MODELING THE DYNAMICS OF AIRWAY CONSTRICTION: EFFECTS OF AGONIST TRANSPORT AND BINDING

Amin, Samir D; Majumdar, Arnab; Frey, Urs; Suki, Bela (2010). MODELING THE DYNAMICS OF AIRWAY CONSTRICTION: EFFECTS OF AGONIST TRANSPORT AND BINDING. Journal of applied physiology, 109(2), pp. 553-563. Bethesda, Md.: American Physiological Society 10.1152/japplphysiol.01111.2009

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Recent advances have revealed that during exogenous airway challenge, airway diameters can not be adequately predicted by their initial diameters. Furthermore, airway diameters can also vary greatly in time on scales shorter than a breath. In order to better understand these phenomena, we developed a multiscale model which allows us to simulate aerosol challenge in the airways during ventilation. The model incorporates agonist-receptor binding kinetics to govern the temporal response of airway smooth muscle (ASM) contraction on individual airway segments, which together with airway wall mechanics, determines local airway caliber. Global agonist transport and deposition is coupled with pressure-driven flow, linking local airway constrictions with global flow dynamics. During the course of challenge, airway constriction alters the flow pattern, redistributing agonist to less constricted regions. This results in a negative feedback which may be a protective property of the normal lung. As a consequence, repetitive challenge can cause spatial constriction patterns to evolve in time, resulting in a loss of predictability of airway diameters. Additionally, the model offers new insight into several phenomena including the intra- and inter-breath dynamics of airway constriction throughout the tree structure.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Frey, Urs Peter

ISSN:

8750-7587

Publisher:

American Physiological Society

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:07

Last Modified:

08 Jun 2016 10:19

Publisher DOI:

10.1152/japplphysiol.01111.2009

PubMed ID:

20507971

Web of Science ID:

000280758800037

URI:

https://boris.unibe.ch/id/eprint/164 (FactScience: 196595)

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