The Bronchial Response, but not the Pulmonary Response to Inhaled Methacholine Is Dependent on the Aerosol Deposition Pattern: Conclusion
Similarly, collateral ventilation may also be more effective at a segmental level than when a whole lobe is obstructed, at least in the dog Our findings further support the previously reported discrepancy in time courses of Va/Q mismatch and bronchial constriction, and the discrepancy occurred independently of whether the aerosol was deposited in the central or in the distal airways. Taking these data together, different mechanisms of the methacholine-induced bronchoconstriction and responses of the gas exchanging elements may be suggested. buy ventolin inhaler
It is conceivable that change in airway muscle contraction is a prominent event in the central airways, while the response in peripheral airways may be more related to mucosal and interstitial edema. However, smooth muscle constriction of the central airways alone produces only relatively modest increases in the resistance of the airways. When constriction is coupled with airway wall thickening, however, dramatic increases in resistance may result from relatively minor degrees of smooth muscle contraction. Apart from the fact that measurements of effects elicited in various sections of the airways may differ depending on the responses of the various target organs, a generalized edema within the airway mucosa, as a response to inhaled methacholine, may elicit different responses along the bronchial tree. We propose that a generalized edema throughout the bronchial tree, as well as smooth muscle contraction of the central airway wall, may explain some of the recorded effects.
Generally, receptor-induced responses are likely to be dose dependent within a certain dose range. However, we did not find the responses of gas exchange to be related to the suggested differences in doses, a finding that may suggest that additional events with different time courses interfere with the pharmacologically induced effects. Acetylcholine and histamine are capable of releasing nitric oxide (NO) from the endothelium, and NO-related molecules have been shown to mediate pulmonary vasodilation. Methacholine is also known to have pronounced vasoactive effects, and potentially NOmediated vascular responses could explain some of the effects recorded in our experiment, and in accordance, enhanced bronchial circulation has been shown after local deposition of methacholine in the trachea of dogs. The subepithelial microvasculature of the airways in dogs or man is perfused with blood from vessels located deep in the thick airway walls of trachea and its larger branches, whereas in the thin-walled peripheral bronchi, anastomoses between the bronchial and the pulmonary circulation constitute the source of micro vascular perfusion.