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J Appl Physiol 104: 1601-1610, 2008. First published April 17, 2008; doi:10.1152/japplphysiol.01207.2007
8750-7587/08 $8.00
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Computational assessment of airway wall stiffness in vivo in allergically inflamed mouse models of asthma

Ana Cojocaru, Charles G. Irvin, Hans C. Haverkamp, and Jason H. T. Bates

Vermont Lung Center, University of Vermont College of Medicine, Burlington, Vermont

Submitted 12 November 2007 ; accepted in final form 11 April 2008

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.

airway resistance; airways hyperresponsiveness; airway smooth muscle; airway remodeling


Address for reprint requests and other correspondence: J. H. T. Bates, HSRF 228, 149 Beaumont Ave., Burlington, VT 05405-0075 (e-mail: jason.h.bates{at}uvm.edu)






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