Nonlinear elasticity of the lung extracellular microenvironment is regulated by macroscale tissue strain

Jorba, Ignasi; Beltrán, Gabriel; Falcones, Bryan; Suki, Bélâ; Farré, Ramón; García-Aznar, J.M.; Navajas, Daniel

doi:10.1016/j.actbio.2019.05.023

Cited by 59 publications

(55 citation statements)

References 59 publications

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“…After 24 h of treatment, the increase of specific lung elastance suggested a stiffening of the ventilatable lung, possibly due to the increased rate of stress and strain application and/or impaired surfactant functioning. 19,20 High PEEP Groups. The application of high PEEP with two levels of mechanical power induced tremendous stress and strain.…”

Section: Discussionmentioning

confidence: 99%

Does Iso-mechanical Power Lead to Iso-lung Damage?

et al. 2020

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Background Excessive tidal volume, respiratory rate, and positive end-expiratory pressure (PEEP) are all potential causes of ventilator-induced lung injury, and all contribute to a single variable: the mechanical power. The authors aimed to determine whether high tidal volume or high respiratory rate or high PEEP at iso-mechanical power produce similar or different ventilator-induced lung injury. Methods Three ventilatory strategies—high tidal volume (twice baseline functional residual capacity), high respiratory rate (40 bpm), and high PEEP (25 cm H2O)—were each applied at two levels of mechanical power (15 and 30 J/min) for 48 h in six groups of seven healthy female piglets (weight: 24.2 ± 2.0 kg, mean ± SD). Results At iso-mechanical power, the high tidal volume groups immediately and sharply increased plateau, driving pressure, stress, and strain, which all further deteriorated with time. In high respiratory rate groups, they changed minimally at the beginning, but steadily increased during the 48 h. In contrast, after a sudden huge increase, they decreased with time in the high PEEP groups. End-experiment specific lung elastance was 6.5 ± 1.7 cm H2O in high tidal volume groups, 10.1 ± 3.9 cm H2O in high respiratory rate groups, and 4.5 ± 0.9 cm H2O in high PEEP groups. Functional residual capacity decreased and extravascular lung water increased similarly in these three categories. Lung weight, wet-to-dry ratio, and histologic scores were similar, regardless of ventilatory strategies and power levels. However, the alveolar edema score was higher in the low power groups. High PEEP had the greatest impact on hemodynamics, leading to increased need for fluids. Adverse events (early mortality and pneumothorax) also occurred more frequently in the high PEEP groups. Conclusions Different ventilatory strategies, delivered at iso-power, led to similar anatomical lung injury. The different systemic consequences of high PEEP underline that ventilator-induced lung injury must be evaluated in the context of the whole body. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

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Section: Discussionmentioning

confidence: 99%

Does Iso-mechanical Power Lead to Iso-lung Damage?

et al. 2020

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“…For example, Polio et al (2018), measured Y ae in porcine lung using cavitation rheology (6.1 ± 1.6 kPa), small amplitude oscillatory shear rheometry (3.3 ± 0.5), microindentation (1.4 ± 0.4), and uniaxial tension (3.4 ± 0.4) and showed that all these techniques provided values in the same range. Using AFM, Liu and Tschumperlin (2011) estimated a value around 5 kPa for mice, while Jorba et al (2019) obtained values around 10 kPa at low strain in rats. Cavalcante et al (2005) used their network model to estimate the effective alveolar wall stiffness to be ∼5 kPa.…”

Section: Discussionmentioning

confidence: 99%

“…Another important simplifying assumption in the analytical model is that the stress-strain behavior of the alveolar wall is linear with a constant elastic modulus. A recent study used atomic force microscopy (AFM) to measure alveolar septal wall stiffness in decellularized rat lung tissue and found that indentation stiffness increased from about 10 kPa at 0 strain to about 80 kPa at 0.3 strain (Jorba et al, 2019). While the mechanism underlying this non-linear behavior remains unclear, one possibility is that it reflects the progressive straightening of flaccid fibers (Sobin et al, 1988;Mercer and Crapo, 1990;Toshima et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

An Analytical Model for Estimating Alveolar Wall Elastic Moduli From Lung Tissue Uniaxial Stress-Strain Curves

et al. 2020

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The non-linear stress-strain behavior of uniaxially-stretched lung parenchyma is thought to be an emergent phenomenon arising from the ensemble behavior of its microscopic constituents. Such behavior includes the alignment and elongation of randomly oriented alveolar walls with initially flaccid fibers in the direction of strain. To account for the link between microscopic wall behavior and the macroscopic stress-strain curve, we developed an analytical model that represents both alignment and elongation of alveolar walls during uniaxial stretching. The model includes the kinetics and mechanical behavior of randomly oriented elastic alveolar walls that have a bending stiffness at their intersections. The alignment and stretch of the walls following incremental stretch of the tissue were determined based on energy minimization, and the total stress was obtained by differentiating the total energy density with respect to strain. The stress-strain curves predicted by the model were comparable to curves generated by a previously published numerical alveolar network model. The model was also fit to experimentally measured stress-strain curves in parenchymal strips obtained from mice with decreased lung collagen content, and from young and aged mice. This yielded estimates for the elastic modulus of an alveolar wall, which increased with age from 4.4 to 5.9 kPa (p = 0.043), and for the elastic modulus of fibers within the wall, which increased with age from 311 to 620 kPa (p = 0.001). This demonstrates the possibility of estimating alveolar wall mechanical properties in biological soft tissue from its macroscopic behavior given appropriate assumptions about tissue structure.

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“…As the venous return increases, the heart increases its force of contraction and resulting stroke volume. In contrast, the lungs possess a nonlinear elasticity owing to their extracellular microenvironment 46,47 . As the diaphragm contracts, a negative intrapleural pressure expands the lungs.…”

Section: Discussionmentioning

confidence: 99%

Cardiac and lung endothelial cells in response to fluid shear stress on physiological matrix stiffness and composition

et al. 2020

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Objective Preconditioning of endothelial cells from different vascular beds has potential value for re‐endothelialization and implantation of engineered tissues. Understanding how substrate stiffness and composition affects tissue‐specific cell response to shear stress will aid in successful endothelialization of engineered tissues. We developed a platform to test biomechanical and biochemical stimuli. Methods A novel polydimethylsiloxane‐based parallel plate flow chamber enabled application of laminar fluid shear stress of 2 dynes/cm2 for 12 hours to microvascular cardiac and lung endothelial cells cultured on cardiac and lung‐derived extracellular matrix. Optical imaging of cells was used to quantify cell changes in cell alignment. Analysis of integrin expression was performed using flow cytometry. Results Application of fluid shear stress caused the greatest cell alignment in cardiac endothelial cells seeded on polystyrene and lung endothelial cells on polydimethylsiloxane. This resulted in elongation of the lung endothelial cells. αv and β3 integrin expression decreased after application of shear stress in both cell types. Conclusion Substrate stiffness plays an important role in regulating tissue‐specific endothelial response to shear stress, which may be due to differences in their native microenvironments. Furthermore, cardiac and lung endothelial cell response to shear stress was significantly regulated by the type of coating used.

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Nonlinear elasticity of the lung extracellular microenvironment is regulated by macroscale tissue strain

Cited by 59 publications

References 59 publications

Does Iso-mechanical Power Lead to Iso-lung Damage?

Does Iso-mechanical Power Lead to Iso-lung Damage?

An Analytical Model for Estimating Alveolar Wall Elastic Moduli From Lung Tissue Uniaxial Stress-Strain Curves

Cardiac and lung endothelial cells in response to fluid shear stress on physiological matrix stiffness and composition

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