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Static and dynamic stress heterogeneity in a multiscale model of the asthmatic airway wall

Hiorns, Jonathan E.; Jensen, Oliver E.; Brook, Bindi S.

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Authors

Jonathan E. Hiorns

Oliver E. Jensen

Bindi S. Brook



Abstract

Airway hyperresponsiveness (AHR) is a key characteristic of asthma that remains poorly understood. Tidal breathing and deep inspiration ordinarily cause rapid relaxation of airway smooth muscle (ASM) (as demonstrated via application of length fluctuations to tissue strips) and are therefore implicated in modulation of AHR, but in some cases (such as application of transmural pressure oscillations to isolated intact airways) this mechanism fails. Here we use a multiscale biomechanical model for intact airways that incorporates strain stiffening due to collagen recruitment and dynamic force generation by ASM cells to show that the geometry of the airway, together with interplay between dynamic active and passive forces, gives rise to large stress and compliance heterogeneities across the airway wall that are absent in tissue strips. We show further that these stress heterogeneities result in auxotonic loading conditions that are currently not replicated in tissue-strip experiments; stresses in the strip are similar to hoop stress only at the outer airway wall and are under- or overestimates of stresses at the lumen. Taken together these results suggest that a previously underappreciated factor, stress heterogeneities within the airway wall and consequent ASM cellular response to this micromechanical environment, could contribute to AHR and should be explored further both theoretically and experimentally.

Journal Article Type Article
Acceptance Date May 15, 2016
Online Publication Date May 19, 2016
Publication Date Jul 1, 2016
Deposit Date Oct 12, 2016
Publicly Available Date Oct 12, 2016
Journal Journal of Applied Physiology
Print ISSN 8750-7587
Electronic ISSN 1522-1601
Publisher American Physiological Society
Peer Reviewed Peer Reviewed
Volume 121
Issue 1
Pages 233-247
DOI https://doi.org/10.1152/japplphysiol.00715.2015
Keywords airway hyperresponsiveness; circumferential stress; extracellular matrix; tidal breathing; deep inspirations
Public URL https://nottingham-repository.worktribe.com/output/792037
Publisher URL http://jap.physiology.org/content/121/1/233

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