Effect of lung volume on interrupter resistance in cats challenged with methacholine

To examine the effects of changes in lung volume on the magnitude of maximal bronchoconstriction, seven anesthetized, paralyzed, tracheostomized cats were challenged with aerosolized methacholine (MCh) and respiratory system resistance (Rss) was measured at different lung volumes using the interrupter technique. Analysis of the pressure changes following end-inspiratory interruptions allowed us to partition Rss into two quantities with the units of resistance, one (Rinit) corresponding to the resistance of the airways and the other (Rdif) reflecting the viscoelastic properties of the tissues of the respiratory system as well as gas redistribution following interruption of flow. Rinit and Rdif were used to construct concentration-response curves to MCh. Lung volume was increased by the application of 5, 10, and 15 cmH2O of positive end-expiratory pressure. The curve for Rinit reached a plateau in all cats, demonstrating a limit to the degree of MCh-induced bronchoconstriction. The mean value of Rinit (cmH2O·ml-1·s) for the group under control conditions was 0.011 and rose to 0.058 after maximal bronchoconstriction; the volume a which the flow was interrupted was 11.5 ± 0.5 (SE) ml/kg above functional residual capacity (FRC). It then fell progressively to 0.029 at 21.2 ± 0.8 ml/kg above FRC, 0.007 at 35.9 ± 1.3 ml/kg above FRC, and 0.005 at 52.0 ± 1.8 ml/kg above FRC. Cutting either the sympathetic or parasympathetic branches of the vagi had no significant effect on the lung volume-induced changes in MCh-induced bronchoconstriction. These data support the hypothesis that the reduction in bronchoconstriction caused by increasing lung volume is related to an increase in the mechanical impedance to airway smooth muscle shortening and is not neurally mediated.