Kinetics of respiratory system elastance after airway challenge in dogs

1 Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada H2X 2P2; and 2 Vermont Lung Center, The University of Vermont, Burlington, Vermont 05446 We compared the time courses of lung mechanical changes with intravenous (iv) injection vs. aerosol administration of histamine, methacholine, and ACh in dogs. We interpret these results in terms of a spring-and-dashpot model of airway smooth muscle receiving activation via a tissue compartment when agonist is delivered by the iv route and through an additional airway wall compartment when it is delivered by the aerosol route. The model accurately accounts for the principal features of the respiratory system elastance response curves. It also accounts for the differences between iv and aerosol responses, supporting the notion that agonist delivered by aerosol has to traverse a longer pathway to the airway smooth muscle than does agonist delivered iv. The time constants representing diffusive exchange of agonist between compartments were not significantly different for the three agonists, suggesting that the three agonists shared a common principal means of clearance, which was presumably blood flow. histamine; methacholine; acetylcholine; pulmonary blood flow; bronchial blood flow; pharmacokinetics