Effect of stochastic heterogeneity on lung impedance  during acute bronchoconstriction: a model analysis

Thorpe, C. William; Bates, Jason H. T.

doi:10.1152/jappl.1997.82.5.1616

Cited by 120 publications

(110 citation statements)

References 36 publications

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“…This neglects all of the heterogeneity among airways of different sizes and generations that is known to characterize the lung, and it makes numerous simplifying assumptions about the dynamics of ASM contraction and parenchymal mechanics (5). It also assumes a particularly simple mathematical form for the stiffness of the airway wall (35), which is certain to be a gross oversimplification of reality. Indeed, our laboratory recently showed that, even though this model accounts for much of the transient dynamics in R following a deep lung inflation in constricted mice (3), there appears to be significant effects due to tissue viscoelasticity in these dynamics for which the model does not account.…”

Section: Discussionmentioning

confidence: 99%

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

Cojocaru

Irvin²,

Haverkamp³

et al. 2008

Journal of Applied Physiology

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Cojocaru A, Irvin CG, Haverkamp HC, Bates JH. Computational assessment of airway wall stiffness in vivo in allergically inflamed mouse models of asthma. J Appl Physiol 104: 1601-1610, 2008. First published April 17, 2008 doi:10.1152/japplphysiol.01207.2007.-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 AIRWAY REMODELING HAS BEEN shown to occur in asthma, but there is little consensus as to whether or not remodeling impacts airways hyperresponsiveness (AHR) (8,21,25,33,34). On the one hand, remodeling of the airway wall might make it stiffer than normal, which would be expected to limit the extent to which it can be narrowed by activation of airway smooth muscle (ASM). On the other hand, remodeled airway walls also tend to be thicker than normal, which could geometrically amplify the luminal narrowing caused by a given degree of smooth muscle shortening. This richness of possibilities makes the mechanical effects of airway remodeling a fruitful area for theory and speculation (1), but complicates its experimental elucidation.Our laboratory recently developed a computational model of a single airway contracting against the elastic tethering forces of the parenchyma in which it is embedded (5). We showed that this model accurately describes the effects of positive end-expiratory pressure (PEEP) and tidal volume on airway responsiveness in normal animals and also explains much of the effect on airway resistance (Raw) caused by a deep inflation in constricted mice (3), provided the model includes a parameter to account for the stiffness of the airway wall. Thus, by fitting this model to continuous measurements of Raw made at different lung volumes following a bolus injection of bronchial agonist, we can estimate the effective stiffness of the airway wall in vivo. In the present study, we use this approach to inve...

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Section: Discussionmentioning

confidence: 99%

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

Cojocaru

Irvin²,

Haverkamp³

et al. 2008

Journal of Applied Physiology

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“…We adapted a recently developed model for the analysis of the time course of acinar flow and pressure during MV (21). The model is based on the branching network proposed for the human lungs by Horsfield et al (15), and it is a careful simplification of previously published computational models of lung mechanics in the frequency domain (14,30). Briefly, the Horsfield airway tree is an asymmetric bifurcating network with 35 orders.…”

Section: Methodsmentioning

confidence: 99%

“…Order 35 corresponds to the trachea. Therefore, the conducting airways are orders , whereas airway orders 1-7 represent the pulmonary acini (30). In our model, each airway is represented by a combination of laminar resistance and wall compliance (Fig.…”

Section: Methodsmentioning

confidence: 99%

Modeling airflow-related shear stress during heterogeneous constriction and mechanical ventilation

Nucci

Suki²,

Lutchen³

2003

Journal of Applied Physiology

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Nucci, Gianluca, Bé la Suki, and Kenneth Lutchen. Modeling airflow-related shear stress during heterogeneous constriction and mechanical ventilation. J Appl Physiol 95: 348-356, 2003. First published March 21, 2003 10.1152/ japplphysiol.01179.2001.-Ventilator-induced lung injury has been proposed as being caused by overdistention and closure and reopening of small airways and alveoli. Here we investigate the possibility that heterogeneous constriction increases airflow-related shear stress to a dangerously high level that may be sufficient to cause injury to the epithelial cells during mechanical ventilation. We employed an anatomically consistent model of the respiratory system, based on Horsfield morphometric data, and solved for the time evolution of pressure and flow along the airway tree during mechanical ventilation. We simulated constant-flow ventilation with passive expiration in two different conditions: baseline and highly heterogeneous constriction. The constriction was applied with two strategies: establishing a simple diameter reduction or adding also a length shortening. The shear stress distribution on airway walls was analyzed for airways ranging from the trachea to the acini. Our results indicate that 1) heterogeneous constriction can amplify the maximal values of shear stress up to 50-fold, with peak values higher than 0.6 cmH 2O; 2) the highest shear stress is found in pathways constricted by 60-80%; 3) simultaneous diameter reduction and shortening amplifies the shear stresses by three-to fourfold, with shear stresses reaching 2 cmH 2O; and 4) there is a range of airways (diameters from 0.6 to 0.3 mm at baseline) that appear to be at risk of very high stresses. We conclude that elevated airflow-related shear stress on the epithelial cell layer can occur during heterogeneous constriction and conjecture that this may constitute a mechanism contributing to ventilator-induced lung injury. lung mechanics; ventilator-induced lung injury; simulation model MECHANICAL VENTILATION (MV) is often required to manage patients with acute respiratory failure (ARF) of different origins, including those associated with abnormalities in respiratory mechanics (31). However, there is considerable experimental evidence that MV itself can also cause or exacerbate lung injury, resulting in so-called ventilator-induced lung injury (VILI) (9,23,28). The mechanisms associated with VILI have not yet been fully elucidated. Two mechanisms have received the most attention. One is related to high airway pressures during MV, termed barotrauma, causing excessive overdistension of alveolar structures (26). More recently, it has become evident that injury results more from overstretching the alveolar tissues than from high pressures, and hence it is now termed volutrauma (10). Another potential mechanism is the repeated recruitment and derecruitment of atelectatic lung units (28). In principle, opening a collapsed airway would require very high-pressure drops across the fluid plug blocking the airway (13). During the process o...

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“…This question has been addressed in two recent studies investigating the contribution of heterogeneity to the increase in pulmonary impedance in response to bronchoconstrictive agonists [23,24]. In both instances, the authors used the Horsfield asymmetric airway tree and computational models to determine lung resistance and elastance.…”

Section: Mathematical Models Of Airway Narrowingmentioning

confidence: 99%

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

2000

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Airway hyperresponsiveness (AHR), the exaggerated response to constrictor agonists in asthmatic subjects, is incompletely understood. Changes in either the quantity or properties of airway smooth muscle (ASM) are possible explanations for AHR. Morphometric analyses demonstrate structural changes in asthmatic airways, including subepithelial fibrosis, gland hyperplasia/hypertrophy, neovascularization and an increase in ASM mass.Mathematical modelling of airway narrowing suggests that, of all the changes in structure, the increase in ASM mass is the most probable cause of AHR. An increase in ASM mass in the large airways is more closely associated with a greater likelihood of dying from asthma than increases in ASM mass in other locations within the airway tree. ASM contraction is opposed by the elastic recoil of the lungs and airways, which appears to limit the degree of bronchoconstriction in vivo. The cyclical nature of tidal breathing applies stresses to the airway wall that enhance the bronchodilating influence of the lung tissues on the contracting ASM, in all probability by disrupting cross-bridges. However, the increase in ASM mass in asthma may overcome the limitation resulting from the impedances to ASM shortening imposed by the lung parenchyma and airway wall tissues. Additionally, ASM with the capacity to shorten rapidly may achieve shorter lengths and cause a greater degree of bronchoconstriction when stimulated to contract than slower ASM.Changes in ASM properties are induced by the process of sensitization and allergen-exposure such as enhancement of phospholipase C activity and inositol phosphate turnover, and increases in myosin light chain kinase activity. Whether changes in ASM mass or biochemical/biomechanical properties form the basis for asthma remains to be determined. Eur Respir J 2000; 16: 349±354.

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Effect of stochastic heterogeneity on lung impedance during acute bronchoconstriction: a model analysis

Cited by 120 publications

References 36 publications

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

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

Modeling airflow-related shear stress during heterogeneous constriction and mechanical ventilation

The contribution of airway smooth muscle to airway narrowing and airway hyperresponsiveness in disease

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