Mechanical alterations of airway smooth muscle in a canine asthmatic model

Antonissen, L A; Mitchell, Robert W.; Kroeger, E A; Kepron, Wayne; Tse, Kam S.; Stephens, N. L.

doi:10.1152/jappl.1979.46.4.681

Cited by 132 publications

(72 citation statements)

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“…Fredberg has suggested, however, that an increased intrinsic rate of crossbridge cycling would make it more difficult for the force fluctuations to disrupt the reaction. This suggestion would be consistent with studies demonstrating increased intrinsic crossbridge cycling rates (shortening velocity) in allergen-sensitized muscle (16)(17)(18)(19). Thus asthmatic airway smooth muscle may have a greater actomyosin crossbridge cycling rate that may be intrinsic to the muscle and/or enhanced by the surrounding inflammatory environment.…”

Section: Discussionsupporting

confidence: 86%

“…Work from Newman Stephens laboratory has demonstrated increased expression of myosin light chain kinase (MLCK) in airway smooth muscle from individuals with asthma and a ragweed-sensitized dog model of airway hyperresponsiveness (16,17). Airway smooth muscle from these individuals with asthma and from sensitized dogs concomitantly demonstrated increased shortening velocity and capacity (17,18). Furthermore, seventh-generation human bronchi passively sensitized using human sera with high titers to house dust mite antigen showed, in addition to increased shortening velocity and capacity (19), robust myogenic responsiveness to quick stretch compared with sham-sensitized control airways (20).…”

Section: Mechanistic Explanations From In Vitro Studiesmentioning

confidence: 99%

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Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Mitchell¹,

Dowell²,

Solway³

et al. 2008

Proceedings of the American Thoracic Society

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Superimposition of force fluctuations on contracted tracheal smooth muscle (TSM) has been used to simulate normal breathing. Breathing has been shown to reverse lung resistance of individuals without asthma and animals given methacholine to contract their airways; computed tomography scans also demonstrated bronchial dilation after a deep inhalation in normal volunteers. This reversal of airway resistance and bronchial constriction are absent (or much diminished) in individuals with asthma. Many studies have demonstrated that superimposition of force oscillations on contracted airway smooth muscle results in substantial smooth muscle lengthening. Subsequent studies have shown that this force fluctuation-induced relengthening (FFIR) is a physiologically regulated phenomenon. We hypothesized that actin filament length in the smooth muscle of the airways regulates FFIR of contracted tissues. We based this hypothesis on the observations that bovine TSM strips contracted using acetylcholine (ACh) demonstrated amplitude-dependent FFIR that was sensitive to mitogen-activated protein kinase (p38 MAPK) inhibition-an upstream regulator of actin filament assembly. We demonstrated latrunculin B (sequesters actin monomers thus preventing their assimilation into filaments resulting in shorter filaments) greatly increases FFIR and jasplakinolide (an actin filament stabilizer) prevents the effects of latrunculin B incubation on strips of contracted canine TSM. We suspect that p38 MAPK inhibition and latrunculin B predispose to shorter actin filaments. These studies suggest that actin filament length may be a key determinant of airway smooth muscle relengthening and perhaps breathing-induced reversal of agonist-induced airway constriction. Keywords: actin filament length; latrunculin B; jasplakinolideMany studies have demonstrated that superimposition of force oscillations on contracted airway smooth muscle results in substantial smooth muscle lengthening in vitro (1-4), a phenomenon we refer to as force fluctuation-induced relengthening (FFIR). It has been proposed that imposition of these force oscillations simulate the effect of breathing on airway responsiveness and caliber. Shen and coworkers demonstrated in ventilated rabbits that breathing reduced methacholine-elicited airway resistance in a tidal volume-dependent manner (5). In normal individuals who demonstrated increased airway resistance to inhaled methacholine, the degree of bronchoconstriction could be reversed again by normal, tidal breathing (6, 7) or by taking a single deep inspiration (8-10). This airway dilation with deep inspiration also was demonstrated directly by looking at computed tomography (CT) scans of normal volunteers (8). Lung tethering forces on the conducting airways probably contributed to this dilation by loading the smooth muscle in the bronchiolar walls (8-10). However, this reversal of bronchoconstriction with breathing or deep inspiration is absent or minimal in individuals with asthma (9, 10); their airways remain constricted to methacholin...

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Section: Discussionsupporting

confidence: 86%

Section: Mechanistic Explanations From In Vitro Studiesmentioning

confidence: 99%

Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Mitchell¹,

Dowell²,

Solway³

et al. 2008

Proceedings of the American Thoracic Society

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“…The total maximum force observed by Brown et al and that of the present study were almost the same. PO and Vmax reported by Antonissen et al (1979) were 1211 g/cm2 and 0.23 l0/sec, respectively. The values of PO and Vmax obtained in the present study are 61% and 40%, respectively, of the values reported by Antonissen et al (1979).…”

Section: Vagal Stimulation Wasmentioning

confidence: 73%

“…PO and Vmax reported by Antonissen et al (1979) were 1211 g/cm2 and 0.23 l0/sec, respectively. The values of PO and Vmax obtained in the present study are 61% and 40%, respectively, of the values reported by Antonissen et al (1979). Muscle in vivo may differ quentitatively from that in vitro, probably due to not only differences in metabolism between in vivo blood perfused muscle and in vitro muscle bathed in physiological salt solution, but also due to differences between vagal and electrical field stimulation.…”

Section: Vagal Stimulation Wasmentioning

confidence: 73%

“…During dynamic respiratory maneuvers, the time course of airway caliber is determined by the balance of timing of passively length-cycled airway smooth muscle and shortening velocity of the contracted airway smooth muscle (Sasaki and Hoppin 1979). Stephens et al (1969) and Antonissen et al (1979) studied the shortening velocity of airway smooth muscle using excised trachealis muscle strips under electrical field stimulation and found that the force-velocity relationship was hyperbolic and could be described by Hill's equation (Hill 1938). They reported that the shortening velocity of the trachealis muscle was slower than that of the striated muscles and suggested that the trachealis muscle could not play a significant role in rapid adjustment of transmural forces transmitted to the airway by the considerably faster striated respiratory muscles.…”

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confidence: 99%

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Effect of duration of vagal stimulation on shortening velocity of in vivo canine trachealis muscle.

Okayama

Ishii

et al. 1989

Tohoku J. Exp. Med.

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We studied shortening velocity of in vivo canine trachealis muscle contracted by bilateral vagus nerve stimulation, as a function of duration of contraction. The cervical trachea was transected at two locations, cut at the ventral portion, and opened. One side of the cartilage cut was connected to a force transducer and the other to a lever with a given weight as an afterload, the length of which was measured by a linear displacement transducer. Bilateral vagosympathetic trunks were stimulated by supramaximal electrical impulses. With vagal stimulation, the trachealis muscle started to contract isometrically and at a given time the muscle was allowed to contract isotonically by unlocking a stopper at a given afterload. The shortening velocity was reduced with longer duration of active state. Ten sec after vagal stimulation the maximum force was 730+105 g/cm2 (mean ±s.D.) and maximum velocity at zero load calculated by Hill's equation was 0.092 to /sec. We conclude that the force-velocity relationship of in vivo canine trachealis muscle stimulated by vagus nerves exhibits a time-dependency similar to that in vitro. airway mechanics ; airway smooth muscle ; isotonic contraction ; vagal stimulation Constriction of airway smooth muscle controls total and local ventilation by changing airway resistances. During dynamic respiratory maneuvers, the time course of airway caliber is determined by the balance of timing of passively length-cycled airway smooth muscle and shortening velocity of the contracted airway smooth muscle (Sasaki and Hoppin 1979). Stephens et al. (1969) and Antonissen et al. (1979) studied the shortening velocity of airway smooth muscle using excised trachealis muscle strips under electrical field stimulation and found that the force-velocity relationship was hyperbolic and could be described by Hill's equation (Hill 1938). They reported that the shortening velocity of the

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Role of airway smooth muscle in asthma: Possible relation to the neuroendocrine system

Stephens¹,

He²,

Halayko

1993

Anat. Rec.

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Though not yet firmly established, it appears likely that the neuroendocrine system (NES) regulates airway smooth muscle function. As it is the latter which is altered in asthma, the importance of the role of the NES in this disease is clear. The fact that transmitters from the NE cells are released from their basal aspect, and are in close proximity to the subjacent airway smooth muscle, further indicates an interaction. The question then arises as to what are the experimental desiderata for conducting studies of the ASM. These should constitute what Sergei Sorokin has called the "Koch's postulates of airway smooth muscle research." As human tissues from asthmatics are difficult to obtain, animal models have been developed. The requirements are that, in these animals, the allergy be IgE based, that a congenital or familial factor be operative, that a noncholinergic nonadrenergic inhibitory system be a component of the neural regulatory system, and that the antigen for immunization be of a type commonly found in human asthmatics. Ideally, evidence of clinical asthma and exercise-induced asthma and nocturnal attacks should also be present. Unfortunately, no ideal animal models exist and one cannot talk about asthmatic animals, but only of animals with allergic bronchospasm. If in vitro research is to be conducted, there are additional requirements. The tissue should be from a relevant location. The tracheal smooth muscle which has been the favorite, purely because of its convenience, is not a good model. For the early asthmatic attack, central bronchi (3-5 mm diameter) should be used. Muscle strips obtained from them should be parallel-fibred and the cartilage plaques should be carefully dissected away, otherwise they contribute unwanted frictional forces when velocity is measured. Care should be taken to ensure that the epithelial cell layer is intact, as evidence indicates that it may regulate airway muscle function, though this has not been established for all the animal species used in asthma research. The isolated muscle strip should be in a steady state, particularly with respect to the functional variable under study, before definitive data are collected. Most importantly, it is shortening capacity that must be studied, as this is the in vitro analogue to in vivo narrowing of airways. Isometric force development provides information about wall stiffness and is of very little relevance to the elucidation of the mechanism of bronchospasm.(ABSTRACT TRUNCATED AT 400 WORDS)

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Mechanical alterations of airway smooth muscle in a canine asthmatic model

Cited by 132 publications

References 0 publications

Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Effect of duration of vagal stimulation on shortening velocity of in vivo canine trachealis muscle.

Role of airway smooth muscle in asthma: Possible relation to the neuroendocrine system

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