Airway smooth muscle shortening in excised canine lung lobes

1993 ◽  
Vol 74 (4) ◽  
pp. 1613-1621 ◽  
Author(s):  
M. Okazawa ◽  
T. R. Bai ◽  
B. R. Wiggs ◽  
P. D. Pare
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Cross Sections ◽  
Muscle Length ◽  
Elastic Recoil ◽  
Pulmonary Resistance ◽  
Airway Narrowing ◽  
Arterial Perfusion ◽  
Muscle Shortening ◽  
Lung Lobes

To estimate the importance of lung parenchymal airway interdependence in attenuating airway narrowing, airway smooth muscle shortening in response to nebulized carbachol was measured in excised canine lung lobes and compared with the calculated load applied by lung elastic recoil. Pulmonary resistance of matched right and left upper lobes of five dogs was measured in a pressure-compensated volume plethysmograph by forced oscillation (6 Hz) before and after administration of an aerosol of carbachol (250 mg/ml) or saline. Matched lobes were studied at transpulmonary pressures (PL) of 5, 7, 10, 12, and 15 cmH2O. The lungs were then fixed at that PL by pulmonary arterial perfusion with formaldehyde, and cross sections of multiple airways from each lobe (n = 275) were examined by use of morphometric techniques to measure luminal area and smooth muscle length. By use of the saline lobe as a control, percentage of muscle shortening and decrease in airway lumen area caused by carbachol could be calculated. Passive and active smooth muscle stresses in each airway were calculated from PL and the calculated change in peribronchial pressure for a given change in airway diameter. The increase in pulmonary resistance and average smooth muscle shortening after administration of carbachol was greater in lobes held at lower PL. There was marked variation in narrowing between airways within a lobe: smooth muscle shortening ranged between 0 and 65% but averaged < 45% at all levels of PL.(ABSTRACT TRUNCATED AT 250 WORDS)

Limitation of airway smooth muscle shortening by cartilage stiffness and lung elastic recoil in rabbits

1993 ◽  
Vol 75 (2) ◽  
pp. 738-744 ◽  
Author(s):  
R. H. Moreno ◽  
C. Lisboa ◽  
J. C. Hogg ◽  
P. D. Pare
Keyword(s):  
Smooth Muscle ◽  
Effective Dose ◽  
Airway Smooth Muscle ◽  
Maximal Response ◽  
Positive End Expiratory Pressure ◽  
Elastic Recoil ◽  
Pulmonary Resistance ◽  
Muscle Shortening

Airway smooth muscle can contract to 20% of its starting length when stimulated maximally and allowed to contract isotonically in vitro. In vivo airway smooth muscle contraction of this degree would result in widespread airway closure. We hypothesized that elastic loads related to cartilage stiffness and lung parenchyma-airway interdependence limit in vivo airway smooth muscle shortening. We measured pulmonary resistance in anesthetized tracheostomized New Zealand White rabbits before and after intravenous treatment with papain in a concentration that produced generalized cartilage softening. Papain treatment caused a significant increase in pulmonary resistance that was completely reversed by application of 4 cmH2O positive end-expiratory pressure and that was partially reversed by vagotomy. Papain pretreatment also resulted in a substantial alteration in the pulmonary resistance-dose relationship to intravenously administered acetylcholine. In addition, maximal resistance after the highest concentration of acetylcholine was greater in papain-treated animals than in the control animals, but the position of the dose-response relationship was not shifted (i.e., there was no change in the effective dose causing 50% maximal response). Application of 4 cmH2O positive end-expiratory pressure in untreated animals resulted in a marked decrease in the bronchoconstriction produced by an effective dose of acetylcholine causing 50% of maximal response, whereas application of 4 cmH2O negative end-expiratory pressure resulted in a marked enhancement of the bronchoconstrictor response to the same intravenous dose of acetylcholine. We conclude that cartilage elasticity and lung recoil are important determinants of the ability of airway smooth muscle to shorten and produce airway narrowing in vivo.

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.

In vivo loads on airway smooth muscle: the role of noncontractile airway structures

1992 ◽  
Vol 70 (4) ◽  
pp. 602-606 ◽  
Author(s):  
Philip Robinson ◽  
Mitsushi Okazawa ◽  
Tony Bai ◽  
Peter Paré
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Activation ◽  
Muscle Length ◽  
Tracheal Cartilage ◽  
Elastic Load ◽  
Muscle Shortening ◽  
Trachealis Muscle

The degree of airway smooth muscle contraction and shortening that occurs in vivo is modified by many factors, including those that influence the degree of muscle activation, the resting muscle length, and the loads against which the muscle contracts. Canine trachealis muscle will shorten up to 70% of starting length from optimal length in vitro but will only shorten by around 30% in vivo. This limitation of shortening may be a result of the muscle shortening against an elastic load such as could be applied by tracheal cartilage. Limitation of airway smooth muscle shortening in smaller airways may be the result of contraction against an elastic load, such as could be applied by lung parenchymal recoil. Measurement of the elastic loads applied by the tracheal cartilage to the trachealis muscle and by lung parenchymal recoil to smooth muscle of smaller airways were performed in canine preparations. In both experiments the calculated elastic loads applied by the cartilage and the parenchymal recoil explained in part the limitation of maximal active shortening and airway narrowing observed. We conclude that the elastic loads provided by surrounding structures are important in determining the degree of airway smooth muscle shortening and the resultant airway narrowing.Key words: elastic loads, tracheal cartilage, airway smooth muscle shortening.

Relationship of airway narrowing, compliance, and cartilage in isolated bronchial segments

2002 ◽  
Vol 92 (3) ◽  
pp. 1119-1124 ◽  
Author(s):  
P. B. Noble ◽  
D. J. Turner ◽  
H. W. Mitchell
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Electrical Field Stimulation ◽  
Cross Sectional ◽  
Intact Control ◽  
Airway Narrowing ◽  
Lumen Narrowing ◽  
Morphometric Assessment ◽  
Relationship Of

Structural components of the airway wall may act to load airway smooth muscle and restrict airway narrowing. In this study, the effect of load on airway narrowing was investigated in pig isolated bronchial segments. In some bronchi, pieces of cartilage were removed by careful dissection. Airway narrowing was produced by maximum electrical field stimulation. An endoscope was used to record lumen narrowing. The compliance of the bronchial segments was determined from the cross-sectional area of the lumen and the transmural pressure. Airway narrowing and the velocity of airway narrowing were increased in cartilage-removed airways compared with intact control bronchi. Morphometric assessment of smooth muscle length showed greater muscle shortening to acetylcholine in cartilage-removed airways than in controls. Airway narrowing was positively correlated with airway compliance. Compliance and area of cartilage were negatively correlated. These results show that airway narrowing is increased in compliant airways and that cartilage significantly loads airway smooth muscle in whole bronchi.

scholarly journals Shortening of airway smooth muscle is modulated by prolonging the time without simulated deep inspirations in ovine tracheal strips

2019 ◽  
Vol 127 (6) ◽  
pp. 1528-1538 ◽  
Author(s):  
Morgan Gazzola ◽  
Fatemeh Khadangi ◽  
Marine Clisson ◽  
Jonathan Beaudoin ◽  
Marie-Annick Clavel ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
In Vitro Study ◽  
Time Interval ◽  
Tidal Breathing ◽  
Bronchodilator Effect ◽  
Airway Narrowing ◽  
Biochemical Processes ◽  
Muscle Shortening

The shortening of airway smooth muscle (ASM) is greatly affected by time. This is because stimuli affecting ASM shortening, such as bronchoactive molecules or the strain inflicted by breathing maneuvers, not only alter quick biochemical processes regulating contraction but also slower processes that allow ASM to adapt to an ever-changing length. Little attention has been given to the effect of time on ASM shortening. The present study investigates the effect of changing the time interval between simulated deep inspirations (DIs) on ASM shortening and its responsiveness to simulated DIs. Excised tracheal strips from sheep were mounted in organ baths and either activated with methacholine or relaxed with isoproterenol. They were then subjected to simulated DIs by imposing swings in distending stress, emulating a transmural pressure from 5 to 30 cmH2O. The simulated DIs were intercalated by 2, 5, 10, or 30 min. In between simulated DIs, the distending stress was either fixed or oscillating to simulate tidal breathing. The results show that although shortening was increased by prolonging the interval between simulated DIs, the bronchodilator effect of simulated DIs (i.e., the elongation of the strip post- vs. pre-DI) was not affected, and the rate of re-shortening post-simulated DIs was decreased. As the frequency with which DIs are taken increases upon bronchoconstriction, our results may be relevant to typical alterations observed in asthma, such as an increased rate of re-narrowing post-DI. NEW & NOTEWORTHY The frequency with which patients with asthma take deep inspirations (DIs) increases during bronchoconstriction. This in vitro study investigated the effect of changing the time interval between simulated DIs on airway smooth muscle shortening. The results demonstrated that decreasing the interval between simulated DIs not only decreases shortening, which may be protective against excessive airway narrowing, but also increases the rate of re-shortening post-simulated DIs, which may contribute to the increased rate of re-narrowing post-DI observed in asthma.

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.

scholarly journals Dynamic equilibration of airway smooth muscle contraction during physiological loading

2002 ◽  
Vol 92 (2) ◽  
pp. 771-779 ◽  
Author(s):  
Jeanne Latourelle ◽  
Ben Fabry ◽  
Jeffrey J. Fredberg
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Experimental Method ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Transpulmonary Pressure ◽  
Smooth Muscle Contraction ◽  
Control Force ◽  
Airway Narrowing

Airway smooth muscle contraction is the central event in acute airway narrowing in asthma. Most studies of isolated muscle have focused on statically equilibrated contractile states that arise from isometric or isotonic contractions. It has recently been established, however, that muscle length is determined by a dynamically equilibrated state of the muscle in which small tidal stretches associated with the ongoing action of breathing act to perturb the binding of myosin to actin. To further investigate this phenomenon, we describe in this report an experimental method for subjecting isolated muscle to a dynamic microenvironment designed to closely approximate that experienced in vivo. Unlike previous methods that used either time-varying length control, force control, or time-invariant auxotonic loads, this method uses transpulmonary pressure as the controlled variable, with both muscle force and muscle length free to adjust as they would in vivo. The method was implemented by using a servo-controlled lever arm to load activated airway smooth muscle strips with transpulmonary pressure fluctuations of increasing amplitude, simulating the action of breathing. The results are not consistent with classical ideas of airway narrowing, which rest on the assumption of a statically equilibrated contractile state; they are consistent, however, with the theory of perturbed equilibria of myosin binding. This experimental method will allow for quantitative experimental evaluation of factors that were previously outside of experimental control, including sensitivity of muscle length to changes of tidal volume, changes of lung volume, shape of the load characteristic, loss of parenchymal support and inflammatory thickening of airway wall compartments.

Fluoroaluminate- and GTP gamma S-induced stress, shortening, and myosin phosphorylation in airway smooth muscle

1993 ◽  
Vol 265 (1) ◽  
pp. L73-L79
Author(s):  
C. M. Hai ◽  
C. B. Ma
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Binding Proteins ◽  
Muscle Length ◽  
Active Stress ◽  
Myosin Phosphorylation ◽  
Gtp Binding Proteins ◽  
Gtp Binding ◽  
Muscle Shortening ◽  
Gamma S

GTP-binding proteins in bovine tracheal smooth muscle were activated by fluoroaluminate and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S), and the sensitivities of fluoroaluminate- and GTP gamma S-induced active stress and myosin phosphorylation to muscle shortening were compared. Relative to the value of myosin phosphorylation at L0, unloaded shortening induced a 63% decrease in fluoroaluminate-activated steady-state myosin phosphorylation, but had no significant effect on GTP gamma S-activated myosin phosphorylation. These results were consistent with the hypothesis that shortening-sensitive and shortening-insensitive signal-transduction pathways coexist in airway smooth muscle. However, unlike myosin phosphorylation, active stress induced by fluoroaluminate was actually less sensitive to shortening. The amount of shortening necessary to reduce active stress to half of that at Lo was 65% in fluoroaluminate-activated tissues, but was only 34% in GTP gamma S-activated tissues. The observation of different sensitivities of fluoroaluminate-activated myosin phosphorylation and active stress suggests that GTP-binding proteins modulate the dependence of active stress on muscle length in smooth muscle.

Smooth muscle molecular mechanics in airway hyperresponsiveness and asthmaThis paper is one of a selection of papers published in this Special Issue, entitled the Young Investigators' Forum.

2007 ◽  
Vol 85 (1) ◽  
pp. 133-140 ◽  
Author(s):  
Fulvio R. Gil ◽  
Anne-Marie Lauzon
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Airway Remodeling ◽  
Force Production ◽  
Muscle Length ◽  
Protective Role ◽  
Respiratory Disorder ◽  
Airway Narrowing ◽  
Muscle Plasticity

Asthma is a respiratory disorder characterized by airway inflammation and hyperresponsiveness associated with reversible airway obstruction. The relative contributions of airway hyperresponsiveness and inflammation are still debated, but ultimately, airway narrowing mediated by airway smooth muscle contraction is the final pathway to asthma. Considerable effort has been devoted towards identifying the factors that lead to the airway smooth muscle hypercontractility observed in asthma, and this will be the focus of this review. Airway remodeling has been observed in severe and fatal asthma. However, it is unclear whether remodeling plays a protective role or worsens airway responsiveness. Smooth muscle plasticity is a mechanism likely implicated in asthma, whereby contractile filament rearrangements lead to maximal force production, independent of muscle length. Increased smooth muscle rate of shortening via altered signaling pathways or altered contractile protein expression has been demonstrated in asthma and in numerous models of airway hyperresponsiveness. Increased rate of shortening is implicated in counteracting the relaxing effect of tidal breathing and deep inspirations, thereby creating a contracted airway smooth muscle steady-state. Further studies are therefore required to understand the numerous mechanisms leading to the airway hyperresponsiveness observed in asthma as well as their multiple interactions.

Methacholine-induced bronchoconstriction and airway smooth muscle in the guinea pig

1996 ◽  
Vol 80 (2) ◽  
pp. 437-444 ◽  
Author(s):  
A. Opazo Saez ◽  
T. Du ◽  
N. S. Wang ◽  
J. G. Martin
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Guinea Pigs ◽  
Pulmonary Resistance ◽  
Mechanically Ventilated ◽  
Airway Narrowing ◽  
Luminal Area ◽  
Lung Resistance ◽  
The Relationship

We examined the role of airway smooth muscle (ASM) as a determinant of the site and extent of methacholine (MCh)-induced airway narrowing in anesthetized and mechanically ventilated guinea pigs. The sites of airway narrowing and ASM were determined in animals (n = 4) bronchoconstricted to 75, 60, 40, or 15% of the maximal lung resistance (RL,max) induced by aerosolized MCh and compared with a saline-challenged animal. The median luminal area of each animal was significantly inversely correlated to the percentage of RL,max (r = -0.95; P < 0.01). However, there was no correlation between the degree of narrowing of any given airway and the quantity of ASM of any given airway. The relationship between the amount of ASM and responsiveness to MCh was studied in different animals (n = 13). The range of the concentration of MCh required to reach 50% of RL,max (EC50) varied by 254-fold, but the RL,max had only a 3.6-fold range. There was no correlation between RL,max and ASM. However, there was a correlation between the log EC50 and ASM (r = -0.541; P<0.05) in intraparenchymal cartilaginous airways. In conclusion, morphometric measurements of airway narrowing are correlated with pulmonary resistance. Variability in the quantity of ASM does not appear to be a determinant of the heterogeneity of airway narrowing or of maximal bronchoconstriction among normal guinea pigs. However, the sensitivity to MCh is associated with differences in the amount of ASM in intraparenchymal cartilaginous airways.

Sign in / Sign up

Export Citation Format

Share Document