Effects of simulated tidal and deep breathing on immature airway contraction to acetylcholine and nerve stimulation

Ansell, Thomas K.; Noble, Peter B.; Mitchell, Howard; West, Adrian R.; Fernandes, Lynette; McFawn, Peter K.

doi:10.1111/j.1440-1843.2009.01596.x

Cited by 14 publications

(13 citation statements)

References 39 publications

(95 reference statements)

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“…We chose to instead assess the effects of hyperinflation on bronchodilation to a continuous oscillatory protocol equivalent to an amplitude of twice a normal tidal breath. Previous studies have shown that when volume oscillation is held fixed to that producing a Δ5 cm H 2 O P tm in the relaxed airway, modest bronchodilation is observed but which is greatly increased when amplitude is raised to twice tidal (i.e. Δ10 cm H 2 O P tm ) .…”

Section: Discussionmentioning

confidence: 99%

Hyperinflation of bronchi in vitro impairs bronchodilation to simulated breathing and increases sensitivity to contractile activation

2018

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Section: Discussionmentioning

confidence: 99%

Hyperinflation of bronchi in vitro impairs bronchodilation to simulated breathing and increases sensitivity to contractile activation

2018

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“…Several studies have shown that the magnitude of the bronchodilatory effect is strain-amplitude dependent (1,11,33,34,46,57). However, it remains unclear how much the ASM is strained within the airway wall in vivo and how much strain is necessary to result in significant and sustained bronchodilation.…”

Section: Discussionmentioning

confidence: 99%

Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

Harvey

Parameswaran

Lutchen

2013

Journal of Applied Physiology

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Harvey BC, Parameswaran H, Lutchen KR. Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?. J Appl Physiol 115: 436 -445, 2013. First published May 30, 2013 doi:10.1152/japplphysiol.00009.2013.-Fluctuating forces imposed on the airway smooth muscle due to breathing are believed to regulate hyperresponsiveness in vivo. However, recent animal and human isolated airway studies have shown that typical breathing-sized transmural pressure (Ptm) oscillations around a fixed mean are ineffective at mitigating airway constriction. To help understand this discrepancy, we hypothesized that Ptm oscillations capable of producing the same degree of bronchodilation as observed in airway smooth muscle strip studies requires imposition of strains larger than those expected to occur in vivo. First, we applied increasingly larger amplitude Ptm oscillations to a statically constricted airway from a Ptm simulating normal functional residual capacity of 5 cmH2O. Tidal-like oscillations (5-10 cmH2O) imposed 4.9 Ϯ 2.0% strain and resulted in 11.6 Ϯ 4.8% recovery, while Ptm oscillations simulating a deep inspiration at every breath (5-30 cmH2O) achieved 62.9 Ϯ 12.1% recovery. These same Ptm oscillations were then applied starting from a Ptm ϭ 1 cmH2O, resulting in approximately double the strain for each oscillation amplitude. When extreme strains were imposed, we observed full recovery. On combining the two data sets, we found a linear relationship between strain and resultant recovery. Finally, we compared the impact of Ptm oscillations before and after constriction to Ptm oscillations applied only after constriction and found that both loading conditions had a similar effect on narrowing. We conclude that, while sufficiently large strains applied to the airway wall are capable of producing substantial bronchodilation, the Ptm oscillations necessary to achieve those strains are not expected to occur in vivo.airway smooth muscle; intact airways; bronchodilation; bronchoprotection; asthma WHEN PERIODIC LENGTH OSCILLATIONS mimicking tidal breathing and deep inspirations (DIs) are applied to airway smooth muscle (ASM) during or after excitation, the increase in ASM force is less than would otherwise have occurred, if the excitatory stimulus were applied while the ASM was static (13,21,61). This observation led to the notion that periodic length fluctuations perturb the binding of myosin to actin (14,33,38,48), or cause remodeling of the contractile apparatus (19,30,50), thereby limiting the resultant tension that the ASM can generate. With regard to asthma, the isolated ASM studies motivated the conjecture that the mechanism behind the beneficial effect of DIs in preventing airway hyperresponsiveness (AHR) is intricately tied to stretching of the ASM during breathing (13,17,29,48). By extrapolation, these ASM strip level studies led to the hypothesis that, in asthmatic subjects, conditions such as wall remodeling or the presence of a milieu of inflammatory mediators could all...

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“…Airway segments were dissected from the main stem bronchus of the left or right lower lobe. All side branches were ligated with surgical silk, and a ϳ20-mm-long airway segment was cannulated at both ends, as previous described (3,4). The mode generation was 18 at the distal and 12 at the proximal end (where trachea ϭ 0), with an internal diameter of ϳ2 mm at the distal end and ϳ3 mm at the proximal end.…”

Section: Methodsmentioning

confidence: 99%

“…In vitro, length oscillation (i.e., stretch) in isolated ASM strips (11,12,37,39) and oscillation of lumen volume in intact airways (i.e., whole airway segments) (3,4) attenuates active force. Increasing amplitude of oscillation produces greater attenuation of active force in an amplitude-dependant manner (12,14,15).…”

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confidence: 99%

Bronchodilatory response to deep inspiration in bronchial segments: the effects of stress vs. strain

Ansell

McFawn

Mitchell

et al. 2013

Journal of Applied Physiology

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During deep inspirations (DI), a distending force is applied to airway smooth muscle (ASM; i.e., stress) and the muscle is lengthened (i.e., strain), which produces a transient reversal of bronchoconstriction (i.e., bronchodilation). The aim of the present study was to determine whether an increase in ASM stress or the accompanying increase in strain mediates the bronchodilatory response to DI. We used whole porcine bronchial segments in vitro and a servo-controlled syringe pump that applied fixed-transmural pressure (Ptm) or fixed-volume oscillations, simulating tidal breathing and DI. The relationship between ASM stress and strain during oscillation was altered by increasing doses of acetylcholine, which stiffened the airway wall, or by changing the rate of inflation during DI, which utilized the viscous properties of the intact airway. Bronchodilation to DI was positively correlated with ASM strain (range of r values from 0.81 to 0.95) and negatively correlated with stress (range of r values from -0.42 to -0.98). Fast fixed-Ptm DI produced greater bronchodilation than slow DI, despite less ASM strain. Fast fixed-volume DI produced greater bronchodilation than slow DI, despite identical ASM strain. We show that ASM strain, rather than stress, is the critical determinant of bronchodilation and, unexpectedly, that the rate of inflation during DI also impacts on bronchodilation, independent of the magnitudes of either stress or strain.

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Effects of simulated tidal and deep breathing on immature airway contraction to acetylcholine and nerve stimulation

Abstract: The intrinsic response of the airway wall to equivalent dynamic strain did not differ in airways from pigs of different ages. These findings suggest that mechanisms external to the airway wall may produce age-related differences in the response to lung inflation during development.

Cited by 14 publications

References 39 publications

Hyperinflation of bronchi in vitro impairs bronchodilation to simulated breathing and increases sensitivity to contractile activation

Hyperinflation of bronchi in vitro impairs bronchodilation to simulated breathing and increases sensitivity to contractile activation

Can tidal breathing with deep inspirations of intact airways create sustained bronchoprotection or bronchodilation?

Bronchodilatory response to deep inspiration in bronchial segments: the effects of stress vs. strain

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