Airway Smooth Muscle and Airway Wall Coupled Dynamics
Airway Smooth Muscle and Airway Wall Coupled Dynamics

Author: Anand K. Rampadarath

Publisher:

Published: 2018

Total Pages: 101

ISBN-13:

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Primarily, asthma is a disease of reversible airway constriction which is characterized by airways that constrict too easily and too much. These processes are modulated via a layer of airway smooth muscle (ASM) which surrounds each airway in the lung, wherein its activation leads to airway narrowing and potentially, closure. As a result, understanding the interaction between the ASM and the airway wall is crucial to understanding the reversible airway obstruction central to asthma. Although cross-bridge theory is a well-studied representation of complex smooth muscle dynamics, and can be coupled to the airway wall, this comes at significant computational cost, even for isolated airways. Because many phenomena of interest in pulmonary physiology cannot be adequately understood by studying isolated airways, this presents a significant limitation.We present a distribution moment (DM) approximation for the coupled system consisting of the ASM and the airway wall. Specifically, we first derive a reduced DM system for the cross-bridge theory which capture the macroscopic characteristics of the original full ASM theory. We then study the validity of the reduced coupled system when the airway is subjected to periodic pressure oscillations and show that in most cases, the DM system is valid. We also explore the region of breakdown. These results show that in many situations within physiological ranges, the DM approximation provides an orders-of-magnitude reduction in computational complexity relative to the full cross-bridge-airway coupled system. Deep inspirations (DI) are a widely studied topic due to their varied effectiveness as a bronchodilator in asthmatic and non-asthmatic patients. Specifically, it is known to be effective at reversing bronchoconstriction in non-asthmatic patients but may fail to prevent bronchoconstriction in asthmatic patients. Inspired by a recent study on the effect of deep inspirations on the rate of re-narrowing of an isolated airway, we investigate whether latch-bridge dynamics of the cross-bridge theory, coupled with non-linear compliance of the airway wall, can fully account for the reported results. We develop and present length-and pressure-controlled protocols which mimic both the experiments performed in the study, as well as simulate in vivo conditions respectively. The protocols are modelled using the DM approximation and show qualitative agreement with the results reported by the experiments, suggesting that latch-bridge dynamics coupled with airway wall non-compliance is sufficient to explain these results. As a secondary study, we also show that the DM approximated method is a suitable method to further investigate DIs on isolated (or branched) airways, as it is both qualitatively and quantitatively similar to the full cross-bridge model under equivalent conditions, and is less computationally intensive than traditional methods. We also study clustered ventilation defects, which are a hallmark of asthma characterized by the emergence of spatially organised regions of hypo- and hyper-ventilated airways.These regions (clusters) can vary from event to event and as such are considered to be partially dynamic rather than purely structural. We investigate these defects by incorporating rich ASM dynamics to systems of symmetrically branched coupled airways via the DM method, and compare the qualitative and quantitative behaviour of this system to a full ASM model, as well as to a simplified ASM model. We study the distribution of clusters of closed airways as a result of randomly perturbed initial airway radii for increasing ASM activation at static pressures. Our results show that the inclusion of rich ASM dynamics via the DM approximation leads to clustering distributions that are qualitatively similar to the highly simplified model as well as to the full ASM model. We also show that the DM model is less computationally intensive for both large and small numbers of coupled branched airways, and suggests that this model represents a viable option for the inclusion of rich ASM dynamics in whole lung models in future studies.

Airway Smooth Muscle in Health and Disease
Airway Smooth Muscle in Health and Disease

Author: R.F. Coburn

Publisher: Springer Science & Business Media

Published: 2012-12-06

Total Pages: 325

ISBN-13: 1461307791

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I organized this book because there is a need to put together in book form recent advances in our knowledge of how airway smooth muscle:works in health and in disease. After a period when it seemed that progress was very slow, there has been in the past few years an incredibly rapid gathering of knowledge in this area. In particular, our understanding has improved regarding the cascades of events that follow the initial binding of agonist to plasma membrane receptors and that lead to the cross-bridge movements that determine contraction. This advance in our knowledge was stimulated by use of single-and whole-cell channel recordings of plasma membrane currents and by description of the l3-receptor-GTP-binding protein-adenylate cyclase-cAMP coupling system, which serves as a model for other coupling mechanisms. The discovery of the receptor-activated inositol phospholipid transduction system has greatly stimulated research and led to advances in our understanding of mechanisms involved in smooth muscle con traction. Major advances were also triggered by the development of indicators for measuring free cytosolic calcium concentration and starting the unraveling of 2 the events involved in Ca + -dependent activation of contractile proteins. Al though most of the studies that led to our current understanding of these areas were performed on nonairway smooth muscle, these studies usually add to our understanding of airway smooth muscle, and there is an enlarging body of data that have been obtained on airway smooth muscle.

Airway Remodeling
Airway Remodeling

Author: Peter Howarth

Publisher: CRC Press

Published: 2001

Total Pages: 328

ISBN-13: 9780429132582

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This landmark volume discusses the characteristics and impact of the remodeling process on airway function and clinical disease expression within the airway in asthma, covering pharmacological therapies and possible future targets relevant to regulating the remodeling process. Emphasizes the importance of treating underlying airway inflammation and the relevance of structural alterations to the airway wall, including glandular increases, enhanced collagen deposition within the submucosa, increased vasculature, smooth hypertrophy, and hyperplasias! Tracing the development and maintenance of bronchial hyperresponsiveness, decline in lung function, and loss of reversibility evident in chronic asthma, Airway Remodelingdescribes the contribution of inflammatory cells in the development of airway structural changes examines how pharmaceutical agents act and whether existing treatments modify or prevent remodeling in chronically inflamed asthmatic airways considers whether neural pathways initiate as well as contribute to the airway inflammatory cascade that leads to remodeling reviews the action of cytokines and growth factors on ASM signaling outlines novel approaches to regulating smooth muscle growth clarifies whether permanent ventilatory incapacity in asthma is caused by the uncoupling of the airway and the role of the lung parenchyma details high-resolution computerized tomography scan to measure the internal size of the airway at baseline, during challenge, or after bronchodilatation and more!Improving lung function and quality of life by reducing the need for emergency care, hospital admissions, and systemic steroid administration, Airway Remodeling is a superb reference for pulmonologists and respiratory system specialists; physiologists; pneumologists; allergists; pharmacologists; molecular, cellular, and lung biologists; and graduate and medical school students in these disciplines.

Modeling Aspects of Airway Smooth Muscle Dynamics
Modeling Aspects of Airway Smooth Muscle Dynamics

Author: Nichole Caisse

Publisher:

Published: 2008

Total Pages: 110

ISBN-13:

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Smooth muscle is made up of highly organized cells arranged in sheets lining the walls of hollow organs and vessels. They are mechanistically distinct from skeletal and cardiac muscle cells with respect to contractile processes. Despite using most of the same motor proteins as the striated skeletal and cardiac muscles, the organization of the non-striated smooth muscle contractile structure (sarcomeres) has not been resolved. I am interested in determining what alterations need to be made in both mechanistic and kinetic models describing skeletal and cardiac muscle contraction to make them accurately applicable to the unique properties associated with smooth muscle. Of particular interest is how the mechanics of airway smooth muscle, (ASM) play an integral role in the pathophysiology of the respiratory system. Once precise mechanics of airway smooth muscle are understood we will have the ability to model its function in a more accurate way. Establishing a robust model for smooth muscle function will provide the framework for predicting for example, functional defects that lead to disease. Also, mathematical models can be used to guide the development of improved treatments for respiratory diseases such as asthma. In this thesis I explore various ideas of how to implement properties of airway smooth muscle into models of skeletal and cardiac muscle. I utilize both the known mechanics and kinetics of airway smooth muscle contraction to suggest a way in which a model for cardiac muscle contraction could be adapted to model smooth muscle contraction. Finally I suggest ways in which this model may effectively assist in further understanding asthma.

The Airway Smooth Muscle Response to Strain and the Relationship with Airway Hyper-responsiveness
The Airway Smooth Muscle Response to Strain and the Relationship with Airway Hyper-responsiveness

Author: Thomas Kenneth Ansell

Publisher:

Published: 2014

Total Pages:

ISBN-13:

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[Truncated abstract] Airway hyper-responsiveness (AHR, i.e. excessive bronchoconstriction to an inhaled bronchial challenge) is believed to be a major contributor to airflow limitation, a primary characteristic of asthma. The cause(s) of AHR remain unclear but likely involve abnormalities in airway smooth muscle (ASM) and/or airway wall structure/function. More recently, the dynamic mechanical environment of the lung has been identified as an important regulator of airway responsiveness and may be susceptible to inflammatory disease processes, contributing to AHR. In normal healthy individuals, deep inspiration (DI) produces a transient reversal of bronchoconstriction (i.e. bronchodilation). The underlying mechanism by which DI produces bronchodilation is thought to involve stretch-induced relaxation of ASM, due to perturbed cross-bridge binding and/or de-polymerisation of the contractile apparatus. However, the bronchodilatory response to DI is attenuated or abolished in patients with asthma and this may contribute to the development of AHR. The general aim of this thesis is to better understand the ASM response to strain during breathing manoeuvres and the relationship with AHR.

Equine Respiratory Medicine and Surgery
Equine Respiratory Medicine and Surgery

Author: Bruce C. McGorum

Publisher: Saunders Limited

Published: 2007

Total Pages: 705

ISBN-13: 9780702027598

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This title is directed primarily towards health care professionals outside of the United States. Equine Respiratory Medicine and Surgery provides up-to-date, in-depth coverage of the diagnosis and management of respiratory disorders in the horse. It discusses respiratory physiology and examination techniques, as well as a review of the medical and surgical problems that may be encountered, organized anatomically and progressing in logical fashion from the upper airways, larynx and sinuses, through the lower airways, the lungs, and diaphragm. Common conditions covered include infections, allergy, trauma, cysts, and tumors. High quality artwork, including relevant radiographic and ultrasonographic images, CAT scans, MRI images, and color photographs aid understanding and diagnosis. A truly international perspective includes guidelines for different geographic areas and racing jurisdictions. Features in-depth coverage of the role of the veterinarian in the management of athletic horses with respiratory tract diseases.

Analysing Airway Dynamics Using 2D Iterated Maps and Systems of ODEs
Analysing Airway Dynamics Using 2D Iterated Maps and Systems of ODEs

Author: Mo Wu

Publisher:

Published: 2013

Total Pages: 117

ISBN-13:

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The airway, providing a means for respiration, is important to human health. An understanding of the behaviour of the airways and their major structural components, such as airway smooth muscle, may give important insights into human health and disease processes. As such, the dynamics of both the airways and airway smooth muscle have been popular areas of research. Airway and airway smooth muscle dynamics have previously been studied separately from one another. However, it is known that there are important connections between the behaviour of these two systems. In this work, an extension of an existing 1D iterated map for modelling airway dynamics to a 2D iterated map, which includes a non-constant force-length relationship for airway smooth muscle, is examined. Adding a force-length relationship and length adaptation to the original 1D map is shown to not affect the stability of stationary points or the period-two oscillatory dynamics in the region of interest. However, a period-three oscillation was discovered which was not seen in the 1D map, implying the oscillatory dynamics have been changed by adding the force-length relationship and length adaptation. The work has extended this 2D iterated map into a 2D system of ODEs and examined the behaviour of this new, continuous model, through analytical and numerical approaches. The continuous model has been found to lack the oscillatory behaviour associated with the discrete maps. This approach for producing the continuous model and the subsequent analysis is expected to have important implications in the future for coupling airway dynamics with full PDE-based airway smooth muscle dynamics. The behavioural similarities and differences between the 1D, 2D discrete and ODE models have been examined, showing that much of the behaviour of this family of models is highly similar, however, differences, particularly in respect to the appearance of oscillatory behaviour, have been shown to exist.

Asthma and COPD
Asthma and COPD

Author: Peter J. Barnes

Publisher: Elsevier

Published: 2009-03-19

Total Pages: 897

ISBN-13: 0080920608

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The Second Edition of Asthma and COPD: Basic Mechanisms and Clinical Management continues to provide a unique and authoritative comparison of asthma and COPD. Written and edited by the world's leading experts, it continues to be a comprehensive review of the most recent understanding of the basic mechanisms of both conditions, specifically comparing their etiology, pathogenesis, and treatments. * Each chapter considers Asthma and COPD in side-by-side contrast and comparison – not in isolation - in the context of mechanism, triggers, assessments, therapies, and clinical management * Presents the latest and most comprehensive understandings of the mechanisms of inflammation in both Asthma and COPD * Most extensive reference to primary literature on both Asthma and COPD in one source. * Easy-to-read summaries of the latest advances alongside clear illustrations

Smooth Muscle Spontaneous Activity
Smooth Muscle Spontaneous Activity

Author: Hikaru Hashitani

Publisher: Springer

Published: 2019-06-10

Total Pages: 427

ISBN-13: 9811358958

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This book presents the commonality and heterogeneity of the mechanisms underlying smooth muscle spontaneous activity in various smooth muscle organs and in addition discusses their malfunctions in disease and their potential as novel therapeutic targets. To facilitate understanding, the volume is divided into five parts and covers 16 organs: airways, gastrointestinal tract (phasic muscle, tonic muscle), renal pelvis, ureter, urinary bladder, urethra, corporal tissue, prostate, uterus, oviducts, seminal vesicle, artery, vein, microvasculature, and lymphatic vessels. This structure will help readers to comprehend the most up-to-date information on the similarities and differences in the contractile mechanisms driving various smooth muscles as well as their potential manipulations in particular visceral organ pathologies. The vast advancements in gene, electrical recording, and imaging technologies in this field are also discussed, with review of past achievements and consideration of likely future developments. This book will be of worldwide interest to clinicians, students, and researchers alike.

Disease Pathways
Disease Pathways

Author: Anastasia P. Nesterova

Publisher: Elsevier

Published: 2019-10-18

Total Pages: 732

ISBN-13: 0128170875

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Disease Pathways: An Atlas of Human Disease Signaling Pathways is designed to fill a void of illustrated reviews about the cellular mechanisms of human diseases. It covers 42 of the most common non-oncologic diseases and illustrates the connections between the molecular causes of the disease and its symptoms. This resource provides readers with detailed information about the disease molecular pathways, while keeping the presentation simple. Pathway models that aggregate the knowledge about protein–protein interactions have become indispensable tools in many areas of molecular biology, pharmacology, and medicine. In addition to disease pathways, the book includes a comprehensive overview of molecular signaling biology and application of pathway models in the analysis of big data for drug discovery and personalized medicine. This is a must-have reference for general biologists, biochemists, students, medical workers, and everyone interested in the cellular and molecular mechanisms of human disease. Over 145 full-color illustrations of the molecular and cellular cascades underlying the disease pathology. Disease pathways are based on computational models from Elsevier’s Disease Pathway Collection, published for the first time outside of Pathway Studio® commercial software. Each relationship on the pathway models is supported by references to scientific articles and can be examined at freely available online resources.