Histamine aerosols were administered to nine anesthetized, paralyzed, mechanically ventilated mongrel dogs with the cervical vagi first intact, then sectioned, and then peripherally stimulated at two intensities. Pulmonary resistance (RL) was measured, and dose-response curves were constructed in the four conditions. All dogs had dose-related increases in RL with increasing histamine aerosol concentrations. After the vagi were cut, the degree to which constant levels of vagal stimulation altered the dose-response relationships was assessed by examining the slopes and positions of the RL vs. histamine curves. Four of the nine animals studied showed evidence of increasing vagal efferent activity as the concentration of histamine in the aerosol increased, but three did not. Two of the dogs had equivocal responses in that increasing activity was suggested but not clearly demonstrated. These results indicate that, in addition to direct effects of histamine, the extent of and basis for vagal interaction with this stimulus varies among dogs. The results suggest that the basis of vagal interaction is related to either constant efferent activity (tone) or increasing efferent activity (reflexes).
To determine the relationship between changes in density dependence of maximal expiratory flow and changes in the predominant site of bronchoconstriction, we altered the pattern of inhalation of a methacholine aerosol to achieve deposition either centrally (by short choppy breaths) or peripherally (by slow deep breaths). Partial expiratory flow volume curves on air and on 80% helium-20% oxygen (HeO2) were recorded in six healthy subjects before and after each pattern of methacholine inhalation. We varied concentrations of methacholine and number of inhalations to achieve equivalent degrees of bronchoconstriction as assessed by decreases in maximal flow (Vmax) on air, which fell 27% from control values. Vmax on HeO2 also fell after both inhalation patterns. Density dependence (Vmax on HeO2 divided by Vmax on air) decreased following slow deep breaths of bronchoconstrictor aerosol, and increased following short choppy breaths. In three subjects, inhalation of radiolabeled methacholine aerosol confirmed that the slow deep pattern was associated with a diffuse, more peripheral deposition, whereas the short choppy pattern led to central deposition. We conclude that changes in density dependence reflect the predominant site of obstruction after acute methacholine aerosol challenge in healthy subjects.
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