Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins

Schwingshackl, Andreas; López, Benjamín; Teng, Bo; Luellen, Charlean L.; Lesage, Florian; Belperio, John A.; Olcese, Riccardo; Waters, Christopher M.

doi:10.1152/ajplung.00121.2017

Cited by 26 publications

(24 citation statements)

References 132 publications

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“…As a result, high fractions of inspired oxygen (FiO 2 ) are commonly administered during this initial phase and may result in hyperoxemia on hospital admission. However, exposure to high oxygen levels, even during a short period of time, has been associated with cerebral and coronary vasoconstriction, deleterious effects on lung function, and increased production of reactive oxygen species [5][6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry

et al. 2020

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Background Hyperoxemia has been associated with increased mortality in critically ill patients, but little is known about its effect in trauma patients. The objective of this study was to assess the association between early hyperoxemia and in-hospital mortality after severe trauma. We hypothesized that a PaO2 ≥ 150 mmHg on admission was associated with increased in-hospital mortality. Methods Using data issued from a multicenter prospective trauma registry in France, we included trauma patients managed by the emergency medical services between May 2016 and March 2019 and admitted to a level I trauma center. Early hyperoxemia was defined as an arterial oxygen tension (PaO2) above 150 mmHg measured on hospital admission. In-hospital mortality was compared between normoxemic (150 > PaO2 ≥ 60 mmHg) and hyperoxemic patients using a propensity-score model with predetermined variables (gender, age, prehospital heart rate and systolic blood pressure, temperature, hemoglobin and arterial lactate, use of mechanical ventilation, presence of traumatic brain injury (TBI), initial Glasgow Coma Scale score, Injury Severity Score (ISS), American Society of Anesthesiologists physical health class > I, and presence of hemorrhagic shock). Results A total of 5912 patients were analyzed. The median age was 39 [26–55] years and 78% were male. More than half (53%) of the patients had an ISS above 15, and 32% had traumatic brain injury. On univariate analysis, the in-hospital mortality was higher in hyperoxemic patients compared to normoxemic patients (12% versus 9%, p < 0.0001). However, after propensity score matching, we found a significantly lower in-hospital mortality in hyperoxemic patients compared to normoxemic patients (OR 0.59 [0.50–0.70], p < 0.0001). Conclusion In this large observational study, early hyperoxemia in trauma patients was associated with reduced adjusted in-hospital mortality. This result contrasts the unadjusted in-hospital mortality as well as numerous other findings reported in acutely and critically ill patients. The study calls for a randomized clinical trial to further investigate this association.

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Section: Introductionmentioning

confidence: 99%

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry

et al. 2020

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“…Studies on mouse models have reported an association between hyperoxia and lung damage as a result of inflammation and oxidative stress [ 30 ], cell death [ 15 , 16 ], impairment of the surfactant system [ 15 , 17 ], and increased lung injury and mortality in pulmonary infections [ 18 , 19 ]. Hyperoxia caused a dose- and time-dependent inflammatory response in mechanically ventilated mice [ 20 ], and studies in critically ill patients have shown harmful effects of hyperoxia [ 22 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

García‐Laorden

Rodríguez-González

Martin‐Barrasa

et al. 2020

Mediators of Inflammation

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Supplemental oxygen is a supportive treatment in patients with sepsis to balance tissue oxygen delivery and demand in the tissues. However, hyperoxia may induce some pathological effects. We sought to assess organ damage associated with hyperoxia and its correlation with the production of reactive oxygen species (ROS) in a preclinical model of intra-abdominal sepsis. For this purpose, sepsis was induced in male, Sprague-Dawley rats by cecal ligation and puncture (CLP). We randomly assigned experimental animals to three groups: control (healthy animals), septic (CLP), and sham-septic (surgical intervention without CLP). At 18 h after CLP, septic ( n = 39 ), sham-septic ( n = 16 ), and healthy ( n = 24 ) animals were placed within a sealed Plexiglas cage and randomly distributed into four groups for continuous treatment with 21%, 40%, 60%, or 100% oxygen for 24 h. At the end of the experimental period, we evaluated serum levels of cytokines, organ damage biomarkers, histological examination of brain and lung tissue, and ROS production in each surviving animal. We found that high oxygen concentrations increased IL-6 and biomarkers of organ damage levels in septic animals, although no relevant histopathological lung or brain damage was observed. Healthy rats had an increase in IL-6 and aspartate aminotransferase at high oxygen concentration. IL-6 levels, but not ROS levels, are correlated with markers of organ damage. In our study, the use of high oxygen concentrations in a clinically relevant model of intra-abdominal sepsis was associated with enhanced inflammation and organ damage. These findings were unrelated to ROS release into circulation. Hyperoxia could exacerbate sepsis-induced inflammation, and it could be by itself detrimental. Our study highlights the need of developing safer thresholds for oxygen therapy.

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“…The inhalation of NO as a therapeutic strategy for hyperoxic lung injury is still controversial [ 74 ]. The surfactant system may also be impaired by hyperoxia with the downregulation of surfactant-associated protein [ 72 , 75 ], alveolar instability and a reduction in lung compliance, especially during ventilation with high tidal volumes [ 76 , 77 ].…”

Section: Clinical Implications Of Oxidative Stressmentioning

confidence: 99%

Biological effects of the oxygen molecule in critically ill patients

Nakane

2020

j intensive care

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The medical use of oxygen has been widely and frequently proposed for patients, especially those under critical care; however, its benefit and drawbacks remain controversial for certain conditions. The induction of oxygen therapy is commonly considered for either treating or preventing hypoxia. Therefore, the concept of different types of hypoxia should be understood, particularly in terms of their mechanism, as the effect of oxygen therapy principally varies by the physiological characteristics of hypoxia. Oxygen molecules must be constantly delivered to all cells throughout the human body and utilized effectively in the process of mitochondrial oxidative phosphorylation, which is necessary for generating energy through the formation of adenosine triphosphate. If the oxygen availability at the cellular level is inadequate for sustaining the metabolism, the condition of hypoxia which is characterized as heterogeneity in tissue oxygen tension may develop, which is called dysoxia, a more physiological concept that is related to hypoxia. In such hypoxic patients, repetitive measurements of the lactate level in blood are generally recommended in order to select the adequate therapeutic strategy targeting a reduction in lactate production. Excessive oxygen, however, may actually induce a hyperoxic condition which thus can lead to harmful oxidative stress by increasing the production of reactive oxygen species, possibly resulting in cellular dysfunction or death. In contrast, the human body has several oxygen-sensing mechanisms for preventing both hypoxia and hyperoxia that are employed to ensure a proper balance between the oxygen supply and demand and prevent organs and cells from suffering hyperoxia-induced oxidative stress. Thus, while the concept of hyperoxia is known to have possible adverse effects on the lung, the heart, the brain, or other organs in various pathological conditions of critically ill patients, and no obvious evidence has yet been proposed to totally support liberal oxygen supplementation in any subset of critically ill patients, relatively conservative oxygen therapy with cautious monitoring appears to be safe and may improve the outcome by preventing harmful oxidative stress resulting from excessive oxygen administration. Given the biological effects of oxygen molecules, although the optimal target levels remain controversial, unnecessary oxygen administration should be avoided, and exposure to hyperoxemia should be minimized in critically ill patients.

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Hyperoxia treatment of TREK-1/TREK-2/TRAAK-deficient mice is associated with a reduction in surfactant proteins

Cited by 26 publications

References 132 publications

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry

Early hyperoxemia is associated with lower adjusted mortality after severe trauma: results from a French registry

Systemic Effects Induced by Hyperoxia in a Preclinical Model of Intra-abdominal Sepsis

Biological effects of the oxygen molecule in critically ill patients

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