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

Hyperoxia is commonly used in the treatment of newborn respiratory distress. Although essential and life saving, oxygen therapy can result in the development of lung injury. Oxygen toxicity is associated with the production of reactive oxidant species. Nitric oxide (NO) is an oxidant formed by the catalysis of L-arginine when acted upon by the enzyme nitric oxide synthase (NOS). We studied the differential effects of prolonged normobaric hyperoxia (FIO2 = .95, for 3, 4, and 5 days) on the two major NOS enzymes, constitutive endothelial cell NOS (ecNOS) and inducible NOS (iNOS). Hyperoxia led to a significant lung injury, as measured by pulmonary compliance studies. Hyperoxia did not increase serum NO production, measured as the concentration of nitrite and nitrate. However, hyperoxia did result in a small but significant increase in NO production in the bronchoalveolar lavage fluid, as measured by the products of nitrite and nitrate concentration. This increase in NO was not associated with an induction of whole lung iNOS, as measured by the conversion of L-[3H]arginine to L-[3H]citrulline or by Northern blot analysis. Hyperoxia significantly decreased ecNOS activity as measured by the conversion of L-[3H]arginine to L-[3H]citrulline. In addition, administration of the NOS inhibitor NG-nitro-L-arginine methyl ester worsened the injury, as measured by lung compliance and survival. Further studies need to be performed to determine whether this decrease in ecNOS activity during hyperoxia plays a role in the pathogenesis of hyperoxia-related lung injury.
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PMID:Differential effects of hyperoxia on the inducible and constitutive isoforms of nitric oxide synthase in the lung. 916 69

Airway hyperreactivity is recognized as one of the long-term sequelae of bronchopulmonary dysplasia (BPD). Due to the improved care and prognosis of very low-birth weight infants, the incidence of BPD is increasing. There are data that suggest the increased survival of premature infants may be associated with the observed increased incidence of childhood asthma. The hyperoxia received as part of the treatment of respiratory distress syndrome is believed to be partly if not completely responsible for BPD. To gain insight into the potential role that hyperoxia might play in producing airway hyperreactivity, 4-day-old guinea pig pups were exposed to 70% oxygen or air for 96 h, and airway responsiveness to acetylcholine (ACh) was assessed both 2 and 9 days after the completion of the hyperoxia exposures. Unlike ozone, the mechanism for the persistently increased airway reactivity is not related either to the inhibition of neuronal acetylcholinesterase or inhibition of the neuronal M2 muscarinic receptor. A difference in antioxidant protection did not account for the increased response of the neonatal guinea pigs compared with hyperoxia-exposed rat pups. These data support the usefulness of the neonatal guinea pig as a model to study the mechanism responsible for hyperoxia-induced airway hyperreactivity.
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PMID:Airway hyperreactivity produced by short-term exposure to hyperoxia in neonatal guinea pigs. 922 25

Acute respiratory distress syndrome is a serious sequelae of many serious illnesses during pregnancy. An understanding of acute respiratory distress syndrome is central to the proper care of a patient with the disorder. Acute respiratory distress syndrome results in diminished pulmonary compliance and respiratory shunt mediated hypoxemia. Furthermore, the initial pulmonary injury in acute respiratory distress syndrome may be further worsened by therapeutic hyperoxia and barotrauma. Limitation of peak-plateau airway pressure to less than 35 to 40 cm H2O may reduce barotrauma. Inflammatory mediator therapy may hold future promise in attenuation of lung injury induced by acute respiratory distress syndrome. Aggressive care may help those pregnant patients afflicted with acute respiratory distress syndrome.
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PMID:Acute respiratory distress syndrome in pregnancy. 929 21

Although the antioxidant properties of N-acetylcysteine (NAC) in vitro are widely accepted, the efficacy of NAC in the prevention of O2 toxicity in vivo is poorly documented. The aim of our study was to investigate the presumed protective effect of NAC on hyperoxic lung injury, focusing on gamma-glutamyltransferase (gamma-GT) activity and glutathione (GSH) levels in lung tissue, epithelial lining fluid (ELF), and isolated rat type II cells immediately after their isolation and 48 h later when kept in culture in normoxia. Thirty-four male Wistar rats were divided in three groups (n = 10-14) and were exposed to air or to 60 or 85% O2 for 7 days. One-half of the rats in each group received 200 mg/kg NAC intraperitoneally one time per day from 3 days before exposure until the end of the experiment, and the other one-half received the vehicle. In the 85% O2-exposed animals, NAC led to more respiratory distress and weight loss. NAC did not prevent the rise in bronchoalveolar lavage lactate dehydrogenase and alkaline phosphatase, but it did prevent the rise in calculated ELF volume. NAC decreased GSH levels (1.4-fold) and gamma-GT activity (1.8-fold) in the air-exposed type II cells. In the 60% O2-exposed group, no effects of NAC were seen (except for a decrease in gamma-GT mRNA expression), but, in the 85% O2-exposed group, NAC gave rise to higher GSH (2.6-fold) and higher gamma-GT activity (2.9-fold) in the ELF and lower GSH (6.9-fold) and higher gamma-GT activity (3.6-fold) in the type II cells. Even in culture, GSH levels remained 1.5-fold lower than in the cells from the air-exposed animals and 2-fold lower than in the cells from the 85% O2-exposed animals. There was increased DNA damage (as assessed by thymidine incorporation) and apoptosis after hyperoxia, especially after 60% O2, and this effect was amplified after NAC treatment. Although protective at the endothelial side, NAC treatment led to adverse effects at the epithelial side, despite, or probably because of, restoration of the ELF GSH levels in the presence of high O2 levels. Because NAC is rapidly metabolized to cysteine, it is plausible that the effects of NAC are manifested through the toxic effects of cysteine.
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PMID:N-acetylcysteine does not protect against type II cell injury after prolonged exposure to hyperoxia in rats. 931 88

Surfactant dysfunction constitutes an important element in the complex pathophysiology of acute respiratory distress syndrome (ARDS). In this disease, surfactant may become inactivated by plasma proteins leaking into the airspaces as a consequence of increased alveolar permeability. In addition, surfactant proteins may become degraded by proteolytic enzymes or free oxygen radicals released by inflammatory cells recruited to the airspaces. Regardless of the mechanism involved, surfactant inactivation or degradation may be counterbalanced by increasing the pool of surfactant in the airspaces, i.e., by replacement therapy. Surfactant therapy has been tested with promising results in animal models of ARDS triggered by, e.g., lung lavage, hyperoxia or exposure to various toxic agents. In general, the response to surfactant treatment depends on the quality of the surfactant, timing of treatment in relation to the degree of lung injury, dosage and mode of administration. Encouraging results have been obtained with modified natural surfactants in clinical pilot studies on patients with ARDS, justifying further evaluation of this therapeutic approach in randomized controlled trials.
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PMID:Surfactant inactivation and surfactant therapy in acute respiratory distress syndrome (ARDS). 963 10

Lung injury is a frequent consequence of oxygen (O2) therapy administered to newborns and adults with respiratory distress. Acute exposure to hyperoxia results in a well-described pathophysiologic response in the lungs. Because inflammation is an important component of pulmonary O2 toxicity, we have an interest in identifying the inflammatory mediators that increase during hyperoxia. Platelet-endothelial cell adhesion molecule-1 (PECAM-1), a member of the immunoglobulin superfamily that is expressed at the junctions between endothelial cells, is essential to the transendothelial migration of leukocytes. We hypothesized that increased expression of PECAM-1 occurs in pulmonary endothelial cells during hyperoxic lung injury. Adult mice were exposed to 100% O2 for up to 96 h. We analyzed PECAM-1 expression by RNA blot hybridization, in situ hybridization, and immunohistochemistry. A increase in PECAM-1 mRNA was seen as soon as 2 d of hyperoxia relative to unexposed control mice. PECAM-1 mRNA and protein were found in endothelial cells of both large and small arteries. The expression of PECAM-1 in capillary vessels was further confirmed using in situ hybridization at the electron microscope level. This increase in PECAM-1 expression coincided with the appearance of leukocytes in lung tissue. These observations suggest that PECAM-1 expression is a relatively early step in the inflammation cascade, and intervention at this phase may be critical to the prevention of further damage.
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PMID:Increased endothelial cell expression of platelet-endothelial cell adhesion molecule-1 during hyperoxic lung injury. 976 50

Depletion of glutathione, a key antioxidant, accelerates lung injury. Glutathione concentrations are reduced significantly in premature infants with respiratory distress syndrome, leaving them at greater risk of bronchopulmonary dysplasia. A study was designed to verify if the increased glutathione synthetic activity observed in oxygen-dependent and ventilated newborn infants was caused by their postsurgical state. Our objective was to evaluate the role of a general surgical procedure as a factor affecting lung glutathione. One-day-old guinea pig pups, a well characterized animal model for the study of neonatal lung disease, were divided between those undergoing a standardized surgical procedure and those that did not. The pups were fed by their mother. After 4 days the lungs were sampled to determine total glutathione content, activities of gamma-glutamyltranspeptidase, glutathione peroxidase, and reductase as well as the glutathione synthetic activity. The surgical procedure was associated with a specific stimulatory effect limited to glutathione synthetic activity (p < 0.02) leading to an increased (p < 0.02) pulmonary glutathione content. Glutathione concentration was significantly correlated (r2 = 0.67) with the synthetic activity. We concluded that in this animal model an invasive procedure such as a general surgical procedure affects lung glutathione metabolism in a fashion similar to that of hyperoxia. In the lungs, the synthetic activity is a stronger determinant of glutathione concentrations than the activities of the other enzymes involved in maintaining glutathione levels.
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PMID:Glutathione synthetic activity in the lungs in newborn guinea pigs. 983 29

Patients treated with bleomycin (BLM) are at risk of developing acute respiratory distress syndrome (ARDS) post-operatively, and this has been associated with high intraoperative concentrations of oxygen. We report progressive arterial desaturation noticeable 2 h after the start of a 4-h radical neck dissection for which the anaesthesia included 50% O2 in N2O. The patient had received two courses of bleomycin within the previous 2 months and had undergone an uneventful right hemiglossectomy under shorter but otherwise similar anaesthesia 4 weeks previously. His pulmonary function tests before the second procedure showed a slight depression of diffusing capacity (DLco) to 80% of predicted and minimal airway obstruction consistent with his history of smoking. The pulse oximetric reading during his second procedure reached 75%, but rose to 95% after treatment with methylprednisolone salbutamol and inspired O2 concentrations between 80% and 100%. By the end of the procedure, he satisfied the criteria for ARDS and was transferred to the ICU, where he developed bilateral pneumonia, deteriorated and died of multiple organ failure. This case suggests that the risk of hyperoxic pulmonary damage in patients exposed to bleomycin may increase not only with the degree and duration of hyperoxia in a given exposure, but also with the latent effects of recent previous exposure. Near normality of pulmonary function tests cannot be taken as reassurance, and small changes may have more adverse prognostic significance than in patients who have not been exposed to bleomycin.
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PMID:Intraoperative respiratory failure in a patient after treatment with bleomycin: previous and current intraoperative exposure to 50% oxygen. 1008 4

Frequency and perinatal risk factors in bronchopulmonary dysplasia (BPD) were retrospectively evaluated in a cohort of 242 infants with birth weights less than 1501 g born in one hospital in 1990-1994. At 28 days' postnatal age, 30.7% (59/192) of the infants alive received oxygen supplementation and showed typical radiological changes in chest X-rays. At 36 weeks' corrected gestation, 13.0% (24/184) of the survivors fulfilled these criteria. In multivariate analysis, low birth weight and gestational age, male sex, packed red cell infusions and long duration of ventilator therapy were correlated with an increased risk of BPD at 28 days' postnatal age. Only 49% of the infants with BPD had had respiratory distress syndrome, and 49% of them recovered from BPD by 36 weeks' corrected gestational age. Preeclampsia, low birth weight, rapid birth weight recovery, packed red cell infusions, long duration of ventilator therapy, patent ductus arteriosus and hyperoxia were associated with BPD beyond 36 weeks' corrected gestation. No infant born small for gestational age recovered from BPD before 36 weeks' corrected gestation. The frequency of BPD at 28 days' postnatal age seems to be increasing, but half of the patients recover before term. Factors other than respiratory distress syndrome, especially small birth weight, early weight gain and possibly intrauterine growth retardation are becoming more important risk factors of BPD beyond 36 weeks' corrected gestation.
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PMID:Frequency and risk factors in bronchopulmonary dysplasia in a cohort of very low birth weight infants. 1032 91

Superoxide formation in pulmonary tissue is modulated by cytokines, PO2, shear force, and disease states, and can be stimulated by drugs. Superoxide has diverse actions on pulmonary cells, including smooth muscle contraction, interaction with redox enzymes, cell proliferation, and gene transcription. In the lungs, there is an impressive array of specific defence mechanisms that destroy superoxide, especially superoxide dismutase (SOD) and metallothionein. Superoxide formation is increased in hyperoxia (e.g., oxygen therapy); however, superoxide-forming enzymes also can be up-regulated in hypoxia. Superoxide has been implicated in acute respiratory distress syndrome, lung ischaemia-reperfusion injury, and lung transplantation. Novel approaches to therapy have been explored, including SOD gene therapy and SOD targeting to the lung. In the future, new drugs interacting with superoxide may provide significant advances in the treatment of lung diseases.
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PMID:Superoxide in the pulmonary circulation. 1066 34


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