Airway diameter at different transpulmonary pressures in ex vivo sheep lungs: implications for deep inspiration-induced bronchodilation and bronchoprotection

Dong, Shoujin; Wang, Lu; Chitano, Pasquale; Paré, Peter D.; Seow, Chun Y.

doi:10.1152/ajplung.00208.2021

Cited by 6 publications

(10 citation statements)

References 54 publications

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“…Within each treated or untreated groups, the initial modulus (Fig. 4 A) was significantly greater axially compared to circumferentially for all tested regions, which aligns with sheep airway distension during deep inspiration [ 64 ]. The initial modulus decreased significantly with collagenase treatment for all regions and directions.…”

Section: Resultsmentioning

confidence: 81%

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Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

et al. 2023

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Background Common respiratory illnesses, such as emphysema and chronic obstructive pulmonary disease, are characterized by connective tissue damage and remodeling. Two major fibers govern the mechanics of airway tissue: elastin enables stretch and permits airway recoil, while collagen prevents overextension with stiffer properties. Collagenase and elastase degradation treatments are common avenues for contrasting the role of collagen and elastin in healthy and diseased states; while previous lung studies of collagen and elastin have analyzed parenchymal strips in animal and human specimens, none have focused on the airways to date. Methods Specimens were extracted from the proximal and distal airways, namely the trachea, large bronchi, and small bronchi to facilitate evaluations of material heterogeneity, and subjected to biaxial planar loading in the circumferential and axial directions to assess airway anisotropy. Next, samples were subjected to collagenase and elastase enzymatic treatment and tensile tests were repeated. Airway tissue mechanical properties pre- and post-treatment were comprehensively characterized via measures of initial and ultimate moduli, strain transitions, maximum stress, hysteresis, energy loss, and viscoelasticity to gain insights regarding the specialized role of individual connective tissue fibers and network interactions. Results Enzymatic treatment demonstrated an increase in airway tissue compliance throughout loading and resulted in at least a 50% decrease in maximum stress overall. Strain transition values led to significant anisotropic manifestation post-treatment, where circumferential tissues transitioned at higher strains compared to axial counterparts. Hysteresis values and energy loss decreased after enzymatic treatment, where hysteresis reduced by almost half of the untreated value. Anisotropic ratios exhibited axially led stiffness at low strains which transitioned to circumferentially led stiffness when subjected to higher strains. Viscoelastic stress relaxation was found to be greater in the circumferential direction for bronchial airway regions compared to axial counterparts. Conclusion Targeted fiber treatment resulted in mechanical alterations across the loading range and interactions between elastin and collagen connective tissue networks was observed. Providing novel mechanical characterization of elastase and collagenase treated airways aids our understanding of individual and interconnected fiber roles, ultimately helping to establish a foundation for constructing constitutive models to represent various states and progressions of pulmonary disease.

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Section: Resultsmentioning

confidence: 81%

“…Similarly, our study utilized samples from the main bronchus up to our defined small airway diameters. Due to the increased branching in smaller bronchi, we were unable to explore further distal airway regions which are conventionally termed small depending on the animal (< 4 mm diameter) [ 64 ].…”

Section: Discussionmentioning

confidence: 99%

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

et al. 2023

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“…However, because the lung is neither homogeneous nor isotropic, it is necessary to directly measure airway diameter in intact lungs. To address this matter directly, Dong et al [ 24 ] employed computed tomography (CT) to measure airway diameters and lung volumes at different transpulmonary pressures. Their findings revealed a significant increase in airway diameter and lung volume as the transpulmonary pressure increased from 5 to 30 cmH 2 O, with small airways exhibiting a much greater increase in diameter compared to large airways (Fig.…”

Section: How Much Are Intralobular Airways Distended During a Di?mentioning

confidence: 99%

“…The airways are grouped into 3 sizes in terms of their diameters, small (< 3 mm), medium (between 3–4 mm), and large (> 4 mm). Reproduced from Dong et al [ 24 ] with permission …”

Section: How Much Are Intralobular Airways Distended During a Di?mentioning

confidence: 99%

“…However, before accepting this hypothesis, it is crucial to determine whether the amount of stretch applied to ASM during a DI is significant enough to impact the muscle's contractility. Dong et al addressed this issue by first quantifying the amount of strain on the airways during a DI and then applying the same level of strain to isolated bronchial rings to evaluate its effect on ASM contractility in an ovine model [ 24 ]. As shown in Fig.…”

Section: Can the Amount Of Stretch In Asm Seen During A DI Reduce Asm...mentioning

confidence: 99%

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Critical roles of airway smooth muscle in mediating deep-inspiration-induced bronchodilation: a big stretch?

Yasuda,

Wang,

Chitano

et al. 2023

Respir Res

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Background Deep inspiration (DI) has been shown to induce bronchodilation and bronchoprotection in bronchochallenged healthy subjects, but not in asthmatics. Strain-induced relaxation of airway smooth muscle (ASM) is considered one of the factors responsible for these effects. Other factors include the release or redistribution of pulmonary surfactant, alteration in mucus plugs, and changes in airway heterogeneity. Main body The present review is focused on the DI effect on ASM function, based on recent findings from ex vivo sheep lung experiments showing a large change in airway diameter during a DI. The amount of stretch on the airways, when applied to isolated airway rings in vitro, caused a substantial decrease in ASM contractility that takes many minutes to recover. When challenged with a bronchoconstrictor, the increase in pulmonary resistance in the ex vivo ovine lungs is mostly due to the increase in airway resistance. Conclusions Although non-ASM related factors cannot be excluded, the large strain on the airways associated with a DI substantially reduces ASM contractility and thus can account for most of the bronchodilatory and bronchoprotective effects of DI.

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Airway and parenchymal tissue resistance and elastance in ex vivo sheep lungs: effects of bronchochallenge and deep inspiration

Dong

Wang

Chitano

et al. 2022

American Journal of Physiology-Lung Cellular and Molecular Phys

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Lung resistance (RL) is determined by airway and parenchymal tissue resistance, as well as the degree of heterogeneity in airway constriction. Deep inspirations (DIs) are known to reverse experimentally induced increase in RL, but the mechanism is not entirely clear. The first step towards understanding the effect of DI is to determine how each of the resistance components is affected by DI. In the present study, we measured RL and apparent airway resistance (RAW, which combines the effects of airway resistance and airway heterogeneity) simultaneously before and after a DI in acetylcholine (ACh)-challenged ex vivo sheep lungs. We found that at normal breathing frequency (0.25 Hz) ACh-challenge led to doubling of RL, 80.3% of that increase was caused by an increase in RAW; the increase in apparent tissue resistance (RT) was insignificant. 57.7% of the increase in RAW was abolished by a single DI. After subtracting RAW from RL, the remaining RT was mostly independent of ACh-challenge and its reduction after a DI came mostly from the change in the mechanical properties of lung parenchyma. We conclude that at normal breathing frequency, RL in an unchallenged lung is mostly composed of RT, and the increase in RL due to ACh-challenge stems mostly from the increase in RAW and that both RAW and RT can be greatly reduced by a DI, likely due to a reduction in true airway resistance and heterogeneity, as well as parenchymal tissue hysteresis post DI.

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Airway diameter at different transpulmonary pressures in ex vivo sheep lungs: implications for deep inspiration-induced bronchodilation and bronchoprotection

Cited by 6 publications

References 54 publications

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

Effects of tissue degradation by collagenase and elastase on the biaxial mechanics of porcine airways

Critical roles of airway smooth muscle in mediating deep-inspiration-induced bronchodilation: a big stretch?

Airway and parenchymal tissue resistance and elastance in ex vivo sheep lungs: effects of bronchochallenge and deep inspiration

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