ORCID Profile
0000-0003-1412-762X
Current Organisation
Murdoch University
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Publisher: Elsevier BV
Date: 2016
DOI: 10.1016/J.RESP.2015.09.006
Abstract: Length adaptation is a phenomenon observed in airway smooth muscle (ASM) wherein over time there is a shift in the length-tension curve. There is potential for length adaptation to play an important role in airway constriction and airway hyper-responsiveness in asthma. Recent results by Ansell et al., 2015 (JAP 2014 10.1152/japplphysiol.00724.2014) have cast doubt on this role by testing for length adaptation using an intact airway preparation, rather than strips of ASM. Using this technique they found no evidence for length adaptation in intact airways. Here we attempt to resolve this apparent discrepancy by constructing a minimal mathematical model of the intact airway, including ASM which follows the classic length-tension curve and undergoes length adaptation. This allows us to show that (1) no evidence of length adaptation should be expected in large, cartilaginous, intact airways (2) even in highly compliant peripheral airways, or at more compliant regions of the pressure-volume curve of large airways, the effect of length adaptation would be modest and at best marginally detectable in intact airways (3) the key parameters which control the appearance of length adaptation in intact airways are airway compliance and the relaxation timescale. The results of this mathematical simulation suggest that length adaptation observed at the level of the isolated ASM may not clearly manifest in the normal intact airway.
Publisher: American Physiological Society
Date: 15-08-2013
DOI: 10.1152/JAPPLPHYSIOL.01286.2012
Abstract: 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 (P tm ) 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-P tm 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.
Publisher: Wiley
Date: 09-2009
DOI: 10.1111/J.1440-1843.2009.01596.X
Abstract: In adults, respiratory movements, such as tidal and deep breaths, reduce airway smooth muscle force and cause bronchodilation. Evidence suggests that these beneficial effects of oscillatory strain do not occur in children, possibly because of reduced coupling of the airways to lung tissue or maturational differences in the intrinsic response of the airways to oscillatory strain. The bronchodilator effects of oscillatory strain were compared in isolated airway segments from immature (3-4 weeks and 8-10 weeks old) and mature (18-20 weeks old) pigs. The lumen of fluid-filled bronchi was volume-oscillated to simulate tidal breaths and 0.5x, 2x and 4x tidal volumes. Contractions to acetylcholine and electrical field stimulation were recorded from the lumen pressure and were compared under oscillating and static conditions. Airway stiffness was determined from the litude of the lumen pressure cycles and the volume of oscillation. Volume oscillation reduced contractions to acetylcholine and electrical field stimulation in an litude-dependent manner and the percentage reduction was the same for the different stimuli across all age groups. There was no difference in the relaxed dynamic stiffness of airways from the different age groups. 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.
Publisher: American Physiological Society
Date: 15-04-2014
Publisher: Wiley
Date: 23-09-2014
DOI: 10.1111/BPH.12781
Publisher: Wiley
Date: 20-05-2016
DOI: 10.1111/RESP.12800
Abstract: While chronic inflammation of the airway wall and the failure of deep inspiration (DI) to produce bronchodilation are both common to asthma, whether pro-inflammatory cytokines modulate the airway smooth muscle response to strain during DI is unknown. The primary aim of the study was to determine how an inflammatory environment (simulated by the use of pro-inflammatory cytokines) alters the bronchodilatory response to DI. We used whole porcine bronchial segments in vitro that were cultured in medium containing tumour necrosis factor and interleukin-1β for 2 days. A custom-built servo-controlled syringe pump and pressure transducer was used to measure airway narrowing and to simulate tidal breathing with intermittent DI manoeuvres. Culture with tumour necrosis factor and interleukin-1β increased airway narrowing to acetylcholine but did not affect the bronchodilatory response to DI. The failure of DI to produce bronchodilation in patients with asthma may not necessarily involve a direct effect of pro-inflammatory cytokines on airway tissue. A relationship between inflammation and airway hyper-responsiveness is supported, however, regulated by separate disease processes than those which attenuate or abolish the bronchodilatory response to DI in patients with asthma.
Publisher: European Respiratory Society (ERS)
Date: 04-2009
DOI: 10.1183/09031936.00116908
Abstract: Airway relaxation in response to isoprenaline, sodium nitroprusside (SNP) and electrical field stimulation (EFS) was compared under static and dynamic conditions. The capacity of relaxants to reduce airway stiffness and, thus, potentially contribute to bronchodilation was also investigated. Relaxation responses were recorded in fluid filled bronchial segments from pigs under static conditions and during volume oscillations simulating tidal and twice tidal manoeuvres. Bronchodilation was assessed from the reduction in carbachol-induced lumen pressure, at isovolume points in pressure cycles produced by volume oscillation, and stiffness was assessed from cycle litudes. Under static conditions, all three inhibitory stimuli produced partial relaxation of the carbachol-induced contraction. Volume oscillation alone also reduced the contraction in an litude-dependent manner. However, maximum relaxation was observed when isoprenaline or SNP were combined with volume oscillation, virtually abolishing contraction at the highest drug concentrations. The proportional effects of isoprenaline and EFS were not different under static or oscillating conditions, whereas relaxation to SNP was slightly greater in oscillating airways. All three inhibitory stimuli also strongly reduced carbachol-induced airway stiffening. The current authors conclude that bronchoconstriction is strongly suppressed by combining the inhibitory stimulation of airway smooth muscle with cyclical mechanical strains. The capacity of airway smooth muscle relaxants to also reduce stiffness may further contribute to bronchodilation.
Publisher: American Physiological Society
Date: 03-2015
DOI: 10.1152/JAPPLPHYSIOL.00724.2014
Abstract: In isolated airway smooth muscle (ASM) strips, an increase or decrease in ASM length away from its current optimum length causes an immediate reduction in force production followed by a gradual time-dependent recovery in force, a phenomenon termed length adaptation. In situ, length adaptation may be initiated by a change in transmural pressure (P tm ), which is a primary physiological determinant of ASM length. The present study sought to determine the effect of sustained changes in P tm and therefore, ASM perimeter, on airway function. We measured contractile responses in whole porcine bronchial segments in vitro before and after a sustained inflation from a baseline P tm of 5 cmH 2 O to 25 cmH 2 O, or deflation to −5 cmH 2 O, for ∼50 min in each case. In one group of airways, lumen narrowing and stiffening in response to electrical field stimulation (EFS) were assessed from volume and pressure signals using a servo-controlled syringe pump with pressure feedback. In a second group of airways, lumen narrowing and the perimeter of the ASM in situ were determined by anatomical optical coherence tomography. In a third group of airways, active tension was determined under isovolumic conditions. Both inflation and deflation reduced the contractile response to EFS. Sustained P tm change resulted in a further decrease in contractile response, which returned to baseline levels upon return to the baseline P tm . These findings reaffirm the importance of P tm in regulating airway narrowing. However, they do not support a role for ASM length adaptation in situ under physiological levels of ASM lengthening and shortening.
No related grants have been discovered for Thomas Ansell.