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

• Published in: Journal of applied physiology (1985) Vol. 106; no. 2; pp. 520 - 530
• Main Authors: Kaczka, David W, Brown, Robert H, Mitzner, Wayne
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01.02.2009; American Physiological Society
• Subjects: Airports; Airway management; Airway Resistance - drug effects; Animals; Biological and medical sciences; Bronchial Provocation Tests; Bronchoconstriction - drug effects; Bronchoconstrictor Agents - administration & dosage; Computed tomography; Dogs; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Heterogeneity; Infusions, Intravenous; Lung - diagnostic imaging; Lung - drug effects; Lung - physiology; Lung diseases; Methacholine Chloride - administration & dosage; Models, Biological; Oscillometry; Respiratory function; Respiratory Mechanics; Respiratory system; Tomography, X-Ray Computed; Fissipedia; Carnivora; canine; Respiratory system; resistance; Respiratory tract; Elastance; Vertebrata; Mammalia; parameter estimation; Dog; Akaike criterion; methacholine
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/japplphysiol.90576.2008

Departments of 1 Anesthesiology and Critical Care Medicine, 2 Biomedical Engineering, 3 Environmental Health Sciences, and 4 Radiology, The Johns Hopkins University, Baltimore, Maryland Submitted 27 April 2008 ; accepted in final form 8 October 2008 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. resistance; elastance; parameter estimation; Akaike criterion; canine; methacholine Address for reprint requests and other correspondence: D. W. Kaczka, Dept. of Anesthesiology and Critical Care Medicine, The Johns Hopkins Hospital, 600 North Wolfe St., Meyer 289, Baltimore, MD 21287 (e-mail: dkaczka1{at}jhmi.edu )