Abstract:This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
“…Immediately following dissection, lungs were inflated via syringe to 0.5 ml to avoid airway collapse. Lungs were then prepared for ventilation and digital image correlation (DIC) data collection as detailed extensively previously 28 , 29 . Briefly, lungs were lightly airbrushed with white paint for contrast to the black randomized speckle pattern, which was applied via a fine-mist spray bottle, enabling continuous point displacement tracking for DIC 35 .…”
Section: Methodsmentioning
confidence: 99%
“…1X PBS was used to maintain tissue moisture during testing. Specimens were ventilated and DIC data was collected concurrently, facilitating simultaneous measures of global pressures and volumes and local deformations and strains caused by lung expansion 28 , 29 , 36 . Figure 1 The test configuration is shown.…”
Section: Methodsmentioning
confidence: 99%
“…The ventilation testing sequence began with a preload of 5 cmH 2 O to establish a common datum state and ensure comparable analyses 26 , 29 . The testing protocol included three inflation-deflation preconditioning cycles with a subsequent fourth cycle for analysis 37 .…”
Section: Methodsmentioning
confidence: 99%
“…Lung tissue leaks are notoriously unavoidable as testing progresses, resulting in four viable control and three fibrotic specimens 16 . In agreement with former quasi-static studies 11 , 38 , frequencies were chosen to eliminate complex flow effects, while still maintaining physiological relevance 39 , 40 , as established previously 26 , 29 . DIC data was collected and analyzed as detailed in previous works 28 , 29 , briefly summarized below.…”
Section: Methodsmentioning
confidence: 99%
“…Here we explore murine lung mechanics in fibrotic versus healthy specimens by assessing their local strain behaviors as influenced by continuous global pressure–volume measures for the first time. Our established custom-designed electromechanical ventilation system imposes global loads and collects bulk pressure–volume measurements 26 , 27 ; the system is coupled with digital image correlation (DIC) technology to measure local tissue strains in response to various applied ventilation volumes and rates 28 , 29 . Use of DIC allows the novel connection of global to local behaviors, facilitates continuous measurement of temporally changing (evolutionary) tissue strain values, and measures full-field deformations to accurately assess tissue strain heterogeneity 30 , 31 .…”
Tissue remodeling in pulmonary disease irreversibly alters lung functionality and impacts quality of life. Mechanical ventilation is amongst the few pulmonary interventions to aid respiration, but can be harmful or fatal, inducing excessive regional (i.e., local) lung strains. Previous studies have advanced understanding of diseased global-level lung response under ventilation, but do not adequately capture the critical local-level response. Here, we pair a custom-designed pressure–volume ventilator with new applications of digital image correlation, to directly assess regional strains in the fibrosis-induced ex-vivo mouse lung, analyzed via regions of interest. We discuss differences between diseased and healthy lung mechanics, such as distensibility, heterogeneity, anisotropy, alveolar recruitment, and rate dependencies. Notably, we compare local and global compliance between diseased and healthy states by assessing the evolution of pressure-strain and pressure–volume curves resulting from various ventilation volumes and rates. We find fibrotic lungs are less-distensible, with altered recruitment behaviors and regional strains, and exhibit disparate behaviors between local and global compliance. Moreover, these diseased characteristics show volume-dependence and rate trends. Ultimately, we demonstrate how fibrotic lungs may be particularly susceptible to damage when contrasted to the strain patterns of healthy counterparts, helping to advance understanding of how ventilator induced lung injury develops.
“…Immediately following dissection, lungs were inflated via syringe to 0.5 ml to avoid airway collapse. Lungs were then prepared for ventilation and digital image correlation (DIC) data collection as detailed extensively previously 28 , 29 . Briefly, lungs were lightly airbrushed with white paint for contrast to the black randomized speckle pattern, which was applied via a fine-mist spray bottle, enabling continuous point displacement tracking for DIC 35 .…”
Section: Methodsmentioning
confidence: 99%
“…1X PBS was used to maintain tissue moisture during testing. Specimens were ventilated and DIC data was collected concurrently, facilitating simultaneous measures of global pressures and volumes and local deformations and strains caused by lung expansion 28 , 29 , 36 . Figure 1 The test configuration is shown.…”
Section: Methodsmentioning
confidence: 99%
“…The ventilation testing sequence began with a preload of 5 cmH 2 O to establish a common datum state and ensure comparable analyses 26 , 29 . The testing protocol included three inflation-deflation preconditioning cycles with a subsequent fourth cycle for analysis 37 .…”
Section: Methodsmentioning
confidence: 99%
“…Lung tissue leaks are notoriously unavoidable as testing progresses, resulting in four viable control and three fibrotic specimens 16 . In agreement with former quasi-static studies 11 , 38 , frequencies were chosen to eliminate complex flow effects, while still maintaining physiological relevance 39 , 40 , as established previously 26 , 29 . DIC data was collected and analyzed as detailed in previous works 28 , 29 , briefly summarized below.…”
Section: Methodsmentioning
confidence: 99%
“…Here we explore murine lung mechanics in fibrotic versus healthy specimens by assessing their local strain behaviors as influenced by continuous global pressure–volume measures for the first time. Our established custom-designed electromechanical ventilation system imposes global loads and collects bulk pressure–volume measurements 26 , 27 ; the system is coupled with digital image correlation (DIC) technology to measure local tissue strains in response to various applied ventilation volumes and rates 28 , 29 . Use of DIC allows the novel connection of global to local behaviors, facilitates continuous measurement of temporally changing (evolutionary) tissue strain values, and measures full-field deformations to accurately assess tissue strain heterogeneity 30 , 31 .…”
Tissue remodeling in pulmonary disease irreversibly alters lung functionality and impacts quality of life. Mechanical ventilation is amongst the few pulmonary interventions to aid respiration, but can be harmful or fatal, inducing excessive regional (i.e., local) lung strains. Previous studies have advanced understanding of diseased global-level lung response under ventilation, but do not adequately capture the critical local-level response. Here, we pair a custom-designed pressure–volume ventilator with new applications of digital image correlation, to directly assess regional strains in the fibrosis-induced ex-vivo mouse lung, analyzed via regions of interest. We discuss differences between diseased and healthy lung mechanics, such as distensibility, heterogeneity, anisotropy, alveolar recruitment, and rate dependencies. Notably, we compare local and global compliance between diseased and healthy states by assessing the evolution of pressure-strain and pressure–volume curves resulting from various ventilation volumes and rates. We find fibrotic lungs are less-distensible, with altered recruitment behaviors and regional strains, and exhibit disparate behaviors between local and global compliance. Moreover, these diseased characteristics show volume-dependence and rate trends. Ultimately, we demonstrate how fibrotic lungs may be particularly susceptible to damage when contrasted to the strain patterns of healthy counterparts, helping to advance understanding of how ventilator induced lung injury develops.
We advanced a novel model to calculate viscoelastic lung compliance and airflow resistance in presence of mucus, accounting for the quasi‐linear viscoelastic stress–strain response of the parenchyma (alveoli) tissue. We adapted a continuum‐based numerical modeling approach for the lung, integrating the fluid mechanics of the airflow within individual generations of the bronchi and alveoli. The model accounts for elasticity of the deformable bronchioles, resistance to airflow due to the presence of mucus within the bronchioles, and subsequent mucus flow. Simulated quasi‐dynamic inhalation and expiration cycles were used to characterize the net compliance and resistance of the lung, considering the rheology of the mucus and viscoelastic properties of the parenchyma tissue. The structure and material properties of the lung were identified to have an important contribution to the lung compliance and airflow resistance. The secondary objective of this work was to assess whether a higher frequency and smaller volume of harmonic air flow rate compared to a normal ventilator breathing cycle enhanced mucus outflow. Results predict, lower mucus viscosity and higher excitation frequency of breathing are favorable for the flow of mucus up the bronchi tree, towards the trachea.
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