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

When exposed continuously to hyperoxia (100% O2, 760 Torr barometric pressure), rats pretreated with polyethylene glycol (PEG)-attached superoxide dismutase and catalase (PEG-SOD + PEG-CAT) lived longer (79.1 + 7.6 h) than rats pretreated with saline (60.7 +/- 2.1 h) or PEG-inactivated-SOD + PEG-inactivated-CAT (62.3 +/- 1.6 h). Rats pretreated with PEG-SOD + PEG-CAT also had less hyperoxia-induced acute oxidative edematous lung injury, as assessed by increases in lung oxidized glutathione (GSSG) contents, pleural effusions, and lung lavage albumin concentrations than saline-pretreated rats. Rats pretreated with the long-lived conjugates PEG-inactivated-SOD + PEG-inactivated-CAT or PEG-albumin also had decreased acute oxidative edematous lung injury compared with rats pretreated with PEG, SOD + CAT + PEG, SOD + CAT, or saline. In vitro studies suggested that PEG itself may have contributed to protection by scavenging hydroxyl radical (.OH) but not superoxide (O2-.) or H2O2. Compared with more effective endogenous (via preexposure to hypoxia) or exogenous (via liposomes) means for increasing lung antioxidant enzymes, PEG enzymes are less protective against lung injury from continuous hyperoxia.
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PMID:Polyethylene glycol-attached antioxidant enzymes decrease pulmonary oxygen toxicity in rats. 254 Jan 39

The role of neutrophils in the mediation of severe normobaric hyperoxic lung injury has been studied by monitoring the effects of neutrophil depletion on a rat model of pulmonary oxygen toxicity. Pulmonary capillary permeability, assessed using an [125I]albumin lung permeability index (LPI), progressively increased with an increased duration of hyperoxia exposure in normal animals (LPI = 0.43 +/- 0.09 at 24 h; 0.95 +/- 0.17 at 48 h; 1.56 +/- 0.21 at 60 h), despite the absence of any significant tissue or bronchoalveolar lavage evidence of neutrophil infiltration until 60 h of hyperoxia exposure. Neutrophil depletion (using cyclophosphamide) blocked this late neutrophil infiltrate but failed to attenuate lung injury (LPI = 0.38 +/- 0.06 at 24 h; 0.89 +/- 0.16 at 48 h; 1.58 +/- 0.10 at 60 h; all p greater than .05 compared with leucocyte-replete/normal animals exposed to hyperoxia). The temporal dissociation of pulmonary neutrophil accumulation and pulmonary injury and the failure of effective neutrophil depletion to abrogate hyperoxic lung injury indicate that neutrophil polymorphs play no substantive role in the mediation of tissue injury in this model of severe pulmonary oxygen toxicity.
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PMID:Granulocyte independence of pulmonary oxygen toxicity in the rat. 274 54

Experiments were conducted on rats to study systemic hemodynamics, microcirculation, and oxygen regimen in the organism in replacement of massive blood loss with albumin solution in normo- and hyperoxia. The results suggest that in breathing oxygen conditions are created in the organism for fuller realization of the mechanism of compensatory increase of the minute circulation volume in replacement of blood loss by a blood substitute, as a result of which total oxygen consumption increases and microcirculation is restored more adequately.
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PMID:[Effect of hyperoxia on systemic hemodynamics, microcirculation, and oxygen regimen in rats in replacement of massive blood loss by albumin]. 275 22

Neonatal lung injury from hyperoxia and mechanical hyperventilation was studied in newborn piglets hyperventilated (arterial PCO2 15-20 Torr) for 24-48 h with 100% O2 and compared with unventilated controls. Pulmonary function testing was performed, and biochemical indicators of lung injury were analyzed from tracheobronchial aspirates at 0, 24, and 48 h. Lung sections were obtained for light and electron microscopy, and bronchoalveolar lavage fluid was analyzed for surfactant composition and activity. At 24 h significant changes in tracheobronchial aspirate albumin concentrations (up 78%) and percent of polymorphonuclear cells (up 16%) were demonstrated. At 48 h a 35% decrease in dynamic lung compliance (P less than 0.05) and a 36% increase in pulmonary resistance (P less than 0.05) were noted. Further biochemical abnormalities occurred with total cell counts increased by 271% (P less than 0.02), albumin 163% (P less than 0.05), total protein 217% (P less than 0.01), and elastase 108% (P less than 0.02). Pathological analyses revealed mild lung injury at 24 h and marked inflammation, abnormal inflation patterns, flattening of Clara cells, fibrinous exudate and edema, early collagen formation, and cell necrosis observed at 48 h. Bronchoalveolar lavage surfactant had normal biophysical activity. Results demonstrate that exposure of neonatal piglets to O2 and mechanical hyperventilation for 48 h cause severe progressive lung injury.
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PMID:Lung injury in the neonatal piglet caused by hyperoxia and mechanical ventilation. 279 94

The effects of hydroxyl radical inhibition on an experimental model of normobaric pulmonary oxygen toxicity have been studied. The metal ion chelator, desferrioxamine (which inhibits hydroxyl-radical generation) or the hydroxyl-radical scavenger, dimethylthiourea (DMTU), were administered in an attempt to block hydroxyl-radical-mediated tissue injury. Lung injury was monitored in Sprague-Dawley rats by examining lung histology and bronchoalveolar lavage and by assessing pulmonary capillary permeability using the 125I-albumin lung permeability index and the lung weight:body weight ratio. Control animals had lung permeability indices 0.183 +/- 0.005 and lung weight to body weight ratio of 4.50 +/- 0.10 (all as mean +/- SEM). With increased duration of exposure to hyperoxia, there was a progressive increase in pulmonary inflammation, with thickening of alveolar membranes and atelectasis and a progressive increase in lung permeability indices (0.434 +/- 0.088 at 24 hrs; 0.954 +/- 0.165 at 48 hrs; and 1.55 +/- 0.214 at 60 hrs); and lung weight to body weight ratio (5.28 +/- 0.11 at 24 hrs; 6.54 +/- 0.23 at 48 hrs; and 8.91 +/- 0.51 at 60 hrs). Treatment with desferrioxamine provided significant protection from lung injury after 24 hrs of hyperoxia (eg., lung permeability indices 0.250 +/- 0.018; lung weight to body weight ratio 4.68 +/- 0.14, both p less than 0.025; cf. 24-hr hyperoxia controls) but no reduction in pulmonary injury was observed after 48 and 60 hrs of hyperoxia exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of normobaric pulmonary oxygen toxicity by hydroxyl radical inhibition. 282 Jun 42

Xanthine oxidase (XO)-generated toxic O2 metabolites appear to contribute to reperfusion injury, but the possibility that XO is involved in hyperoxic or neutrophil elastase-mediated injury has not been investigated. We found that lungs isolated from rats fed a tungsten-rich diet had negligible XO activities and after exposure to hyperoxia developed less acute edematous injury during perfusion with buffer or purified neutrophil elastase than XO-replete lungs from control rats which had been exposed to hyperoxia. In parallel, tungsten-treated XO-depleted cultured bovine pulmonary arterial endothelial cells made less superoxide anion and as monolayers leaked less 125I-labeled albumin after exposure to neutrophil elastase than XO-replete endothelial cell monolayers. Our findings suggest that XO-derived O2 metabolites contribute to acute edematous lung injury from hyperoxia directly and by enhancing susceptibility to neutrophil elastase.
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PMID:Xanthine oxidase mediates elastase-induced injury to isolated lungs and endothelium. 282 85

Preexposure to hypoxia increased survival and lung reduced glutathione-to-oxidized glutathione ratios (GSH/GSSG) and decreased pleural effusions in rats subsequently exposed to continuous hyperoxia. In addition, lungs from hypoxia-preexposed rats developed less acute edematous injury (decreased lung weight gains and lung lavage albumin concentrations) than lungs from normoxia-preexposed rats when isolated and perfused with hydrogen peroxide (H2O2) generated by xanthine oxidase (XO) or glucose oxidase (GO). In contrast, when perfused with elastase or exposed to a hydrostatic left atrial pressure challenge, lungs isolated from hypoxia-preexposed rats developed the same acute edematous injury as lungs from normoxia-preexposed rats. The mechanism by which hypoxia preexposure conferred protection against H2O2 appeared to depend on hexose monophosphate shunt (HMPS)-dependent increases in lung glutathione redox cycle activity. First, before perfusion with GO, lungs from hypoxia-preexposed rats had increased glutathione peroxidase and glucose 6-phosphate dehydrogenase (but not catalase or glutathione reductase) activities compared with lungs from normoxia-preexposed rats. Second, after perfusion with GO, lungs from hypoxia-preexposed rats had increased H2O2 reducing equivalents, as reflected by increased GSH/GSSG and NADPH/NADPH+, compared with lungs from normoxia-preexposed rats. Third, pretreatment of rats with an HMPS inhibitor, (6-aminonicotinamide) or a glutathione reductase inhibitor, [1,3-bis(2-chloroethyl)-1-nitrosourea] prevented hypoxia-conferred protection against H2O2-mediated acute edematous injury in isolated lungs. These findings suggest that increased detoxification of H2O2 by glutathione redox cycle and HMPS-dependent mechanisms contributes to tolerance to hyperoxia and resistance to H2O2 of lungs from hypoxia-preexposed rats.
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PMID:Hypoxia increases glutathione redox cycle and protects rat lungs against oxidants. 321 62

Hyperoxia and severe hypoxia are known to depress tracheal mucus flow in vivo. It is not clear, however, whether this is also seen in bronchial mucociliary transport system. The author attempted to ascertain acute effects of hyperoxia and moderate hypoxia on bronchial mucociliary clearance by analyzing the regional clearance of aerosolized radioactive tracers within the lung. Eleven healthy persons were exposed to pure oxygen or moderate hypoxia (mean end-tidal PaO2 57.5 mmHg) for 30 min. Twenty four patients with chronic pulmonary emphysema were studied for the chronic effect of hypoxemia on regional mucociliary clearance. They had slight hypoxemia (mean PaO2 76 mmHg). After inhalation of 99mTc-albumin aerosols, clearance of deposited aerosols was quantified as a function of time. The results were analyzed for whole right lung in the acute hyperoxic and hypoxic studies, and for 3 concentric areas representing central, mid, and peripheral regions of the right lung in the study of patients. In healthy subjects, breathing pure oxygen caused significant depression that started 30 min after the initiation of oxygen exposure and was kept up even after stopping the exposure. The clearance was significantly impaired during exposure to moderate hypoxia, though it seemed to be transient. The patients with chronic pulmonary emphysema had a significantly lower clearance in the central region than that in asymptomatic smokers (p less than 0.01). There was no significant correlation, however, between the degree of hypoxemia and the regional clearance. These results suggest that 1) acute exposure to pure oxygen and moderate hypoxia causes bronchial mucociliary dysfunction in humans, 2) the patients with chronic pulmonary emphysema have a lower clearance in the central region of the lung than asymptomatic smokers, and 3) chronic slight hypoxemia has no apparent effect on bronchial mucociliary clearance.
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PMID:[Influence of hyperoxia and hypoxia on bronchial mucociliary clearance]. 322 Apr 40

Pulmonary influxed neutrophils have been suggested to be involved in the development of hyperoxia-induced lung injury. We recently revealed that a highly toxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized by human neutrophils, thus it was named leukotoxin. Because hyperoxia-induced lung injury is a model of adult respiratory distress syndrome (ARDS), this study was designed to investigate whether or not leukotoxin is involved in the genesis of pulmonary oxygen toxicity and ARDS. After exposure to hyperoxia for 60 h, rats showed acute pulmonary edema, which was evidenced by increased lung weight, albumin concentrations, and angiotensin-converting enzyme (ACE) activities in lung lavages. These changes were correlated with an increased number of neutrophils. We detected leukotoxin in lung lavages of rats after exposure to hyperoxia for 60 h by high performance liquid chromatography and gas-chromatography/mass spectrometry. After intravenous injection of leukotoxin (100 mumol/kg) to rats, acute edematous lung injury occurred showing increases in lung weight, lung lavage albumin concentrations, and lung lavage ACE activities. In the lung lavages obtained from 5 patients with ARDS, significant increases in albumin concentrations and ACE activities were observed compared with those from subjects without pulmonary disease. Moreover, considerable amounts of leukotoxin, 38.5 +/- 21.9 nmol/lung lavage, were observed in the lavages from patients with ARDS. These findings suggest that leukotoxin plays an important role in the genesis of acute edematous lung damage in pulmonary oxygen toxicity, and that leukotoxin also links with the development of lung injury observed in patients with ARDS.
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PMID:Existence of leukotoxin 9,10-epoxy-12-octadecenoate in lung lavages from rats breathing pure oxygen and from patients with the adult respiratory distress syndrome. 334 35

When confluent calf pulmonary arterial endothelial monolayers cultured on polycarbonate micropore membranes were exposed to hyperoxia (95% O2) for 3 days, endothelial cells became enlarged, and their permeability to 125I-labeled albumin was markedly increased. Similar changes were not observed when endothelial monolayers were exposed to hyperoxia for 1 or 2 days. Cell counting and acridine orange staining of endothelial monolayers revealed that the hyperoxia-induced increase in albumin permeability was not associated with a denuding injury or loss of cells from the monolayers. Vimentin filament staining of O2-exposed monolayers showed thickening of the perinuclear vimentin coil in some cells. Rhodamine-phalloidin staining demonstrated that hyperoxia caused a progressive alteration in the actin distribution. Two days after O2 exposure, peripheral actin bands became thinner, whereas the number of cytoplasmic stress fibers was increased. Three days after O2 exposure, peripheral actin bands of most cells were disrupted or absent. Because peripheral actin bands play an important role in maintaining the integrity of endothelial monolayers, disruption of peripheral bands by hyperoxia may in part be responsible for the observed change in permeability.
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PMID:Hyperoxia causes increased albumin permeability of cultured endothelial monolayers. 336 37


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