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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Administration of inhaled nitric oxide (iNO) is a potential therapeutic strategy to prevent bronchopulmonary dysplasia (BPD) in premature newborns with respiratory distress syndrome. We evaluated this approach in a rat model, in which premature pups were exposed to room air, hyperoxia, or a combination of hyperoxia and NO (8.5 and 17 ppm). We investigated the anti-inflammatory effects of prolonged iNO therapy by studying survival, histopathology, fibrin deposition, and differential mRNA expression (real-time RT-PCR) of key genes involved in the development of BPD. iNO therapy prolonged median survival 1.5 days (P = 0.0003), reduced fibrin deposition in a dosage-dependent way up to 4.3-fold (P < 0.001), improved alveolar development by reducing septal thickness, and reduced the influx of leukocytes. Analysis of mRNA expression revealed an iNO-induced downregulation of genes involved in inflammation (IL-6, cytokine-induced neutrophilic chemoattractant-1, and amphiregulin), coagulation, fibrinolysis (plasminogen activator inhibitor 1 and urokinase-type plasminogen activator receptor), cell cycle regulation (p21), and an upregulation of fibroblast growth factor receptor-4 (alveolar formation). We conclude that iNO therapy improves lung pathology and prolongs survival by reducing septum thickness, inhibiting inflammation, and reducing alveolar fibrin deposition in premature rat pups with neonatal hyperoxic lung injury.
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PMID:Inhaled nitric oxide attenuates pulmonary inflammation and fibrin deposition and prolongs survival in neonatal hyperoxic lung injury. 1738 81

Our previous work has shown that adult mice with overexpression of IL-6 and IL-13 in the lung have enhanced survival in hyperoxia associated with reduced hyperoxia-induced lung injury and cell death. We hypothesized that there are developmental differences in these responses in the adult vs. the newborn (NB) animal, and these responses have clinical relevance in the human NB. We compared the responses to 100% O(2) of NB IL-6 and IL-13 transgenic mice with wild-type littermate controls by evaluating mortality, lung tissue TUNEL staining, and mRNA expression using RT-PCR. We used ELISA to measure IL-6 levels in tracheal aspirates from human neonates. Our results show that, in contrast to the cytoprotective effects in mature mice, IL-6 caused significantly increased mortality, DNA injury, caspases, cell death regulator and angiogenic factor expression in hyperoxia in the NB. Furthermore, tracheal aspirate levels of IL-6 were significantly increased in premature neonates with respiratory distress syndrome who had an adverse outcome (bronchopulmonary dysplasia/death). In contrast to the protective effects in adults, there was no survival advantage to the NB IL-13 mice in hyperoxia. These findings imply that caution should be exercised in extrapolating results from the adult to the NB.
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PMID:Developmental differences in the responses of IL-6 and IL-13 transgenic mice exposed to hyperoxia. 1740 Jun

In patients with acute respiratory distress syndrome (ARDS), supportive therapy with mechanical ventilation and oxygen is often life saving. Further acute lung injury however, is an unfortunate consequence of oxygen therapy as well as mechanical injury secondary to ventilator induced/associated lung injury (VI/ALI). In this issue of Critical Care, Li et al. expand on the intra-cellular signaling pathways regulating interactions between injury cascades resulting from hyperoxia and high tidal volume ventilation. The findings, suggest that interference or cooperation of different signals may have critical consequences as evidenced by indices of increased lung inflammation, microvascular permeability, and lung epithelial apoptotic cell death.
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PMID:Hyperoxic acute lung injury and ventilator-induced/associated lung injury: new insights into intracellular signaling pathways. 1731 25

Assisted ventilation is necessary for treating preterm infants with respiratory distress syndrome. Unfortunately, high and prolonged concentrations of oxygen associated with assisted ventilation often lead to pulmonary changes, such as hemorrhage and inflammation. The resulting chronic pulmonary condition is known as bronchopulmonary dysplasia. Pulmonary changes characteristic of this syndrome can be produced in rat pups exposed to high oxygen levels. We exposed 21-d-old rats to room air or continuous 95% oxygen for 7 d and then allocated them into 6 groups to evaluate whether treatment with zileuton and zafirlukast, 2 agents which decrease the effects of leukotrienes, lessened the pulmonary effects of short-term hyperoxia. After 7 d, lung tissue was collected for light and electron microscopy. Pulmonary changes including edema, hemorrhage, alveolar macrophage influx, and Type II pneumocyte proliferation were graded on a numerical scoring system. Compared with controls exposed to hyperoxia [corrected] and saline, rats exposed to hyperoxia and treated with zileuton had significantly reduced levels of alveolar macrophage influx and Type II pneumocyte proliferation, but those exposed to hyperoxia [corrected] and treated with zafirlukast showed no significant reduction in any pulmonary changes. This study helps define pulmonary changes induced secondary to hyperoxia in rat pups and presents new information on the mechanisms of leukotriene inhibition in decreasing the severity of hyperoxic lung injury.
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PMID:Effects of leukotriene inhibition on pulmonary morphology in rat pup lungs exposed to hyperoxia. 1753 19

Patients with acute respiratory distress syndrome undergoing mechanical ventilation may be exposed to both high levels of stretch and high levels of oxygen. We hypothesized that the combination of high stretch and hyperoxia promotes loss of epithelial adhesion and impairs epithelial repair mechanisms necessary for restoration of barrier function. We utilized a model of high tidal volume mechanical ventilation (25 ml/kg) with hyperoxia (50% O(2)) in rats to investigate alveolar type II (AT2) cell adhesion and focal adhesion signaling. AT2 cells isolated from rats exposed to hyperoxia and high tidal volume mechanical ventilation (MVHO) exhibited significantly decreased cell adhesion and reduction in phosphotyrosyl levels of focal adhesion kinase (FAK) and paxillin compared with control rats, rats exposed to hyperoxia without ventilation (HO), or rats ventilated with normoxia (MV). MV alone increased phosphorylation of p130(Cas). RhoA activation was increased by MV, HO, and the combination of MV and HO. Treatment of MVHO cells with keratinocyte growth factor (KGF) for 1 h upon isolation reduced RhoA activity and restored attachment to control levels. Attachment and migration of control AT2 cells was significantly decreased by constitutively active RhoA or a kinase inactive form of FAK (FRNK), whereas expression of dominant negative RhoA in cells from MVHO-treated rats restored cell adhesion. Mechanical ventilation with hyperoxia promotes changes in focal adhesion proteins and RhoA in AT2 cells that may be deleterious for cell adhesion and migration.
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PMID:High tidal volume mechanical ventilation with hyperoxia alters alveolar type II cell adhesion. 1760 98

Apoptosis has been considered as an underlying mechanism in acute lung injury/acute respiratory distress syndrome and multiorgan dysfunction syndrome. Recently, several alternative pathways for cell death (such as caspase-independent cell death, oncosis, and autophagy) have been discovered. Evidence of these pathways in the pathogenesis of acute lung injury has also come into light. In this article, we briefly introduce cell death pathways and then focus on studies related to lung injury. The different types of cell death that occur and the underlying mechanisms utilized depend on both experimental and clinical conditions. Lipopolysaccharide-induced acute lung injury is associated with apoptosis via Fas/Fas ligand mechanisms. Hyperoxia and ischemia-reperfusion injury generate reactive oxidative species, which induce complex cell death patterns composed of apoptosis, oncosis, and necrosis. Prolonged overexpression of inflammatory mediators results in increased production and activation of proteases, especially cathepsins. Activation and resistance to death of neutrophils also plays an important role in promoting parenchymal cell death. Knowledge of the coexisting multiple cell death pathways and awareness of the pharmacological inhibitors targeting different proteases critical to cell death may lead to the development of novel therapies for acute lung injury.
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PMID:Acute lung injury and cell death: how many ways can cells die? 1820 16

Increased levels of interleukin (IL)-8 and monocyte chemoattractant protein (MCP)-1 have been found in bronchoalveolar lavage fluid of acute respiratory distress syndrome (ARDS) patients. The authors investigated whether inflammatory-activated microvascular pulmonary endothelial cells (HMVECL) regulate expression of IL-8 and MCP-1 in the alveolar epithelial cell line A549 and studied the effects of hypoxia (5% O(2)) and hyperoxia (85% O(2)). The authors observed significant up-regulation of IL-8 and MCP-1 expression in A549 cells that was independent from the IL-1 receptor pathway but was modified by oxygen tension. These data show that the pulmonary microvascular endothelium is able to regulate epithelial cell chemokine expression in a paracrine fashion.
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PMID:Inflammatory-activated microvascular endothelial cells regulate interleukin-8 and monocyte chemoattractant protein-1 expression of A549 cells in a paracrine fashion. 1826 31

There is many evidence that inhalation of high oxygen concentration has a toxic influence on pulmonary function and structures. Hyperoxia-induced oxidative stress is well characterized in rodents and has been used as a valuable model of human respiratory distress syndrome. We have previously shown that hyperoxic exposure of guinea pigs is associated with suppression of cough reflex. The goal of this study was to determine the effects of dietary intake of antioxidant flavonoids (Flavin7, Vita Crystal Slovakia Ltd., 2 ml/kg b.w.) on hyperoxia-induced oxidative stress in lung tissue directed on cough reflex. The experimental group (n = 8) was pretreated with Flavin7 as a single daily dose for 14 days and subsequently exposed to 100% 02 for 60 h. Hyperoxic group (n = 8) inhaled 100% Oz only. Control group (n = 8) was exposed to normoxia. Cough was induced by inhalation of citric acid aerosol at time before and after exposure to hyperoxia. Cough was also induced by mechanical stimulation of airways in anaesthetized animals just after the end of oxygen exposition. When to compare animal groups before and after hyperoxia, our results have shown a significant decrease 2 (1-6) vs 6 (4-6) p = 0.041 in citric acid-induced cough in hyperoxic animals and no significant changes 8 (5.5-8.5) vs 5 (4-6.5) p = 0.055 in animals with antioxidant therapy. Mechanically-induced cough after hyperoxia was not influenced by substitution with flavonoids. In conclusion, our results indicate that flavonoids attenuated hyperoxia-induced down-regulation especially of chemically-induced cough (Tab. 2, Fig. 2, Ref. 30). Full Text (Free, PDF) www.bmj.sk.
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PMID:Dietary intake of flavonoids and hyperoxia-induced oxidative stress related cough in guinea pigs. 1830 37

Elevated level of oxygen (hyperoxia) is widely used in critical care units and in respiratory insufficiencies. In addition, hyperoxia has been implicated in many diseases such as bronchopulmonary dysplasia or acute respiratory distress syndrome. Although hyperoxia is known to cause DNA base modifications and strand breaks, the DNA damage response has not been adequately investigated. We have investigated the effect of hyperoxia on DNA damage signaling and show that hyperoxia is a unique stress that activates the ataxia telangiectasia mutant (ATM)- and Rad3-related protein kinase (ATR)-dependent p53 phosphorylations (Ser6, -15, -37, and -392), phosphorylation of histone H2AX (Ser139), and phosphorylation of checkpoint kinase 1 (Chk1). In addition, we show that phosphorylation of p53 (Ser6) and histone H2AX (Ser139) depend on both ATM and ATR. We demonstrate that ATR activation precedes ATM activation in hyperoxia. Finally, we show that ATR is required for ATM activation in hyperoxia. Taken together, we report that ATR is the major DNA damage signal transducer in hyperoxia that activates ATM.
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PMID:Differential roles of ATR and ATM in p53, Chk1, and histone H2AX phosphorylation in response to hyperoxia: ATR-dependent ATM activation. 1834 16

Exogenous surfactant is critical in the treatment of neonates with respiratory distress syndrome. Lucinactant (Surfaxin; Discovery Laboratories, Inc.) is a surfactant replacement therapy containing sinulpeptide, which may reduce lung inflammation. This study tested whether Lucinactant reduces markers of inflammation, damage and remodeling in human airway epithelial cells exposed to hyperoxia. Calu-3 monolayers cultured at an air-liquid interface were treated apically with 140 microL of normal saline, Lucinactant or Beractant (Survanta; Abbott Laboratories, Inc.). Treated monolayers were exposed to 60% O(2)/5% CO(2) for 24 or 72 h. Transepithelial resistance (TER; p < 0.001) and cell viability (p < 0.05) were greater in both surfactant groups compared with saline; by 72 h Lucinactant cells had greater TER than Beractant (p < 0.001). Surfactant treated groups secreted less IL-8 than saline (p < 0.001), whereas Lucinactant cells secreted less IL-6 than saline and Beractant (p < 0.001). Matrix metalloproteinase 7, expressed by saline and Beractant treated cells at 24 h, was attenuated by 72 h by Beractant (p < 0.001), but was never detected in Lucinactant cells. Histology indicated less injury with Lucinactant relative to Beractant and saline. These data suggest that Lucinactant was protective compared with Beractant and control.
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PMID:KL4-surfactant (Lucinactant) protects human airway epithelium from hyperoxia. 1839 44


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