Role of shear stress in ventilator-induced lung injury

Jamaati, Hamidreza; Nazari, Milad; Darooei, Reza; Ghafari, Tara; Raoufy, Mohammad Reza

doi:10.1016/s2213-2600(16)30159-x

Cited by 15 publications

(8 citation statements)

References 5 publications

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“…Gattinoni et al [57] outlined the cascade in which mechanical strain activates macrophages and epithelial cells to produce interleukin-8, a cytokine that recruits neutrophils causing inflammation. Commenting on a recent clinical meta-analysis on the link between driving pressure and postoperative pulmonary complications [58], Jamaati et al [59] proposed that airflow-related shear stress may play a larger role in contributing to VILI than previously thought. Following our measurements of the high-momentum jet region in the trachea (figure 1) combined with the observation that HFV protocols using lower tidal volumes reduce its strength (figure 2), we explore the relationship between the jet phenomenon and airway WSS.…”

Section: Wall Shear Stress and Biotraumamentioning

confidence: 99%

Ventilation-induced jet suggests biotrauma in reconstructed airways of the intubated neonate

Nof

Heller-Algazi

Coletti

et al. 2020

J. R. Soc. Interface.

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We investigate respiratory flow phenomena in a reconstructed upper airway model of an intubated neonate undergoing invasive mechanical ventilation, spanning conventional to high-frequency ventilation (HFV) modes. Using high-speed tomographic particle image velocimetry, we resolve transient, three-dimensional flow fields and observe a persistent jet flow exiting the endotracheal tube whose strength is directly modulated according to the ventilation protocol. We identify this synthetic jet as the dominating signature of convective flow under intubated ventilation. Concurrently, our in silico wall shear stress analysis reveals a hitherto overlooked source of ventilator-induced lung injury as a result of jet impingement on the tracheal carina, suggesting damage to the bronchial epithelium; this type of injury is known as biotrauma. We find HFV advantageous in mitigating the intensity of such impingement, which may contribute to its role as a lung protective method. Our findings may encourage the adoption of less invasive ventilation procedures currently used in neonatal intensive care units.

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Section: Wall Shear Stress and Biotraumamentioning

confidence: 99%

Ventilation-induced jet suggests biotrauma in reconstructed airways of the intubated neonate

Nof

Heller-Algazi

Coletti

et al. 2020

J. R. Soc. Interface.

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“…In contrast, there has been little emphasis on the lungs' proximal regions (i.e., upper airways), where airflow dynamics are most prominent. Namely, the exposure of bronchial epithelial cells to respiratory flow‐induced shear stresses has been proposed as a potential link between large ventilation pressures and morbidity and mortality 25 ; a situation strongly correlated in ventilated patients undergoing surgery in the absence of prior lung injury 26 . In support, computational fluid dynamics (CFD)‐based in silico studies have found that upper airway flow phenomena and ensuing wall shear stresses (WSS) may contribute to ventilator‐induced lung injury (VILI) via the biotraumatic pathway 27–29 .…”

Section: Introductionmentioning

confidence: 99%

Ventilation‐induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with prophylactic anti‐inflammatory therapeutics

Nof

Artzy‐Schnirman

Bhardwaj

et al. 2021

Bioengineering & Transla Med

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Mortality rates among patients suffering from acute respiratory failure remain perplexingly high despite the maintenance of blood oxygen homeostasis during ventilatory support. The biotrauma hypothesis advocates that mechanical forces from invasive ventilation trigger immunological mediators that spread systemically. Yet, how these forces elicit an immune response remains unclear. Here, a biomimetic in vitro three‐dimensional (3D) upper airways model allows to recapitulate lung injury and immune responses induced during invasive mechanical ventilation in neonates. Under such ventilatory support, flow‐induced stresses injure the bronchial epithelium of the intubated airways model and directly modulate epithelial cell inflammatory cytokine secretion associated with pulmonary injury. Fluorescence microscopy and biochemical analyses reveal site‐specific susceptibility to epithelial erosion in airways from jet‐flow impaction and are linked to increases in cell apoptosis and modulated secretions of cytokines IL‐6, ‐8, and ‐10. In an effort to mitigate the onset of biotrauma, prophylactic pharmacological treatment with Montelukast, a leukotriene receptor antagonist, reduces apoptosis and pro‐inflammatory signaling during invasive ventilation of the in vitro model. This 3D airway platform points to a previously overlooked origin of lung injury and showcases translational opportunities in preclinical pulmonary research toward protective therapies and improved protocols for patient care.

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“…It has been extensively documented that the shear forces generated by mechanical ventilation exacerbate lung injury [17]. The characteristics of these lung injuries include the changes in lung structure.…”

Section: Damage Due To MVmentioning

confidence: 99%

Mechanical Ventilation induced DNA Damage and P21 in an Acute Aging Model of Lung Injury

Gninzeko

Tho

Valentine

et al. 2022

Preprint

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Acute respiratory distress syndrome (ARDS) is a form of acute lung injury which leads to a paucity of oxygen. To remedy ARDS, patients are put on mechanical ventilators; however, the stretch resulting from the mechanical ventilator can lead to ventilator-induced lung injury or VILI. VILI is exacerbated by age. The combined effects of ARDS and mechanical ventilation can result in a hostile environment which may lead to senescence (stable cell cycle arrest). The role of senescence in VILI is poorly understood. Senescence is characterized by increased cyclin-dependent kinase inhibitors P16 and P21; however, P21 has been shown to occur in early senescence. We hypothesized that mechanical ventilation would lead to DNA damage and senescence-like phenotype. Both in vivo and in vitro models of VILI were used to investigate senescence and its mechanism in VILI. Mechanical ventilation increased senescence-associated markers such as DNA damage marker characterized by γH2AX, P21, senescence-associated secretory phenotype IL6, and decreased proliferation. Moreover, mechanical ventilation led to increased apoptosis. Lung sections were stained for KRT8 proteins, markers of transiently differentiated alveolar type 2 (AT2) cells which were reported to be more prone to DNA damage. Age and mechanical ventilation increased KRT8 positive cells. Finally, we probed a potential mediator of the stretch-induced senescence in vitro by inhibiting P38-MAPK, which can be activated by DNA damage response, leading to increased P21. Inhibiting P38 decreased in P21 but did not decrease ɣH2AXThese findings suggest that mechanical ventilation may lead to a senescence-like phenotype involving the P38-MAPK pathway.

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Role of shear stress in ventilator-induced lung injury

Cited by 15 publications

References 5 publications

Ventilation-induced jet suggests biotrauma in reconstructed airways of the intubated neonate

Ventilation-induced jet suggests biotrauma in reconstructed airways of the intubated neonate

Ventilation‐induced epithelial injury drives biological onset of lung trauma in vitro and is mitigated with prophylactic anti‐inflammatory therapeutics

Mechanical Ventilation induced DNA Damage and P21 in an Acute Aging Model of Lung Injury

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