Spillover of Cytokines and Reactive Oxygen Species in Ventilator-Induced Lung Injury Associated With Inflammation and Apoptosis in Distal Organs

Liu, Yung Yang; Chiang, Chi Huei; Chuang, Chiao Hui; Liu, Shiou Ling; Jheng, Yi Han; Ryu, Jay H.

doi:10.4187/respcare.02992

Cited by 19 publications

(12 citation statements)

References 38 publications

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“…In the present model, we therefore first proved that moderate tidal volume ventilation induces oxidative stress. Similar to more recent reports in rodent VILI models, we observed a significant increase of RONS upon mechanical ventilation [ 19 , 33 – 35 ]. In contrast, supplemental H 2 S resulted in a complete prevention of RONS formation during ventilation.…”

Section: Discussionsupporting

confidence: 92%

Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury

Spassov

Donus

Ihle

et al. 2017

Oxidative Medicine and Cellular Longevity

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The development of ventilator-induced lung injury (VILI) is still a major problem in mechanically ventilated patients. Low dose inhalation of hydrogen sulfide (H2S) during mechanical ventilation has been proven to prevent lung damage by limiting inflammatory responses in rodent models. However, the capacity of H2S to affect oxidative processes in VILI and its underlying molecular signaling pathways remains elusive. In the present study we show that ventilation with moderate tidal volumes of 12 ml/kg for 6 h led to an excessive formation of reactive oxygen species (ROS) in mice lungs which was prevented by supplemental inhalation of 80 parts per million of H2S. In addition, phosphorylation of the signaling protein Akt was induced by H2S. In contrast, inhibition of Akt by LY294002 during ventilation reestablished lung damage, neutrophil influx, and proinflammatory cytokine release despite the presence of H2S. Moreover, the ability of H2S to induce the antioxidant glutathione and to prevent ROS production was reversed in the presence of the Akt inhibitor. Here, we provide the first evidence that H2S-mediated Akt activation is a key step in protection against VILI, suggesting that Akt signaling limits not only inflammatory but also detrimental oxidative processes that promote the development of lung injury.

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Section: Discussionsupporting

confidence: 92%

Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury

Spassov

Donus

Ihle

et al. 2017

Oxidative Medicine and Cellular Longevity

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“… 5 , 8 Early onset proinflammatory cytokines such as TNF-α, IL-6, or IL-1 are the predominant mediators of the disease and are involved in the course of lung injury. 9 , 35 TNF-α is known to alter pulmonary membrane permeability, to trigger leukocyte recruitment, and to initiate downstream effects of inflammation in the lung. 6 , 7 , 9 In the present study, there was a significant induction of proinflammatory cytokines on both the mRNA and the protein levels.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

Menk¹,

Graw²,

Haefen³

et al. 2018

JIR

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PurposeAlthough the role of the angiotensin II type 2 (AT2) receptor in acute lung injury is not yet completely understood, a protective role of this receptor subtype has been suggested. We hypothesized that, in a rodent model of acute lung injury, stimulation of the AT2 receptor with the direct agonist Compound 21 (C21) might have a beneficial effect on pulmonary inflammation and might improve pulmonary gas exchange.Materials and methodsMale adult rats were divided into a treatment group that received pulmonary lavage followed by mechanical ventilation (LAV, n=9), a group receiving pulmonary lavage, mechanical ventilation, and direct stimulation of the AT2 receptor with C21 (LAV+C21, n=9), and a control group that received mechanical ventilation only (control, n=9). Arterial blood gas analysis was performed every 30 min throughout the 240-min observation period. Lung tissue and plasma samples were obtained at 240 min after the start of mechanical ventilation. Protein content and surface activity of bronchoalveolar lavage fluid were assessed and the wet/dry-weight ratio of lungs was determined. Transcriptional and translational regulation of pro- and antiinflammatory cytokines IL-1β, tumor necrosis factor-alpha, IL-6, IL-10, and IL-4 was determined in lungs and in plasma.ResultsPulmonary lavage led to a significant impairment of gas exchange, the formation of lung edema, and the induction of pulmonary inflammation. Protein content of lavage fluid was increased and contained washed-out surfactant. Direct AT2 receptor stimulation with C21 led to a significant inhibition of tumor necrosis factor-alpha and IL-6 expressions in the lungs, whereas the expressions of IL-1, IL-10, and IL-4 remained unchanged. During the 240-min observation period, AT2 receptor stimulation did not improve pulmonary gas exchange or lung edema.ConclusionIn this rodent model of acute lung injury after repeated pulmonary lavage, AT2 receptor stimulation attenuates pulmonary inflammation but does not improve gas exchange.

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“…Finally, VILI has longer-term consequences than simply physical damage to and repair of the components of the blood-gas barrier. The upregulation of inflammatory mediators as a result of this damage can be extensive when injury is widespread and severe (106)(107)(108)(109)(110)(111), and can itself have adverse downstream consequences for other parts of the body. Indeed, multi-organ failure resulting from an overwhelming inflammatory response of this nature, known as biotrauma (112), is frequently the ultimate cause of death in ARDS (16).…”

Section: Mechanisms Of Vilimentioning

confidence: 99%

Ventilator-induced lung injury and lung mechanics

Bates

Smith

2018

Ann. Transl. Med

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Mechanical ventilation applies physical stresses to the tissues of the lung and thus may give rise to ventilator-induced lung injury (VILI), particular in patients with acute respiratory distress syndrome (ARDS). The most dire consequences of VILI result from injury to the blood-gas barrier. This allows plasma-derived fluid and proteins to leak into the airspaces where they flood some alveolar regions, while interfering with the functioning of pulmonary surfactant in those regions that remain open. These effects are reflected in commensurately increased values of dynamic lung elastance (E L), a quantity that in principle is readily measured at the bedside. Recent mathematical/computational modeling studies have shown that the way in which E L varies as a function of both time and positive end-expiratory pressure (PEEP) reflects the nature and degree of lung injury, and can even be used to infer the separate contributions of volutrauma and atelectrauma to VILI. Interrogating such models for minimally injurious regimens of mechanical ventilation that apply to a particular lung may thus lead to personalized approaches to the ventilatory management of ARDS.

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Spillover of Cytokines and Reactive Oxygen Species in Ventilator-Induced Lung Injury Associated With Inflammation and Apoptosis in Distal Organs

Cited by 19 publications

References 38 publications

Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury

Hydrogen Sulfide Prevents Formation of Reactive Oxygen Species through PI3K/Akt Signaling and Limits Ventilator-Induced Lung Injury

Angiotensin II type 2 receptor agonist Compound 21 attenuates pulmonary inflammation in a model of acute lung injury

Ventilator-induced lung injury and lung mechanics

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