Computational models of ventilator induced lung injury and surfactant dysfunction

Bates, Jason H. T.; Smith, Bradford J.; Allen, Gilman B.

doi:10.1016/j.ddmod.2014.02.005

Cited by 8 publications

(8 citation statements)

References 52 publications

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“…A number of theoretical and experimental studies have demonstrated that the increase in viscosity and surface tension of airway surface liquid likely results in VILI. Two main physical mechanisms for VILI are lung tissue overdistention caused by surface tension-induced alterations in interalveolar micromechanics and atelectrauma to the epithelial cells during repetitive airway reopening and closure [39–41]. The prediction from an adjoining two-alveoli model by Chen et al [42] shows that the pattern of alveolar expansion can appear heterogeneous or homogeneous, strongly depending on differences in air-liquid interface tension on alveolar segments.…”

Section: Importance Of Rheological Measurements Of Airway Surface Liquidmentioning

confidence: 99%

Determination of rheology and surface tension of airway surface liquid: a review of clinical relevance and measurement techniques

et al. 2019

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By airway surface liquid, we mean a thin fluid continuum consisting of the airway lining layer and the alveolar lining layer, which not only serves as a protective barrier against foreign particles but also contributes to maintaining normal respiratory mechanics. In recent years, measurements of the rheological properties of airway surface liquid have attracted considerable clinical attention due to new advances in microrheology instruments and methods. This article reviews the clinical relevance of measurements of airway surface liquid viscoelasticity and surface tension from four main aspects: maintaining the stability of the airways and alveoli, preventing ventilator-induced lung injury, optimizing surfactant replacement therapy for respiratory syndrome distress, and characterizing the barrier properties of airway mucus to improve drug and gene delivery. Primary measuring techniques and methods suitable for determining the viscoelasticity and surface tension of airway surface liquid are then introduced with respect to principles, advantages and limitations. Cone and plate viscometers and particle tracking microrheometers are the most commonly used instruments for measuring the bulk viscosity and microviscosity of airway surface liquid, respectively, and pendant drop methods are particularly suitable for the measurement of airway surface liquid surface tension in vitro. Currently, in vivo and in situ measurements of the viscoelasticity and surface tension of the airway surface liquid in humans still presents many challenges.

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Section: Importance Of Rheological Measurements Of Airway Surface Liquidmentioning

confidence: 99%

Determination of rheology and surface tension of airway surface liquid: a review of clinical relevance and measurement techniques

et al. 2019

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“…The greatest progress in the treatment of acute respiratory diseases has been mechanical ventilation. While use of mechanical ventilation has significant therapeutic benefits, improper use of this treatment (such as excessive usage time or incorrect parameter settings), may lead to or aggravate damage to the patient's lung tissue through various mechanisms, which is called ventilator-induced lung injury (VILI)1. To improve the therapeutic outcomes of patients who require mechanical ventilation, clarification of the mechanism of VILI and the development of new approaches for its prevention warrant further study.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen sulfide treatment alleviated ventilator-induced lung injury through regulation of autophagy and endoplasmic reticulum stress

Ge¹,

Sun²,

Fei³

et al. 2019

Int. J. Biol. Sci.

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Mechanical ventilation has significant therapeutic benefits, but it may cause or aggravate lung injury, which is called ventilator-induced lung injury (VILI). Endogenous hydrogen sulfide (H2S) has roles including regulating inflammation, and promoting vasodilatation; it also exhibits anti-oxidative stress and anti-fibrosis effects. H2S has been reported to alleviate lung injury, but the effects and mechanism of H2S on VILI remain unclear. The present study established a rat model of VILI and treated them with H2S, then measured the changes in respiratory function indicators, lung tissue histopathology, and oxidative, inflammatory, and apoptotic indicators. The effect of H2S on autophagy in the VILI model and the involvement of endoplasmic reticulum (ER) stress were also investigated. To further explore the mechanism, L2 alveolar epithelial cells were treated with cyclic strain to mimic mechanical strain along with the H2S donor NaHS, and the involvement of the NF-κB/MAPK signaling pathway was examined. The results showed that H2S significantly alleviated VILI and inhibited the inflammation and oxidative stress induced by VILI. H2S also significantly reduced autophagy and ER stress in rats. The phosphorylation of IRE1α, PERK and eIF2α and the expression of nuclear ATF4, and GADD34 in L2 cells were all significantly reduced with NaHS. Nuclear NF-κB p65, MAPK p38, JNK, and ERK were all activated by cyclic strain, but inhibited by the ER stress inhibitor 4-PBA or NaHS. Our findings revealed that H2S treatment alleviated VILI by regulating autophagy and ER stress, and the PERK/eIF2α/ATF4/GADD34 and NF-κB/MAPK pathways were involved in the underlying mechanism.

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“…It also includes increased vascular permeability, heterogeneous alveolar atelectasis and consolidated lung regions resulting in low ventilation to perfusion lung units, lung oedema, and progressive deterioration in FRC. Finally, the neonates and adults share a reduction in lung compliance and pulmonary artery hypertension when they develop acute respiratory distress [85,100,101].…”

Section: Surfactant and The Adult Population With And Without Ali/ardsmentioning

confidence: 99%

An overview of acute lung injury in general and in particular viral infections with specific reference to nebulized surfactant and anticoagulation

Smith¹,

Coetzee²,

Zyl³

2020

J Respir Dis Med

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The coronavirus 2 (SARS-CoV-2) has resulted in an international pandemic. The SARS-CoV-2 affects cardiovascular, digestive and urogenital systems. In an attempt to develop a multimodal and targeted approach to the pathophysiology associated with viral lung injury, we reviewed lung histopathology, inflammation, surfactant biology and pathophysiology related to viral associated acute lung injury (ALI / ARDS). Histopathology of viral pneumonia/ARDS cases of the past 100 years has revealed that lung parenchymal and vascular pathologic changes described in the 1918 influenza pandemic, are no different from the histopathology observed in other viral pandemics. Given the inflammatory storm which can occur in COVID-19 infection, the patient is a candidate to develop the classic multi-organ dysfunction and / or failure (MOD/F) which may well include ALI and ARDS. Because there is a well described temporal change in the pathophysiology associated with ALI /ARDS, a "one size fit al" remedy will not suffice, hence our attempt at a targeted functional approach. For instance, variable results in adults treated with surfactant have relegated the use of surfactant in adult ARDS to an uncertainty. We speculate that early and repeated surfactant installation in adults is required in adults. Surfactant may also have beneficial effects on the inflammatory process in the ARDS lung. The increased clotting tendency associated with the inflammation (and ARDS), particularly the effect on the lung vasculature (acute pulmonary hypertension and increased dead space), causes mechanical pressure overload (and failure) of the right ventricle and mechanical respiratory failure. Active management of these should include inhibition of the accelerated coagulation and thrombolysis (via nebulization) and early inotropic support.

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Computational models of ventilator induced lung injury and surfactant dysfunction

Cited by 8 publications

References 52 publications

Determination of rheology and surface tension of airway surface liquid: a review of clinical relevance and measurement techniques

Determination of rheology and surface tension of airway surface liquid: a review of clinical relevance and measurement techniques

Hydrogen sulfide treatment alleviated ventilator-induced lung injury through regulation of autophagy and endoplasmic reticulum stress

An overview of acute lung injury in general and in particular viral infections with specific reference to nebulized surfactant and anticoagulation

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