Empirical model for dynamic force-length behavior of airway smooth muscle

2002 ◽  
Vol 92 (2) ◽  
pp. 455-460 ◽  
Author(s):  
Ron C. Anafi ◽  
Theodore A. Wilson
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Internal Variable ◽  
Dynamic Force ◽  
First Order ◽  
Elastic Load ◽  
Muscle Dynamics ◽  
Muscle Shortening ◽  
Trachealis Muscle ◽  
Surrounding Parenchyma

An empirical mathematical model that describes the relation between force and length for dynamic loading of maximally activated airway smooth muscle is described. The model consists of three first-order, ordinary differential equations: one for muscle shortening, one for lengthening, and a third that describes the evolution of an internal variable that depends on muscle history. The model fits data on the dynamic force-length behavior of maximally activated trachealis muscle for a range of amplitudes and rates of shortening and lengthening. The muscle model is incorporated into a model for an intact airway tethered to the surrounding parenchyma. As an example of its use, the model airway is subjected to the loading that occurs during a deep breath. After the breath, the rate of muscle shortening is determined by the interaction between muscle dynamics and the elastic load that is imposed by interdependence forces.

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.

Qualitative immunoblot analysis of PKC isoforms expressed in airway smooth muscle

1997 ◽  
Vol 272 (4) ◽  
pp. L603-L607 ◽  
Author(s):  
H. Togashi ◽  
C. A. Hirshman ◽  
C. W. Emala
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Airway Smooth Muscle ◽  
Intracellular Signaling ◽  
Immunoblot Analysis ◽  
Calcium Dependent ◽  
Kinase C ◽  
Pkc Isoforms ◽  
Dependent Activity ◽  
Trachealis Muscle

Protein kinase C (PKC) was originally identified as a single serine/ threonine protein kinase with calcium- and phospholipid-dependent activity, but more recently PKC has been found to consist of a family of multiple isoenzymes with different biochemical characteristics, substrates, and cofactor requirements. PKC is particularly important in regulating airway smooth muscle (ASM) tone. Although a previous investigation has demonstrated PKC-beta, -delta, -epsilon, -theta and -zeta in canine trachealis muscle, additional PKC isoforms have not been characterized in ASM. Therefore, immunoblot analysis using nine isotype-specific antibodies was used to further characterize the expression of PKC isoforms in porcine ASM. In addition to the previously described beta-, delta-, epsilon-, and zeta-isoforms in ASM, the calcium-dependent alpha-isoform, and the calcium- and diacylglycerol-independent isoforms iota/lambda and mu were identified. This study demonstrates multiple PKC isoforms in porcine ASM that can participate in intracellular signaling pathways in this tissue.

In vivo and in vitro correlation of trachealis muscle contraction in dogs

1992 ◽  
Vol 73 (4) ◽  
pp. 1486-1493 ◽  
Author(s):  
M. Okazawa ◽  
K. Ishida ◽  
J. Road ◽  
R. R. Schellenberg ◽  
P. D. Pare
Keyword(s):  
Isometric Force ◽  
Optimal Length ◽  
Linear Elastic ◽  
Elastic Load ◽  
Muscle Shortening ◽  
Anesthetized Dogs ◽  
Trachealis Muscle ◽  
Isotonic Shortening

Maximal trachealis muscle shortening in vivo was compared with that in vitro in seven anesthetized dogs. In addition, the effect of graded elastic loads on the muscle was evaluated in vitro. In vivo trachealis muscle shortening, as measured using sonomicrometry, revealed maximal active shortening to be 28.8 +/- 11.7% (SD) of initial length. Trachealis muscle preparations from the same animals were studied in vitro to evaluate isometric force generation, isotonic shortening, and the effect of applying linear elastic loads to the trachealis muscle during contraction from optimal length. Maximal isotonic shortening was 66.8 +/- 8.4% of optimal length in vitro. Increasing elastic loads decreased active shortening and velocity of shortening in vitro in a hyperbolic manner. The elastic load required to decrease in vitro shortening to the extent of the shortening observed in vivo was similar to the estimated load provided by the tracheal cartilage. We conclude that decreased active shortening in vivo is primarily due to the elastic afterload provided by cartilage.

Canine trachealis muscle shortening and cartilage mechanics

2004 ◽  
Vol 96 (3) ◽  
pp. 1063-1068 ◽  
Author(s):  
P. J. Robinson ◽  
R. R. Schellenberg ◽  
Y. Wakai ◽  
J. Road ◽  
P. D. Paré
Keyword(s):  
Tracheal Cartilage ◽  
Active Length ◽  
Cartilage Mechanics ◽  
Elastic Load ◽  
Muscle Shortening ◽  
Tension Testing ◽  
Trachealis Muscle

Canine trachealis muscle will shorten by 70% of resting length when maximally stimulated in vitro. In contrast, trachealis muscle will shorten by only 30–40% when stimulated in vivo. To examine the possibility that an elastic load applied by the tracheal cartilage contributes to the in vivo limitation of shortening, single pairs of sonomicrometry crystals were inserted into the trachealis muscle at the level of the fifth cartilage ring in five dogs. The segment containing the crystals was then excised and mounted on a tension-testing apparatus. Points on the active length-tension curve and the passive length-tension relation of the cartilage only were determined. The preload applied to the muscle before contraction varied from 10 to 40 g (mean 21 ± 4 g). The afterload applied by the cartilage during trachealis contraction ranged from 13 to 56 g (30 ± 6 g). The calculated elastic afterloads were substantial and appeared to be sufficient to explain the degree of shortening observed in four of the seven rings; in the remaining three rings, the limitation of shortening was greater than would be expected from the elastic load provided by the cartilage. Additional sources of loading and/or additional mechanisms may contribute to limited in situ shortening. In summary, tracheal cartilage applies a preload and an elastic afterload to the trachealis that are substantial and contribute to the limitation of trachealis muscle shortening in vivo.

scholarly journals Series-to-parallel transition in the filament lattice of airway smooth muscle

2000 ◽  
Vol 89 (3) ◽  
pp. 869-876 ◽  
Author(s):  
Chun Y. Seow ◽  
Victor R. Pratusevich ◽  
Lincoln E. Ford
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Muscle Length ◽  
Thick Filament ◽  
Cycling Rate ◽  
Cross Bridge ◽  
Parallel Change ◽  
Force Velocity ◽  
Cross Bridges ◽  
Trachealis Muscle

Force-velocity curves measured at different times during tetani of sheep trachealis muscle were analyzed to assess whether velocity slowing could be explained by thick-filament lengthening. Such lengthening increases force by placing more cross bridges in parallel on longer filaments and decreases velocity by reducing the number of filaments spanning muscle length. From 2 s after the onset of stimulation, when force had achieved 42% of it final value, to 28 s, when force had been at its tetanic plateau for ∼15 s, velocity decreases were exactly matched by force increases when force was adjusted for changes in activation, as assessed from the maximum power value in the force-velocity curves. A twofold change in velocity could be quantitatively explained by a series-to-parallel change in the filament lattice without any need to postulate a change in cross-bridge cycling rate.

Tissue elastance influences airway smooth muscle shortening: comparison of mechanical properties among different species

2002 ◽  
Vol 80 (9) ◽  
pp. 865-871 ◽  
Author(s):  
Anabelle M. Opazo Saez ◽  
R Robert Schellenberg ◽  
Mara S Ludwig ◽  
Richard A Meiss ◽  
Peter D Paré
Keyword(s):  
Mechanical Properties ◽  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Isometric Force ◽  
Published Data ◽  
Passive Tension ◽  
Active Force ◽  
Muscle Shortening ◽  
Human Airways ◽  
Tissue Elastance

We have observed striking differences in the mechanical properties of airway smooth muscle preparations among different species. In this study, we provide a novel analysis on the influence of tissue elastance on smooth muscle shortening using previously published data from our laboratory. We have found that isolated human airways exhibit substantial passive tension in contrast to airways from the dog and pig, which exhibit little passive tension (<5% of maximal active force versus ~60% for human bronchi). In the dog and pig, airway preparations shorten up to 70% from Lmax (the length at which maximal active force occurs), whereas human airways shorten by only ~12% from Lmax. Isolated airways from the rabbit exhibit relatively low passive tension (~22% Fmax) and shorten by 60% from Lmax. Morphologic evaluation of airway cross sections revealed that 25-35% of the airway wall is muscle in canine, porcine, and rabbit airways in contrast to ~9% in human airway preparations. We postulate that the large passive tension needed to stretch the muscle to Lmax reflects the high connective tissue content surrounding the smooth muscle, which limits shortening during smooth muscle contraction by imposing an elastic load, as well as by causing radial constraint.Key words: isometric force, isotonic shortening, elastance.

Airway smooth muscle responsiveness from dogs with airway hyperresponsiveness after O3 inhalation

1988 ◽  
Vol 65 (1) ◽  
pp. 57-64 ◽  
Author(s):  
G. L. Jones ◽  
P. M. O'Byrne ◽  
M. Pashley ◽  
R. Serio ◽  
J. Jury ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Potassium Chloride ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Electrical Field Stimulation ◽  
Field Stimulation ◽  
Electrical Field ◽  
Trachealis Muscle

Airway hyperresponsiveness occurs after inhalation of O3 in dogs. The purpose of this study was to examine the responsiveness of trachealis smooth muscle in vitro to electrical field stimulation, exogenous acetylcholine, and potassium chloride from dogs with airway hyperresponsiveness after inhaled O3 in vivo and to compare this with the responsiveness of trachealis muscle from control dogs. In addition, excitatory junction potentials were measured with the use of single and double sucrose gap techniques in both groups of dogs to determine whether inhaled O3 affects the release of acetylcholine from parasympathetic nerves in trachealis muscle. Airway hyperresponsiveness developed in all dogs after inhaled O3 (3 ppm for 30 min). The acetylcholine provocative concentration decreased from 4.11 mg/ml before O3 inhalation to 0.66 mg/ml after O3 (P less than 0.0001). The acetylcholine provocative concentration increased slightly after control inhalation of dry room air. Airway smooth muscle showed increased responses to both electrical field stimulation and exogenous acetylcholine but not to potassium chloride in preparations from dogs with airway hyperresponsiveness in vivo. The increased response to electrical field stimulation was not associated with a change in excitatory junctional potentials. These results suggest that a postjunctional alteration in trachealis muscle function occurs after inhaled O3 in dogs, which may account for airway hyperresponsiveness after O3 in vivo.

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.

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.

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