Airway smooth muscle orientation in intraparenchymal airways

1997 ◽  
Vol 82 (1) ◽  
pp. 70-77 ◽  
Author(s):  
M. Lei ◽  
H. Ghezzo ◽  
M. F. Chen ◽  
D. H. Eidelman
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Serial Sections ◽  
Airway Wall ◽  
Transverse Axis ◽  
Mean Values ◽  
Airway Narrowing ◽  
Human Specimen ◽  
The Mean ◽  
Airway Tree

Lei, M., H. Ghezzo, M. F. Chen, and D. H. Eidelman.Airway smooth muscle orientation in intraparenchymal airways. J. Appl. Physiol. 82(1): 70–77, 1997.—Airway smooth muscle (ASM) shortening is the central event leading to bronchoconstriction. The degree to which airway narrowing occurs as a consequence of shortening is a function of both the mechanical properties of the airway wall as well as the orientation of the muscle fibers. Although the latter is theoretically important, it has not been systematically measured to date. The purpose of this study was to determine the angle of orientation of ASM (θ) in normal lungs by using a morphometric approach. We analyzed the airway tree of the left lower lobes of four cats and one human. All material was fixed with 10% buffered Formalin at a pressure of 25 cmH2O for 48 h. The fixed material was dissected along the airway tree to permit isolation of generations 4–18 in the cats and generations 5–22 in the human specimen. Each airway generation was individually embedded in paraffin. Five-micrometer-thick serial sections were cut parallel to the airway long axis and stained with hematoxylin-phloxine-saffron. Each block yielded three to five sections containing ASM. To determine θ, we measured the orientation of ASM nuclei relative to the transverse axis of the airway by using a digitizing tablet and a light microscope (×250) equipped with a drawing tube attachment. Inspection of the sections revealed extensive ASM crisscrossing without a homogeneous orientation. The θ was clustered between −20° and 20° in all airway generations and did not vary much between generations in any of the cats or in the human specimen. When θ was expressed without regard to sign, the mean values were 13.2° in the cats and 13.1° in the human. This magnitude of obliquity is not likely to result in physiologically important changes in airway length during bronchoconstriction.

Bronchoprotective effect of simulated deep inspirations in tracheal smooth muscle

2014 ◽  
Vol 117 (12) ◽  
pp. 1502-1513 ◽  
Author(s):  
Christopher D. Pascoe ◽  
Graham M. Donovan ◽  
Ynuk Bossé ◽  
Chun Y. Seow ◽  
Peter D. Paré
Keyword(s):  
Smooth Muscle ◽  
Lung Function ◽  
Airway Smooth Muscle ◽  
Forced Expiratory Volume ◽  
Airway Responsiveness ◽  
Tracheal Smooth Muscle ◽  
Airway Wall ◽  
Methacholine Challenge ◽  
Airway Narrowing ◽  
The Third

Deep inspirations (DIs) taken before an inhaled challenge with a spasmogen limit airway responsiveness in nonasthmatic subjects. This phenomenon is called bronchoprotection and is severely impaired in asthmatic subjects. The ability of DIs to prevent a decrease in forced expiratory volume in 1 s (FEV1) was initially attributed to inhibition of airway narrowing. However, DIs taken before methacholine challenge limit airway responsiveness only when a test of lung function requiring a DI is used (FEV1). Therefore, it has been suggested that prior DIs enhance the compliance of the airways or airway smooth muscle (ASM). This would increase the strain the airway wall undergoes during the subsequent DI, which is part of the FEV1 maneuver. To investigate this phenomenon, we used ovine tracheal smooth muscle strips that were subjected to shortening elicited by acetylcholine with or without prior strain mimicking two DIs. The compliance of the shortened strip was then measured in response to a stress mimicking one DI. Our results show that the presence of “DIs” before acetylcholine-induced shortening resulted in 11% greater relengthening in response to the third DI, compared with the prior DIs. This effect, although small, is shown to be potentially important for the reopening of closed airways. The effect of prior DIs was abolished by the adaptation of ASM to either shorter or longer lengths or to a low baseline tone. These results suggest that DIs confer bronchoprotection because they increase the compliance of ASM, which, consequently, promotes greater strain from subsequent DI and fosters the reopening of closed airways.

Determinants of airway smooth muscle shortening in excised canine lobes

1995 ◽  
Vol 78 (2) ◽  
pp. 608-614 ◽  
Author(s):  
M. Okazawa ◽  
S. Vedal ◽  
L. Verburgt ◽  
R. K. Lambert ◽  
P. D. Pare
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Wall ◽  
High Concentration ◽  
Airway Narrowing ◽  
Wall Area ◽  
Muscle Shortening ◽  
Mechanical Factors ◽  
Airway Dimensions ◽  
Wall Geometry

There is marked heterogeneity of airway narrowing in intraparenchymal airways in response to bronchoconstricting stimuli. We hypothesized that this heterogeneity results from variations in the structure of the airway wall. Freshly excised dog lung lobes were inflated to transpulmonary pressures (PL) of between 5 and 15 cmH2O, and an aerosol containing a high concentration of carbachol was administered. The lobes were fixed and processed for light-microscopic examination and morphometric analysis of membranous airway dimensions. The relationships of smooth muscle shortening to PL and airway dimensions were analyzed using multiple linear regression. The results show that airway smooth muscle shortening was greater at lower PL and in airways with larger internal perimeter and a greater number of folds per internal perimeter and that it was less in airways with greater inner wall area. We conclude that the magnitude and variability of airway smooth muscle shortening and airway narrowing in response to maximal constricting stimuli are influenced by mechanical factors related to airway wall geometry.

Airway narrowing and response to simulated deep inspiration in bronchial segments from subjects with fixed airflow obstruction

2020 ◽  
Vol 128 (4) ◽  
pp. 757-767
Author(s):  
Alvenia Cairncross ◽  
Robyn L. Jones ◽  
John G. Elliot ◽  
Peter K. McFawn ◽  
Alan L. James ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Volume Fraction ◽  
Airflow Obstruction ◽  
Deep Inspiration ◽  
Airway Wall ◽  
Airway Narrowing ◽  
Fixed Airflow Obstruction

The volume fraction of extracellular matrix (ECM) within the layer of airway smooth muscle (ASM) is increased in subjects with fixed airflow obstruction. We postulated that changes in ECM within the ASM layer will impact force transmission during induced contraction and/or in response to externally applied stresses like a deep inspiration (DI). Subjects were patients undergoing lung resection surgery who were categorized as unobstructed ( n = 12) or “fixed” obstructed ( n = 6) on the basis of preoperative spirometry. The response to a DI, assessed by the ratio of isovolumic flows from maximal and partial inspirations (M/P), was also measured preoperatively. M/P was reduced in the obstructed group ( P = 0.02). Postoperatively, bronchial segments were obtained from resected tissue, and luminal narrowing to acetylcholine and bronchodilation to simulated DI were assessed in vitro. Airway wall dimensions and the volume fraction of ECM within the ASM were quantified. Maximal airway narrowing to acetylcholine ( P = 0.01) and the volume fraction of ECM within the ASM layer ( P = 0.02) were increased in the obstructed group, without a change in ASM thickness. Whereas bronchodilation to simulated DI in vitro was not different between obstructed and unobstructed groups, it was correlated with increased M/P (bronchodilation/less bronchoconstriction) in vivo ( P = 0.03). The volume fraction of ECM was inversely related to forced expiratory volume in 1 s FEV1 %predicted ( P = 0.04) and M/P ( P = 0.01). Results show that in subjects with fixed airflow obstruction the mechanical behavior of the airway wall is altered and there is a contemporaneous shift in the structural composition of the ASM layer. NEW & NOTEWORTHY Cartilaginous airways from subjects with fixed airflow obstruction have an increase in the volume fraction of extracellular matrix within the airway smooth muscle layer. These airways are also intrinsically more reactive to a contractile stimulus, which is expected to contribute to airway hyperresponsiveness in this population, often attributed to geometric mechanisms. In view of these results, we speculate on how changes in extracellular matrix may impact airway mechanics.

A model of the mechanics of airway narrowing

1990 ◽  
Vol 69 (3) ◽  
pp. 849-860 ◽  
Author(s):  
B. R. Wiggs ◽  
R. Moreno ◽  
J. C. Hogg ◽  
C. Hilliam ◽  
P. D. Pare
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Dose Response ◽  
Fluid Dynamic ◽  
Tracheobronchial Tree ◽  
Wall Thickening ◽  
Airway Wall ◽  
Pulmonary Resistance ◽  
Airway Narrowing ◽  
Muscle Shortening

To examine the interaction between airway smooth muscle shortening and airway wall thickening on changes in pulmonary resistance, we have developed a model of the tracheobronchial tree that allows simulation of the mechanisms involved in airway narrowing. The model is based on the symmetrical dichotomous branching tracheobronchial tree as described by Weibel and uses fluid dynamic equations proposed by Pedley et al. to calculate inspiratory resistance during quiet tidal breathing. To allow for changes in lung volume, we used the airway pressure-area curves developed by Lambert et al. The model is easily implemented with a spreadsheet and personal computer that allows calculation of total and regional pulmonary resistance. At each airway generation in the model, provision is made for airway wall thickness, the maximal airway smooth muscle shortening achievable, and an S-shaped dose-response relationship to describe smooth muscle shortening. To test the validity of the model, we compared pressure-flow curves generated with the model with measurements of pulmonary resistance while normal subjects breathed air and 20% O2-80% He at a variety of lung volumes. By simulating progressive airway smooth muscle shortening, realistic pulmonary resistance vs. dose-response curves were produced. We conclude that this model provides realistic estimates of pulmonary resistance and shows potential for examining the various mechanisms that could produce excessive airway narrowing in disease.

scholarly journals Reduction in airway hyperresponsiveness to methacholine by the application of RF energy in dogs

2004 ◽  
Vol 97 (5) ◽  
pp. 1946-1953 ◽  
Author(s):  
Christopher J. Danek ◽  
Charles M. Lombard ◽  
Donald L. Dungworth ◽  
P. Gerard Cox ◽  
John D. Miller ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Radio Frequency ◽  
Airway Smooth Muscle ◽  
Airway Responsiveness ◽  
Airway Wall ◽  
Smooth Muscle Contractility ◽  
Airway Narrowing ◽  
Radio Frequency Energy ◽  
Before And After ◽  
Percent Decrease

We delivered controlled radio frequency energy to the airways of anesthetized, ventilated dogs to examine the effect of this treatment on reducing airway narrowing caused by a known airway constrictor. The airways of 11 dogs were treated with a specially designed bronchial catheter in three of four lung regions. Treatments in each of the three treated lung regions were controlled to a different temperature (55, 65, and 75°C); the untreated lung region served as a control. We measured airway responsiveness to local methacholine chloride (MCh) challenge before and after treatment and examined posttreatment histology to 3 yr. Treatments controlled to 65°C as well as 75°C persistently and significantly reduced airway responsiveness to local MCh challenge ( P ≤ 0.022). Airway responsiveness (mean percent decrease in airway diameter after MCh challenge) averaged from 6 mo to 3 yr posttreatment was 79 ± 2.2% in control airways vs. 39 ± 2.6% ( P ≤ 0.001) for airways treated at 65°C, and 26 ± 2.7% ( P ≤ 0.001) for airways treated at 75°C. Treatment effects were confined to the airway wall and the immediate peribronchial region on histological examination. Airway responsiveness to local MCh challenge was inversely correlated to the extent of altered airway smooth muscle observed in histology ( r = −0.54, P < 0.001). We conclude that the temperature-controlled application of radio frequency energy to the airways can reduce airway responsiveness to MCh for at least 3 yr in dogs by reducing airway smooth muscle contractility.

Does the length dependency of airway smooth muscle force contribute to airway hyperresponsiveness?

2013 ◽  
Vol 115 (9) ◽  
pp. 1304-1315 ◽  
Author(s):  
Audrey Lee-Gosselin ◽  
Chris D. Pascoe ◽  
Christian Couture ◽  
Peter D. Paré ◽  
Ynuk Bossé
Keyword(s):  
Smooth Muscle ◽  
Computational Model ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Muscle Force ◽  
Morphological Data ◽  
Airway Wall ◽  
Airway Walls ◽  
Computational Analyses ◽  
Human Bronchi

Airway wall remodeling and lung hyperinflation are two typical features of asthma that may alter the contractility of airway smooth muscle (ASM) by affecting its operating length. The aims of this study were as follows: 1) to describe in detail the “length dependency of ASM force” in response to different spasmogens; and 2) to predict, based on morphological data and a computational model, the consequence of this length dependency of ASM force on airway responsiveness in asthmatic subjects who have both remodeled airway walls and hyperinflated lungs. Ovine tracheal ASM strips and human bronchial rings were isolated and stimulated to contract in response to increasing concentrations of spasmogens at three different lengths. Ovine tracheal strips were more sensitive and generated greater force at longer lengths in response to acetylcholine (ACh) and K+. Equipotent concentrations of ACh were approximately a log less for ASM stretched by 30% and approximately a log more for ASM shortened by 30%. Similar results were observed in human bronchi in response to methacholine. Morphometric and computational analyses predicted that the ASM of asthmatic subjects may be elongated by 6.6–10.4% (depending on airway generation) due to remodeling and/or hyperinflation, which could increase ACh-induced force by 1.8–117.8% (depending on ASM length and ACh concentration) and enhance the increased resistance to airflow by 0.4–4,432.8%. In conclusion, elongation of ASM imposed by airway wall remodeling and/or hyperinflation may allow ASM to operate at a longer length and to consequently generate more force and respond to lower concentration of spasmogens. This phenomenon could contribute to airway hyperresponsiveness.

scholarly journals In vitro, in silico and in vivo study challenges the impact of bronchial thermoplasty on acute airway smooth muscle mass loss

2018 ◽  
Vol 51 (5) ◽  
pp. 1701680 ◽  
Author(s):  
Igor L. Chernyavsky ◽  
Richard J. Russell ◽  
Ruth M. Saunders ◽  
Gavin E. Morris ◽  
Rachid Berair ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Asthma Control ◽  
Muscle Mass ◽  
Airway Smooth Muscle ◽  
In Silico ◽  
Heat Distribution ◽  
Airway Wall ◽  
Epithelial Integrity

Bronchial thermoplasty is a treatment for asthma. It is currently unclear whether its histopathological impact is sufficiently explained by the proportion of airway wall that is exposed to temperatures necessary to affect cell survival.Airway smooth muscle and bronchial epithelial cells were exposed to media (37–70°C) for 10 s to mimic thermoplasty. In silico we developed a mathematical model of airway heat distribution post-thermoplasty. In vivo we determined airway smooth muscle mass and epithelial integrity pre- and post-thermoplasty in 14 patients with severe asthma.In vitro airway smooth muscle and epithelial cell number decreased significantly following the addition of media heated to ≥65°C. In silico simulations showed a heterogeneous heat distribution that was amplified in larger airways, with <10% of the airway wall heated to >60°C in airways with an inner radius of ∼4 mm. In vivo at 6 weeks post-thermoplasty, there was an improvement in asthma control (measured via Asthma Control Questionnaire-6; mean difference 0.7, 95% CI 0.1–1.3; p=0.03), airway smooth muscle mass decreased (absolute median reduction 5%, interquartile range (IQR) 0–10; p=0.03) and epithelial integrity increased (14%, IQR 6–29; p=0.007). Neither of the latter two outcomes was related to improved asthma control.Integrated in vitro and in silico modelling suggest that the reduction in airway smooth muscle post-thermoplasty cannot be fully explained by acute heating, and nor did this reduction confer a greater improvement in asthma control.

scholarly journals Decreased airway narrowing and smooth muscle contraction in hyperresponsive pigs

2002 ◽  
Vol 93 (4) ◽  
pp. 1296-1300 ◽  
Author(s):  
Debra J. Turner ◽  
Peter B. Noble ◽  
Matthew P. Lucas ◽  
Howard W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Porcine Model ◽  
Smooth Muscle Contraction ◽  
Airway Wall ◽  
Muscle Contractility ◽  
Smooth Muscle Contractility ◽  
Airway Narrowing

Increased smooth muscle contractility or reduced smooth muscle mechanical loads could account for the excessive airway narrowing and hyperresponsiveness seen in asthma. These mechanisms were investigated by using an allergen-induced porcine model of airway hyperresponsiveness. Airway narrowing to electric field stimulation was measured in isolated bronchial segments, over a range of transmural pressures (0–20 cmH2O). Contractile responses to ACh were measured in bronchial segments and in isolated tracheal smooth muscle strips isolated from control and test (ovalbumin sensitized and challenged) pigs. Test airways narrowed less than controls ( P < 0.0001). Test pigs showed reduced contractility to ACh, both in isolated bronchi ( P < 0.01) and smooth muscle strips ( P < 0.01). Thus isolated airways from pigs exhibiting airway hyperresponsiveness in vivo are hyporesponsive in vitro. The decreased narrowing in bronchi from hyperresponsive pigs may be related to decreased smooth muscle contractility. These data suggest that mechanisms external to the airway wall may be important to the hyperresponsive nature of sensitized lungs.

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