Effect of time-varying load on degree of bronchoconstriction in the dog

1998 ◽  
Vol 85 (4) ◽  
pp. 1464-1470 ◽  
Author(s):  
Norihiro Shinozuka ◽  
Jean-Pierre Lavoie ◽  
James G. Martin ◽  
Jason H. T. Bates
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Lung Volume ◽  
In Vitro Study ◽  
Smooth Muscle Contraction ◽  
Lung Mechanics ◽  
Muscle Shortening

It is well established that the degree of airway smooth muscle shortening produced by a given dose of bronchial agonist is greatly affected by lung volume. The airways are tethered by parenchymal attachments, the tension of which increases progressively with lung volume, thereby presenting a commensurately increasing hindrance to smooth muscle contraction. Earlier studies (P. F. Dillon, M. O. Aksoy, S. P. Driska, and R. A. Murphy. Science 211: 495–497, 1981) presented evidence that smooth muscle contraction initially involves rapidly cycling cross bridges, which then change to noncycling (latch) bridges. They also suggested that most of the muscle shortening occurs during the early rapid cross-bridge phase. This implies that smooth muscle subject to a given load early in contraction should shorten less than when it is subject to the same load later on. An in vitro study (W. Li and N. L. Stephens. Can. J. Physiol. Pharmacol. 72: 1458–1463, 1994) obtained support for this notion. To test this hypothesis in vivo, we measured the changes in lung impedance at 1 and 6 Hz produced in dogs by a bolus intravenous injection of methacholine when lung volume was increased for 10 s at different times after injection. We found that the changes in mechanics were greatly inhibited, whereas lung volume was elevated. However, when lung volume was returned to its initial level, the lung mechanics continued to change at a rate unaffected by the preceding volume change. We conclude that temporary mechanical inhibition of airway smooth muscle shortening in the normal dog in vivo merely delays an otherwise normal course of contraction.

Models to study airway smooth muscle contraction in vivo, ex vivo and in vitro: Implications in understanding asthma

2013 ◽  
Vol 26 (1) ◽  
pp. 24-36 ◽  
Author(s):  
David Wright ◽  
Pawan Sharma ◽  
Min-Hyung Ryu ◽  
Paul-Andre Rissé ◽  
Melanie Ngo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Ex Vivo ◽  
Smooth Muscle Contraction

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.

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.

Role of platelets in contraction of canine tracheal muscle elicited by PAF in vitro

1988 ◽  
Vol 65 (2) ◽  
pp. 914-920 ◽  
Author(s):  
K. J. Popovich ◽  
G. Sheldon ◽  
M. Mack ◽  
N. M. Munoz ◽  
P. Denberg ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Airway Smooth Muscle ◽  
Airway Epithelium ◽  
Platelet Activating Factor ◽  
Smooth Muscle Contraction ◽  
Tracheal Smooth Muscle ◽  
Serotonin Antagonist

To elucidate mechanisms of platelet-activating factor (PAF)-induced contraction, we studied the effect of PAF on 203 canine tracheal smooth muscle (TSM) strips from 45 dogs in vitro in the presence and absence of platelets. PAF (10(-11) to 10(-7) M) alone caused no contraction of TSM even in the presence of airway epithelium. In the presence of 2 x 10(5) platelets/microliter, PAF was an extremely potent contractile agonist (threshold 10(-11) M). This response was inhibited by the PAF antagonist, CV-3988 (10(-6) M), and reversed by the serotonin antagonist, methysergide (EC50 = 3.7 +/- 0.79 x 10(-9) M). Neither atropine nor chlorpheniramine (10(-9) to 10(-6) M) attenuated the response to PAF + platelets. In the presence of platelets, 10(-7) M PAF caused an increase in perfusate concentration of serotonin from 0.93 +/- 0.037 x 10(-8) to 1.7 +/- 0.046 x 10(-8) M (P less than 0.001). Tachyphylaxis, previously demonstrated to be irreversible, was shown to be a platelet-dependent phenomenon; contraction could be repeated in the same TSM after addition of fresh platelets. We demonstrate that PAF-induced contraction of canine TSM is caused by the release of cellular intermediates such as serotonin from platelets. We also demonstrate the site of PAF-induced tachyphylaxis in airway smooth muscle contraction.

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.

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.

scholarly journals Potentiating TMEM16A channel function has no effect on airway goblet cells or bronchial and pulmonary vascular smooth muscle function

2020 ◽  
Author(s):  
Henry Danahay ◽  
Roy Fox ◽  
Sarah Lilley ◽  
Holly Charlton ◽  
Kathryn Adley ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Contraction ◽  
Goblet Cell ◽  
Pulmonary Arteries ◽  
Smooth Muscle Contraction ◽  
Cell Numbers ◽  
Channel Function ◽  
Mucin Release

AbstractThe calcium-activated chloride channel TMEM16A enables chloride secretion across several transporting epithelia, including in the airway where it represents a therapeutic target for the treatment of cystic fibrosis. Additional roles for TMEM16A have also been proposed, including enhancing goblet cell exocytosis, increasing goblet cell numbers and stimulating smooth muscle contraction. The aim of the present study was to test whether the pharmacological regulation of TMEM16A channel function, both potentiation and inhibition, could affect any of these proposed biological roles.In vitro, a recently described potent and selective TMEM16A potentiator (ETX001) failed to stimulate mucin release from primary human bronchial epithelial (HBE) cells over a 24h exposure period using both biochemical and imaging endpoints. In addition, treatment of HBE cells with ETX001 or a potent and selective TMEM16A inhibitor (Ani9) for 4 days did not influence mucin release or goblet cell formation. In vivo, a TMEM16A potentiator was without effect on goblet cell emptying in an IL-13 driven goblet cell metaplasia model.Using freshly isolated human bronchi and pulmonary arteries, neither ETX001 or Ani9 had any effect on the contractile or relaxant responses of the tissues. In vivo, ETX001 also failed to influence either lung or cardiovascular function when delivered directly into the airways of telemetered rats.Together, these studies do not support a role for TMEM16A in the regulation of goblet cell numbers or mucin release, or on the regulation of airway or pulmonary artery smooth muscle contraction.

A theoretical study of the effect of airway smooth muscle orientation on bronchoconstriction

1990 ◽  
Vol 69 (3) ◽  
pp. 995-1001 ◽  
Author(s):  
J. H. Bates ◽  
J. G. Martin
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Theoretical Study ◽  
Muscle Tension ◽  
Airway Wall ◽  
Inhibitory Mechanisms ◽  
Muscle Shortening ◽  
Elastic Coefficients

If airway smooth muscle shortened in vivo to the extent that it does in vitro, then maximal bronchoconstriction would result in complete closure of virtually all airways. The fact that this does not happen indicates the existence of inhibitory mechanisms preventing maximal muscle shortening. There are many factors potentially limiting shortening in vivo. In this study we investigated one of these factors, the orientation of the smooth muscle around the airway wall. The airway was modeled as a cylinder of given wall thickness around which the muscle was wound as a spiral. The longitudinal and circumferential elasticities of the airway were embodied in a 2 x 2 matrix of elastic coefficients. We investigated smooth muscle shortening under three conditions: 1) a longitudinally stiff airway, 2) a circumferentially stiff airway, and 3) a longitudinally and circumferentially compressible airway. In case 1, for a given degree of smooth muscle shortening, airway resistance increased markedly with increasing pitch of the smooth muscle spiral. On the other hand, the muscle tension required to elicit a given change in resistance also increased markedly with pitch. In case 2, the effect with increasing pitch was reversed. In case 3, resistance first increased and then decreased as spiral pitch increased. Similarly, the muscle tension required to elicit a given change in resistance first increased and then decreased with pitch. These results suggest that the orientation of the smooth muscle about the airway may be very important in determining airway responsiveness.

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