Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Mitchell, Richard W.; Dowell, Maria; Solway, Julian; Lakser, Oren

doi:10.1513/pats.200705-058vs

Cited by 13 publications

(9 citation statements)

References 34 publications

(77 reference statements)

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“…The effect of increasing tone on the strain and decline of force caused by simulated breathing maneuvers has never been systematically investigated. However, previous studies have shown that ASM preshortened with high concentrations of ACh relengthens when subjected to force oscillations simulating breathing maneuvers (7,16,17,20,25). This phenomenon was dubbed force fluctuation-induced relengthening (7,17,20).…”

mentioning

confidence: 99%

Decrease of airway smooth muscle contractility induced by simulated breathing maneuvers is not simply proportional to strain

Pascoe

Seow

Paré

et al. 2013

Journal of Applied Physiology

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The lung is a dynamic organ and the oscillating stress applied to the airway wall during breathing maneuvers can decrease airway smooth muscle (ASM) contractility. However, it is unclear whether it is the stress or the attendant strain that is responsible for the decline of ASM force associated with breathing maneuvers, and whether tone can prevent the decline of force by attenuating the strain. To investigate these questions, ovine tracheal strips were subjected to oscillating stress that simulates breathing maneuvers, and the resulting strain and decline of force were measured in the absence or presence of different levels of tone elicited by acetylcholine. In relaxed ASM, high stress simulating 20 cm H(2)O-transpulmonary pressure excursions strained ASM strips by 20.7% and decreased force by 17.1%. When stress oscillations were initiated during measurement of ACh concentration-response curves, tone almost abrogated strain at an ACh concentration of 10(-6) M (1.1%) but the decline of force was not affected (18.9%). When stress oscillations were initiated after ACh-induced contraction had reached its maximal force, strain was almost abrogated at an ACh concentration of 10(-6) M (0.9%) and the decline of force was attenuated (10.1%). However, even at the highest ACh concentration (10(-4) M), substantial decline of force (6.1%) was still observed despite very small strain (0.7%). As expected, the results indicate that tone attenuated the strain experienced by ASM during breathing maneuver simulations. More surprisingly, the reduction of strain induced by tone was not proportional to its effect on the decline of force induced by simulated breathing maneuvers.

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mentioning

confidence: 99%

Decrease of airway smooth muscle contractility induced by simulated breathing maneuvers is not simply proportional to strain

Pascoe

Seow

Paré

et al. 2013

Journal of Applied Physiology

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“…Since the force produced by ASM in response to a given contractile stimulus is attenuated following an acute stretch (40), the bronchodilating and bronchoprotective effect of DI seen in vivo may be due to a regulated intrinsic property of ASM. It has also been recognized that fluctuating strains applied to ASM cause a decline in force (10,12,13,20,31) as well as a relengthening of contracted ASM (21,24). In contrast, breathing at low lung volume was shown to increase airway responsiveness (8) and cessation of tidal breathing during breath holding caused a decrease in tracheal and central bronchi diameter (25).…”

Section: Discussionmentioning

confidence: 99%

Increase in passive stiffness at reduced airway smooth muscle length: potential impact on airway responsiveness

Bossé

Solomon

Chin

et al. 2010

American Journal of Physiology-Lung Cellular and Molecular Phys

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The amplitude of strain in airway smooth muscle (ASM) produced by oscillatory perturbations such as tidal breathing or deep inspiration (DI) influences the force loss in the muscle and is therefore a key determinant of the bronchoprotective and bronchodilatory effects of these breathing maneuvers. The stiffness of unstimulated ASM (passive stiffness) directly influences the amplitude of strain. The nature of the passive stiffness is, however, not clear. In this study, we measured the passive stiffness of ovine ASM at different muscle lengths (relative to in situ length, which was used as a reference length, L(ref)) and states of adaptation to gain insights into the origin of this muscle property. The results showed that the passive stiffness was relatively independent of muscle length, possessing a constant plateau value over a length range from 0.62 to 1.25 L(ref). Following a halving of ASM length, passive stiffness decreased substantially (by 71%) but redeveloped over time ( approximately 30 min) at the shorter length to reach 65% of the stiffness value at L(ref), provided that the muscle was stimulated to contract at least once over a approximately 30-min period. The redevelopment and maintenance of passive stiffness were dependent on the presence of Ca(2+) but unaffected by latrunculin B, an inhibitor of actin filament polymerization. The maintenance of passive stiffness was also not affected by blocking myosin cross-bridge cycling using a myosin light chain kinase inhibitor or by blocking the Rho-Rho kinase (RhoK) pathway using a RhoK inhibitor. Our results suggest that the passive stiffness of ASM is labile and capable of redevelopment following length reduction. Redevelopment and maintenance of passive stiffness following muscle shortening could contribute to airway hyperresponsiveness by attenuating the airway wall strain induced by tidal breathing and DI.

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“…The stress excursions, and the attendant strain, experienced by ASM in vivo are important to consider because they alter ASM mechanics considerably(reviewed in [27]). Simulation of breathing maneuvers on ex vivo preparations of ASM decrease ASM force when the muscle is held in isometric condition [28] and cause re-lengthening when ASM is subjected to an isotonic or auxotonic load [29,30]. This suggests that the changes of lung volume occurring in vivo due to breathing maneuvers may be protective against excessive airway responsiveness because it decreases ASM contractility.…”

Section: Transpulmonary Pressure Swings That Stress and Strainmentioning

confidence: 99%

Airway Hyperresponsiveness in Asthma: A Better Understanding Yet to Yield Clinical Benefit

Bossé¹,

Lee‐Gosselin²,

Boulet³

et al. 2013

J Allergy Ther

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Airway inflammation and hyperresponsiveness (AHR) are important features of asthma. Both inflammation and AHR are complex traits that can each originate from a plethora of factors, where every factor can be independent, interconnected and dispensable. This review examines the complexity of the indices that we use to assess airway responsiveness. These indices entail intricate information regarding the individual and the combined dynamic behavior of all the airways that constitute the tracheobronchial tree during the activation of airway smooth muscle (ASM). Because many factors other than ASM contractility can influence airway narrowing, the defects responsible for the manifestation of AHR are difficult to infer. New tests and technologies are being developed to decipher the meaning of the indices of airway responsiveness and have already leaped forward our understanding of AHR. This review also gives prominence to the concept of ASM plasticity.ASM mass and contractile capacity is not fixed over time. Several facets of inflammation can increase ASM force indirectly over a prolong period of time by causing tissue damage and repair, which ultimately leads of airway wall remodeling that embodies an enlargement of ASM mass. This could contribute to the fixed component of AHR. The gain of force due to inflammation can also be transient and conditional to the presence of inflammatory mediators that are capable of increasing the contractile capacity of ASM. This could contribute to the variable, and more readily modifiable, component of AHR. We are now aware that a multitude of muscle and non-muscle factors can contribute to AHR within an asthmatic individual, and that these factors are often times distinct between individuals. Consequently, the relative contribution of a single factor within a group of patients is usually very small. This is the reason why our ever-growing understanding of AHR in asthma does not quite yet avail patients.

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Force Fluctuation induced Relengthening of Acetylcholine-contracted Airway Smooth Muscle

Cited by 13 publications

References 34 publications

Decrease of airway smooth muscle contractility induced by simulated breathing maneuvers is not simply proportional to strain

Decrease of airway smooth muscle contractility induced by simulated breathing maneuvers is not simply proportional to strain

Increase in passive stiffness at reduced airway smooth muscle length: potential impact on airway responsiveness

Airway Hyperresponsiveness in Asthma: A Better Understanding Yet to Yield Clinical Benefit

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