Parenchymal tethering, airway wall stiffness, and the dynamics of bronchoconstriction

2007 ◽  
Vol 102 (5) ◽  
pp. 1912-1920 ◽  
Author(s):  
Jason H. T. Bates ◽  
Anne-Marie Lauzon
Keyword(s):  
Airway Resistance ◽  
Lung Parenchyma ◽  
Airway Wall ◽  
Lung Inflation ◽  
Wall Stiffness ◽  
Quantitative Understanding ◽  
Dynamical Nature ◽  
Force Velocity ◽  
Time Courses

We do not yet have a good quantitative understanding of how the force-velocity properties of airway smooth muscle interact with the opposing loads of parenchymal tethering and airway wall stiffness to produce the dynamics of bronchoconstriction. We therefore developed a two-dimensional computational model of a dynamically narrowing airway embedded in uniformly elastic lung parenchyma and compared the predictions of the model to published measurements of airway resistance made in rats and rabbits during the development of bronchoconstriction following a bolus injection of methacholine. The model accurately reproduced the experimental time-courses of airway resistance as a function of both lung inflation pressure and tidal volume. The model also showed that the stiffness of the airway wall is similar in rats and rabbits, and significantly greater than that of the lung parenchyma. Our results indicate that the main features of the dynamical nature of bronchoconstriction in vivo can be understood in terms of the classic Hill force-velocity relationship operating against elastic loads provided by the surrounding lung parenchyma and an airway wall that is stiffer than the parenchyma.

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

2008 ◽  
Vol 104 (6) ◽  
pp. 1601-1610 ◽  
Author(s):  
Ana Cojocaru ◽  
Charles G. Irvin ◽  
Hans C. Haverkamp ◽  
Jason H. T. Bates
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Time Course ◽  
Airway Resistance ◽  
Allergic Inflammation ◽  
Model Fit ◽  
Airway Wall ◽  
Pulmonary Endothelium ◽  
Wall Stiffness

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.

scholarly journals Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo

1997 ◽  
Vol 83 (2) ◽  
pp. 366-370 ◽  
Author(s):  
Robert H. Brown ◽  
Wayne Mitzner ◽  
Elizabeth M. Wagner
Keyword(s):  
Dose Response ◽  
Lung Volume ◽  
Bronchial Artery ◽  
Wall Thickening ◽  
Airway Wall ◽  
Lung Inflation ◽  
Wall Area ◽  
Airway Edema ◽  
Airway Constriction

Brown, Robert H., Wayne Mitzner, and Elizabeth M. Wagner.Interaction between airway edema and lung inflation on responsiveness of individual airways in vivo. J. Appl. Physiol. 83(2): 366–370, 1997.—Inflammatory changes and airway wall thickening are suggested to cause increased airway responsiveness in patients with asthma. In five sheep, the dose-response relationships of individual airways were measured at different lung volumes to methacholine (MCh) before and after wall thickening caused by the inflammatory mediator bradykinin via the bronchial artery. At 4 cmH2O transpulmonary pressure (Ptp), 5 μg/ml MCh constricted the airways to a maximum of 18 ± 3%. At 30 cmH2O Ptp, MCh resulted in less constriction (to 31 ± 5%). Bradykinin increased airway wall area at 4 and 30 cmH2O Ptp (159 ± 6 and 152 ± 4%, respectively; P < 0.0001). At 4 cmH2O Ptp, bradykinin decreased airway luminal area (13 ± 2%; P< 0.01), and the dose-response curve was significantly lower ( P = 0.02). At 30 cmH2O, postbradykinin, the maximal airway narrowing was not significantly different (26 ± 5%; P = 0.76). Bradykinin produced substantial airway wall thickening and slight potentiation of the MCh-induced airway constriction at low lung volume. At high lung volume, bradykinin increased wall thickness but had no effect on the MCh-induced airway constriction. We conclude that inflammatory fluid leakage in the airways cannot be a primary cause of airway hyperresponsiveness.

scholarly journals In Vivo Computed Tomography as a Research Tool to Investigate Asthma and COPD: Where Do We Stand?

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Gaël Dournes ◽  
Michel Montaudon ◽  
Patrick Berger ◽  
François Laurent
Keyword(s):  
Computed Tomography ◽  
Quantitative Research ◽  
Three Dimensional ◽  
Lung Parenchyma ◽  
Airway Disease ◽  
Bronchial Tree ◽  
Research Tool ◽  
Airway Wall ◽  
Clinical Tool

Computed tomography (CT) is a clinical tool widely used to assess and followup asthma and chonic obstructive pulmonary disease (COPD) in humans. Strong efforts have been made the last decade to improve this technique as a quantitative research tool. Using semiautomatic softwares, quantification of airway wall thickness, lumen area, and bronchial wall density are available from large to intermediate conductive airways. Skeletonization of the bronchial tree can be built to assess its three-dimensional geometry. Lung parenchyma density can be analysed as a surrogate of small airway disease and emphysema. Since resident cells involve airway wall and lung parenchyma abnormalities, CT provides an accurate and reliable research tool to assess their role in vivo. This litterature review highlights the most recent advances made to assess asthma and COPD with CT, and also their drawbacks and the place of CT in clarifying the complex physiopathology of both diseases.

Effect of lung inflation in vivo on airways with smooth muscle tone or edema

1997 ◽  
Vol 82 (2) ◽  
pp. 491-499 ◽  
Author(s):  
Robert H. Brown ◽  
Wayne Mitzner ◽  
Yonca Bulut ◽  
Elizabeth M. Wagner
Keyword(s):  
Smooth Muscle ◽  
Total Lung Capacity ◽  
Muscle Tone ◽  
Transpulmonary Pressure ◽  
Airway Wall ◽  
Lung Inflation ◽  
Airway Narrowing ◽  
Lung Capacity ◽  
Luminal Area

Brown, Robert H., Wayne Mitzner, Yonca Bulut, and Elizabeth M. Wagner. Effect of lung inflation in vivo on airways with smooth muscle tone or edema. J. Appl. Physiol. 82(2): 491–499, 1997.—Fibrous attachments to the airway wall and a subpleural surrounding pressure can create an external load against which airway smooth muscle must contract. A decrease in this load has been proposed as a possible cause of increased airway narrowing in asthmatic individuals. To study the interaction between the airways and the surrounding lung parenchyma, we investigated the effect of lung inflation on relaxed airways, airways contracted with methacholine, and airways made edematous by infusion of bradykinin into the bronchial artery. Measurements were made in anesthetized sheep by using high-resolution computed tomography to visualize changes in individual airways. During methacholine infusion, airway area was decreased but increased minimally with increases in transpulmonary pressure. Bradykinin infusion caused a 50% increase in airway wall area and a small decrease in airway luminal area. In contrast to airways contracted with methacholine, the luminal area after bradykinin increased substantially with increases in transpulmonary pressure, reaching 99% of the relaxed area at total lung capacity. Thus airway edema by itself did not prevent full distension of the airway at lung volumes approaching total lung capacity. Therefore, we speculate that if a deep inspiration fails to relieve airway narrowing in vivo, this must be a manifestation of airway smooth muscle contraction and not airway wall edema.

Airway resistance and tissue elastance from input or transfer impedance in bronchoconstricted monkeys

2001 ◽  
Vol 90 (2) ◽  
pp. 571-578 ◽  
Author(s):  
Kristin R. Black ◽  
Bela Suki ◽  
Jeffrey B. Madwed ◽  
Andrew C. Jackson
Keyword(s):  
Airway Resistance ◽  
Nonhuman Primates ◽  
Lung Parenchyma ◽  
Airway Wall ◽  
Tissue Properties ◽  
Cynomolgus Monkeys ◽  
Airway Constriction ◽  
Tissue Resistance ◽  
System Input ◽  
Tissue Elastance

Ascaris suum (AS) challenge in nonhuman primates is used as an animal model of human asthma. The primary goal of this study was to determine whether the airways and respiratory tissues in monkeys that are bronchoconstricted by AS inhalation behave similarly to those in asthmatic humans. Airway resistance (Raw) and tissue elastance (Eti) were estimated from respiratory system input (Zin) or transfer (Ztr) impedance. Zin (0.4–20 Hz) and Ztr (2–128 Hz) were measured in anesthetized cynomolgus monkeys ( n = 10) under baseline (BL) and post-AS challenge conditions. Our results indicate that AS challenge in monkeys produces 1) predominately an increase in Raw and not tissue resistance, 2) airway wall shunting at higher AS doses, and 3) heterogeneous airway constriction resulting in a decrease of lung parenchyma effective compliance. We investigated whether the airway and tissue properties estimated from Zin and Ztr were similar and found that Raw estimated from Zin and Ztr were correlated [ r 2 = 0.76], not significantly different at BL (13.6 ± 1.4 and 13.1 ± 0.9 cmH2O · l−1 · s−1, respectively), but significantly different post-AS (20.5 ± 4.5 cmH2O · l−1 · s−1and 18.5 ± 5.2 cmH2O · l−1 · s−1). There was no correlation between Eti estimated from Zin and Ztr. The changes in lung mechanical properties in AS-bronchoconstricted monkeys are similar to those recently reported in human asthma, confirming that this is a reasonable model of human asthma.

Training-induced alterations of the in vivo force-velocity relationship of human muscle

1981 ◽  
Vol 51 (3) ◽  
pp. 750-754 ◽  
Author(s):  
V. J. Caiozzo ◽  
J. J. Perrine ◽  
V. R. Edgerton
Keyword(s):  
Training Group ◽  
Knee Extension ◽  
Knee Extensors ◽  
Velocity Relationship ◽  
Slow Velocity ◽  
Group A ◽  
Force Velocity ◽  
Group B ◽  
Relationship Of

Seventeen male and female subjects (ages 20–38 yr) were tested pre- and posttraining for maximal knee extension torque at seven specific velocities (0, 0.84, 1.68, 2.51, 3.35, 4.19, and 5.03 rad . s-1) with an isokinetic dynamometer. Maximal knee extension torques were recorded at a specific joint angle (0.52 rad below the horizontal plane) for all test speeds. Subjects were randomly assigned to one of three experimental groups: group A, control, n = 7; group B, training at 1.68 rad . s-1, n = 5; or group C, training at 4.19 rad . s-1, n = 5. Subjects trained the knee extensors by performing two sets of 10 single maximal voluntary efforts three times a week for 4 wk. Before training, each training group exhibited a leveling-off of muscular tension in the slow velocity-high force region of the in vivo force-velocity relationship. Training at 1.68 rad . s-1 resulted in significant (P less than 0.05) improvements at all velocities except for 5.03 rad . s-1 and markedly affected the leveling-off in the slow velocity-high force region. Training at 4.19 rad . s-1 did not affect the leveling-off phenomenon but brought about significant improvements (P less than 0.05) at velocities of 2.51, 3.35, and 4.19 rad . s-1. The changes seen in the leveling-off phenomenon suggest that training at 1.68 rad . s-1 might have brought about an enhancement of motoneuron activation.

Control of glycolysis in vertebrate skeletal muscle during exercise

1996 ◽  
Vol 270 (4) ◽  
pp. R821-R829 ◽  
Author(s):  
U. Krause ◽  
G. Wegener
Keyword(s):  
Gastrocnemius Muscle ◽  
Rana Temporaria ◽  
High Capacity ◽  
Repeated Exercise ◽  
Frog Rana Temporaria ◽  
Time Courses ◽  
Fructose 1,6 Bisphosphate ◽  
Assay Conditions

The gastrocnemius muscle of the frog (Rana temporaria) has a high capacity for anaerobic glycolysis from glycogen. Glycolytic metabolites and effectors of phosphofructokinase, particularly the hexose bisphosphates, were followed in muscle during exercise (swimming between 5 s and 5 min), recovery (rest for up to 2 h after 5 min of swimming), and repeated exercise (swimming for up to 60 s after 2 h of recovery). Glycogen phosphorylase and phosphofructokinase were swiftly activated with exercise. The hexose bisphosphates followed markedly different time courses. Fructose 1,6-bisphosphate was transiently increased in both exercise and repeated exercise. This appears to be an effect rather than a cause of phosphofructokinase activation. Glucose 1,6-biphosphate was accumulated only while phosphofructokinase was active and was unchanged at other times. Fructose 2,6-biphosphate showed a 10-fold transient increase on exercise in rested frogs, almost disappeared from the muscle during recovery, and did not change during repeated exercise. Fructose 2,6-biphosphate is a potent activator of phosphofructokinase in vitro under near physiological assay conditions, and it may serve this function also in vivo during exercise. Glucose 1,6-biphosphate could be an activator of phosphofructokinase in repeated exercise when fructose 2,6-biphosphate is not available.

Surfactant metabolism of newborn lamb lungs studied in vivo

1980 ◽  
Vol 49 (6) ◽  
pp. 1091-1098 ◽  
Author(s):  
A. Jobe ◽  
M. Ikegami ◽  
I. Sarton-Miller ◽  
L. Barajas
Keyword(s):  
Palmitic Acid ◽  
Intravenous Injection ◽  
Half Life ◽  
Lamellar Body ◽  
Lung Parenchyma ◽  
Newborn Lamb ◽  
Specific Activities ◽  
Life Values ◽  
Surfactant Metabolism

Surfactant, microsomal, and lamellar body fractions were isolated from the lungs of 5-day-old lambs 0.21-55 h after the intravenous injection of radiolabeled palmitic acid. The specific activities as cpm/mumol phospholipid phosphate of phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were measured. The palmitate-labeled phospholipids disappeared from the lung parenchyma with a half-life of approximately 50 h. The radiolabel disappeared from phosphatidylcholine, saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine of microsomal fractions with initial half-life values of 4.5, 4.6, 1.9, and 23.9 h, respectively. The labeled phospholipids rapidly appeared in the lamellar body fraction and accumulated in the surfactant of the lambs in a linear fashion for 35 h. The curves for the labeling of surfactant with radiolabeled saturated phosphatidylcholine, phosphatidylglycerol, and phosphatidylethanolamine were similar to the curve for phosphatidylcholine.

scholarly journals Cardiac and Skeletal Actin Substrates Uniquely Tune Cardiac Myosin Strain-Dependent Mechanics

2018 ◽  
Author(s):  
Yihua Wang ◽  
Katalin Ajtai ◽  
Thomas P. Burghardt
Keyword(s):  
Resistive Load ◽  
Step Size ◽  
Actin Isoforms ◽  
Cardiac Actin ◽  
N Terminus ◽  
Human Adults ◽  
Force Velocity ◽  
Strain Dependent

ABSTRACTNative cardiac ventricular myosin (βmys) translates actin under load by transducing ATP free energy into mechanical work on actin during muscle contraction. Unitary βmys translation of actin is the myosin step-size. In vitro and in vivo βmys regulates contractile force and velocity by remixing 3 different step-sizes with stepping frequencies autonomously adapted to workload. Cardiac and skeletal actin isoforms have a specific 1:4 stoichiometry in normal adult human ventriculum. Human adults with inheritable hypertrophic cardiomyopathy (HCM) up-regulate skeletal actin in ventriculum suggesting that increasing skeletal/cardiac actin stoichiometry also adapts myosin force-velocity to respond to the muscle’s inability to meet demand.Nanometer scale displacement of quantum dot (Qdot) labeled actin under resistive load when impelled by βmys measures single myosin force-velocity in vitro in the Qdot assay. Unitary displacement classification constraints introduced here better separates myosin based signal from background upgrading step-size spatial resolution to the sub-nanometer range. Single βmys force-velocity for skeletal vs cardiac actin substrates was compared using the Qdot assay.Two competing myosin strain-sensitive mechanisms regulate step-size choices dividing mechanical characteristics into low- and high-force regimes. The actin isoforms alter myosin strain-sensitive regulation such that onset of the high-force regime, where a short step-size is a large or major contributor, is offset to higher loads by a unique cardiac ELC N-terminus/cardiac-actin contact at Glu6/Ser358. It modifies βmys force-velocity by stabilizing the ELC N-terminus/cardiac-actin association. Uneven onset of the high-force regime for skeletal vs cardiac actin dynamically changes force-velocity characteristics as skeletal/cardiac actin fractional content increases in diseased muscle.

scholarly journals Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease

2020 ◽  
Author(s):  
Rod A. Rahimi ◽  
Keshav Nepal ◽  
Murat Cetinbas ◽  
Ruslan I. Sadreyev ◽  
Andrew D. Luster
Keyword(s):  
Allergic Asthma ◽  
Allergic Airway Inflammation ◽  
Lung Parenchyma ◽  
Airway Disease ◽  
Gene Signature ◽  
Allergic Airway Disease ◽  
Transcriptional Analysis ◽  
Th2 Cells ◽  
Redundant Functions

ABSTRACTMemory CD4+ T helper type 2 (Th2) cells are critical in driving allergic asthma pathogenesis, yet the mechanisms whereby tissue-resident memory Th2 cells (Th2 Trm) and circulating memory Th2 cells collaborate in vivo remain unclear. Here, using a house dust mite (HDM) model of allergic asthma and parabiosis, we demonstrate that Th2 Trm and circulating memory Th2 cells perform non-redundant functions in vivo. Upon HDM re-challenge, circulating memory Th2 cells trafficked into the lung parenchyma and ignited perivascular inflammation to promote eosinophil and CD4+ T cell recruitment. In contrast, Th2 Trm proliferated near airways and promoted mucus metaplasia, airway hyper-responsiveness, and airway eosinophil activation. Transcriptional analysis revealed that Th2 Trm and circulating memory Th2 cells share a core Th2 gene signature, but also exhibit distinct transcriptional profiles. Specifically, Th2 Trm express a tissue adaptation signature, including genes involved in regulating and interacting with extracellular matrix. Our findings demonstrate that Th2 Trm and circulating memory Th2 cells are functionally and transcriptionally distinct subsets with unique roles in promoting allergic airway disease.SUMMARYHow memory Th2 cell subsets orchestrate allergic airway inflammation remains unclear. Rahimi et al. use a murine model of allergic asthma and parabiosis to demonstrate that tissue-resident and circulating memory Th2 cells are functionally distinct subsets with unique roles in promoting allergic airway disease.

Sign in / Sign up

Export Citation Format

Share Document