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Assessment of heterogeneous airway constriction in dogs: a structure-function analysis
Journal article   Open access   Peer reviewed

Assessment of heterogeneous airway constriction in dogs: a structure-function analysis

David W Kaczka, Robert H Brown and Wayne Mitzner
Journal of applied physiology (1985), Vol.106(2), pp.520-530
02/2009
DOI: 10.1152/japplphysiol.90576.2008
PMCID: PMC2644239
PMID: 18927269
url
https://doi.org/10.1152/japplphysiol.90576.2008View
Published (Version of record) Open Access

Abstract

Obstructive lung diseases are often characterized by heterogeneous patterns of bronchoconstriction, although specific relationships between structural heterogeneity and lung function have yet to be established. We measured respiratory input impedance (Zrs) in eight anesthetized dogs using broadband forced oscillations at baseline and during intravenous methacholine (MCh) infusion. We also obtained high-resolution computed tomographic (HRCT) scans in 4 dogs and identified 20-30 individual airway segments in each animal. The Zrs spectra and HRCT images were obtained before and 5 min following a deep inspiration (DI) to 35 cmH(2)O. Each Zrs spectrum was fitted with two different models of the respiratory system: 1) a lumped airways model consisting of a single airway compartment, and 2) a distributed airways model incorporating a continuous distribution of airway resistances. For the latter, we found that the mean level and spread of airway resistances increased with MCh dose. Whereas a DI had no effect on average airway resistance during MCh infusion, it did increase the level of airway heterogeneity. At baseline and low-to-moderate doses of MCh, the lumped airways model was statistically more appropriate to describe Zrs in the majority of dogs. At the highest doses of MCh, the distributed airways model provided a superior fit in half of the dogs. There was a significant correlation between heterogeneity assessed with inverse modeling and the standard deviation of airway diameters obtained from HRCT. These data demonstrate that increases in airway heterogeneity as assessed with forced oscillations and inverse modeling can be linked to specific structural alterations in airway diameters.
Airway Resistance - drug effects Bronchial Provocation Tests Tomography, X-Ray Computed Lung - diagnostic imaging Lung - physiology Dose-Response Relationship, Drug Bronchoconstrictor Agents - administration & dosage Animals Bronchoconstriction - drug effects Methacholine Chloride - administration & dosage Models, Biological Lung - drug effects Dogs Infusions, Intravenous Respiratory Mechanics Oscillometry

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