Computational assessment of airway wall stiffness in vivo in allergically inflamed mouse models of asthma

J Appl Physiol (1985). 2008 Jun;104(6):1601-10. doi: 10.1152/japplphysiol.01207.2007. Epub 2008 Apr 17.

Abstract

Allergic inflammation is known to cause airway hyperresponsiveness in mice. However, it is not known whether inflammation affects the stiffness of the airway wall, which would alter the load against which the circumscribing smooth muscle shortens when activated. Accordingly, we measured the time course of airway resistance immediately following intravenous methacholine injection in acutely and chronically allergically inflamed mice. We estimated the effective stiffness of the airway wall in these animals by fitting to the airway resistance profiles a computational model of a dynamically narrowing airway embedded in elastic parenchyma. Effective airway wall stiffness was estimated from the model fit and was found not to change from control in either the acute or chronic inflammatory groups. However, the acutely inflamed mice were hyperresponsive compared with controls, which we interpret as reflecting increased delivery of methacholine to the airway smooth muscle through a leaky pulmonary endothelium. These results support the notion that acutely inflamed BALB/c mice represent an animal model of functionally normal airway smooth muscle in a transiently abnormal lung.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Airway Resistance*
  • Allergens
  • Animals
  • Asthma / immunology
  • Asthma / physiopathology*
  • Bronchial Hyperreactivity / immunology
  • Bronchial Hyperreactivity / physiopathology*
  • Bronchial Provocation Tests
  • Bronchoconstrictor Agents / administration & dosage
  • Computer Simulation*
  • Disease Models, Animal
  • Elasticity
  • Female
  • Inflammation / immunology
  • Inflammation / physiopathology*
  • Injections, Intravenous
  • Methacholine Chloride / administration & dosage
  • Mice
  • Mice, Inbred BALB C
  • Models, Biological*
  • Ovalbumin
  • Time Factors

Substances

  • Allergens
  • Bronchoconstrictor Agents
  • Methacholine Chloride
  • Ovalbumin