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research-article

Transition from phasic to tonic contractility in airway smooth muscle after birth: an experimental and computational modelling study

[+] Author and Article Information
Kimberley Wang

School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia; Telethon Kids Institute, The University of Western Australia, Perth, Western Australia, Australia
kimberley.wang@uwa.edu.au

Amy Y Chang

School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia
kimo855@hotmail.com

J Jane Pillow

School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia; Centre for Neonatal Research and Education, Medical School, The University of Western Australia, Perth, Western Australia, Australia; King Edward Memorial Hospital, Subiaco, Western Australia, Australia
jane.pillow@uwa.edu.au

Bela Suki

Department of Biomedical Engineering, Boston University, Boston, Massachusetts, USA
bsuki@bu.edu

Peter Noble

School of Human Sciences, The University of Western Australia, Crawley, Western Australia, Australia; Centre for Neonatal Research and Education, Medical School, The University of Western Australia, Perth, Western Australia, Australia
peter.noble@uwa.edu.au

1Corresponding author.

ASME doi:10.1115/1.4042312 History: Received August 29, 2018; Revised December 11, 2018

Abstract

Fetal airway smooth muscle (ASM) exhibits phasic contractile behaviour, which transitions to a more sustained 'tonic' contraction after birth. The timing and underlying mechanisms of ASM transition from a phasic to tonic contractile phenotype are yet to be established. We characterised phasic ASM contraction in preterm (128 d gestation), term (~150 d gestation), 1 - 4 month, 1 year and adult sheep. Spontaneous phasic activity was measured in bronchial segments as amplitude, frequency and intensity. The mechanism of phasic ASM contraction was investigated further with a computational model of ASM force development and lumen narrowing. The computational model comprised a 2D cylindrical geometry of a network of contractile units and activation of neighbouring cells was dependent on the strength of coupling between cells. As expected, phasic contractions were most prominent in fetal airways and decreased with advancing age, to a level similar to the level in the 1 - 4 month lambs. Computational predictions demonstrated phasic contraction through the generation of a wave of activation events, the magnitude of which is determined by the number of active cells and the strength of cell-cell interactions. Decreases in phasic contraction with advancing age were simulated by reducing cell-cell coupling. Results show that phasic activity is suppressed rapidly after birth, then sustained at a lower intensity from the pre-weaning phase until adulthood in an ovine developmental model. Cell-cell coupling is proposed as a key determinant of phasic ASM contraction and if reduced could explain the observed maturational changes.

Copyright (c) 2018 by ASME
Topics: Modeling , Muscle , Waves , Geometry
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