title: Differences in the pattern of bronchoconstriction induced by intravenous and inhaled methacholine in rabbit.
abstract: We measured bronchoconstriction in central bronchi, and in small peripheral airways causing the emergence of ventilation defects (VD), through two delivery routes: intravenous (IV) and inhaled MCh, in 2 groups of rabbits (A: n=5; B: n=4), using synchrotron imaging of regional lung structure and ventilation. We assessed the effect an initial IV challenge on a subsequent inhaled challenge in group B. Inhaled MCh decreased central airway cross-sections (CA) by 13-22%, but increased VD area by 25-49%. IV MCh decreased CA by 44% but increased the area of ventilation defects (VD) by 13% only. An initial IV MCh challenge reduced regional ventilation heterogeneity following a subsequent inhaled MCh challenge, suggesting the role of agonist-receptor interaction in the response pattern. Heterogeneous agonist distribution due to uneven aerosol deposition could explain the different patterns of response between IV and inhaled routes. This mechanism could participate in the emergence of ventilation heterogeneities during bronchial challenge, or exposure to allergen in asthmatic patients.
authors.affiliation: Department of Physics, University of Helsinki, Finland. Electronic address: satu.strengell@helsinki.fi.
authors.forename: Satu
authors.initials: S
authors.lastname: Strengell
authors.forename: Liisa
authors.initials: L
authors.lastname: Porra
authors.forename: Anssi
authors.initials: A
authors.lastname: Sovijärvi
authors.forename: Heikki
authors.initials: H
authors.lastname: Suhonen
authors.forename: Pekka
authors.initials: P
authors.lastname: Suortti
authors.forename: Sam
authors.initials: S
authors.lastname: Bayat
mesh_terms: D000280:Administration, Inhalation; D061605:Administration, Intravenous; D000704:Analysis of Variance; D000818:Animals; D001980:Bronchi / Q000098:blood supply / Q000187:drug effects; D016084:Bronchoconstriction / Q000187:drug effects*; D008168:Lung / Q000000981:diagnostic imaging / Q000187:drug effects; D008297:Male; D016210:Methacholine Chloride / Q000008:administration & dosage*; D018721:Muscarinic Agonists / Q000008:administration & dosage*; D012123:Pulmonary Ventilation / Q000187:drug effects*; D011817:Rabbits; D011859:Radiography; D015898:Tomography Scanners, X-Ray Computed; D014978:Xenon
chemical_list: D018721:Muscarinic Agonists; D016210:Methacholine Chloride; D014978:Xenon
keywords: Asthma; Bronchial responsiveness; Computed tomography; Regional lung ventilation; Synchrotron; Xenon