of airway resistance was virtually independent of the rate of lung inflation during the DI, however, which agrees with model predictions. We conclude that while the model accounts for a substantial fraction of the post- DI reduction in airway resistance seen experimentally, there remain important differences between prediction and experiment that suggest that the effects of a DI are not simply due to eccentric contraction of the airway smooth muscle.