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

Hyperoxia has been suggested as a risk factor for kernicterus. The toxicity of hyperoxia may be mediated by free radicals. We investigated the effects of free radicals, formed by the hypoxanthine/xanthine oxidase system, with and without additional hyperoxia, on the accumulation of bilirubin and albumin in rat brain. Hypoxanthine was infused for 60 min into retrograde carotid catheters in awake, young, male SPRD rats. After 30 min the infusion was briefly interrupted to inject xanthine oxidase 1 U/kg through the same catheter. Group I (controls) received 0.9% NaCl in lieu of hypoxanthine/xanthine oxidase. Groups I and II breathed room air at all times, while group III breathed 90% O2. After 60 min all groups received a bolus dose of 125I-albumin through a peripheral venous catheter, followed by bilirubin 25 mg/kg for 5 min, then bilirubin 35 mg/kg for 55 min. There were no significant differences between the groups as regards serum bilirubin, serum albumin, brain bilirubin, or brain albumin. Neither during normoxic nor hyperoxic conditions did the hypoxanthine/xanthine oxidase system increase the accumulation of bilirubin or albumin in rat brain.
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PMID:The effects of hypoxanthine, xanthine oxidase and hyperoxia on the accumulation of bilirubin and albumin in young rat brain. 149 69

To determine if prophylactic corticosteroids would prevent acute lung injury caused by hyperoxia and barotrauma, 29 piglets (1.2 +/- 0.3 kg, 1-2 days of age) were studied. Ten piglets were hyperventilated [arterial PCO2 (PaCO2) 15-20 Torr] with 100% O2 for 48 h and compared with 10 piglets treated with the identical management but given 0.7 mg/kg of dexamethasone at time 0 and every 12 h for the 48-h study. Six piglets were normally ventilated (PaCO2 40-45 Torr) for 48 h with 21% O2 as an additional control group. Pulmonary function and tracheal aspirates were examined at time 0 and every 24 h. Bronchoalveolar lavage was performed for surfactant analyses at the conclusion of the study. In animals treated with hyperoxia and hyperventilation, lung compliance decreased 32% and tracheal aspirate polymorphonuclear leukocyte (PMN) chemotactic activity increased by 51%, cell counts by 204%, number of PMNs by 277%, elastase activity by 111%, and albumin concentration by 328% over 48 h (P less than 0.05). In contrast, dexamethasone-treated piglets had increases in only tracheal aspirate albumin concentration (206%) over the 48-h study. All cellular and biochemical variables were lower in dexamethasone-treated compared with hyperoxic hyperventilated piglets. Room air normal ventilation controls had only a 108% increase in tracheal aspirate albumin concentration noted. Despite quantitative differences in surfactant among the three groups, activity was unaffected. Results indicate that hyperoxia and hyperventilation for 48 h causes significant inflammatory changes and acute lung injury and that prophylactic high-dose dexamethasone significantly ameliorates this lung damage.
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PMID:Prophylactic effects of dexamethasone in lung injury caused by hyperoxia and hyperventilation. 159 21

In order to differentiate the effects of hyperoxia and barotrauma in the pathogenesis of acute neonatal lung injury, piglets were either hyperventilated (Paco2, 15-20 torr) for 48 hours with 100% oxygen (Group I), hyperventilated with 21% oxygen (Group II), normally ventilated (Paco2, 40-45 torr) with 100% oxygen (Group III), or normally ventilated with 21% O2 (Group IV) and compared to unventilated controls. Pulmonary function was tested, and biochemical indicators of lung injury were analyzed in tracheo-bronchial aspirates at 0, 24, and 48 hours. Bronchoalveolar lavage fluid was analyzed for surfactant composition and activity at the end of the study. At 48 hours, hyperoxic, hyperventilated piglets had significantly decreased dynamic lung compliance (30%) and increased pulmonary resistance (16%), aspirate cell count (190%), elastase activity (88%), albumin (214%), and total protein (150%) concentration. Qualitative light microscopy showed moderate to severe atelectasis, fibrinous exudate, edema, and inflammation. Normoxic, hyperventilated animals had comparable changes in pulmonary mechanics, but significantly milder cellular, biochemical, and morphologic changes. In hyperoxic, normocarbic animals pulmonary physiologic, cellular, and biochemical variables changed comparably to hyperoxic, hyperventilated animals; the pathologic changes were intermediate between hyperoxic, hyperventilated and normoxic, hyperventilated piglets. Normoxic, normocarbic animals had no significant changes in most variables over 48 hours; on morphologic examination their lungs were similar to unventilated controls and showed only mild edema. Surfactant had normal biophysical activity in all animals. Our results demonstrate that hyperoxia causes more significant physiologic, inflammatory, and histologic changes than barotrauma alone. Future attempts to prevent lung injury in neonates should be directed primarily at oxygen toxicity.
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PMID:Differential effects of oxygen and barotrauma on lung injury in the neonatal piglet. 185 12

We studied the effects of hypoxia and hyperoxia on the angiogenesis process in the chick embryo chorioallantoic membrane (CAM) using four different morphometric measurements of vascularity. Chick eggs were incubated in various oxygen atmospheres (12, 16, 21, 45, or 70% oxygen) beginning on the 7th day of development, and vascularity was measured on the 14th day. Measurements of vascularity included vessel endpoint density (VED), length density, fractional image area, and a vascular density index. All measurements were made on blood vessels in randomly selected areas of CAM using a computerized image analysis system. An opaque colloidal carbon-albumin perfusate was used as a vascular marker. All four measurements showed that vascularity of CAM was inversely related to the oxygen tension to which the embryos were subjected. The VED, an estimate of total number of pre- and postcapillary vessels, exhibited the greatest degree of change, but overall changes in vascularity were modest. Prolonged exposure to a 12% oxygen atmosphere increased VED by approximately 16%, whereas 70% oxygen decreased VED by approximately 19% compared with room air control groups. We also studied the normal growth of CAM vasculature from days 8 to 18 of development. In these studies, the values of VED increased progressively throughout the entire period of development, whereas the other measurements of vascularity reached maximum values by the 14th day. We conclude that hypoxia stimulates angiogenesis in the CAM in a dose-related manner, hyperoxia inhibits CAM angiogenesis in a dose-related manner, and VED provides a sensitive estimate of vascularity in chick CAM throughout its development.
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PMID:Morphometric measurements of chorioallantoic membrane vascularity: effects of hypoxia and hyperoxia. 201 35

Reactive oxygen species are a major cause of damage occurring in ischemic tissue after reperfusion. During reperfusion transitional metals such as iron are required for reactive oxygen species to mediate their major toxic effects. Xanthine oxidase is an important source of reactive oxygen species during ischemia-reperfusion injury, but not in all organs or species. Because cytochrome P-450 enzymes are an important pulmonary source of superoxide anion (O2-.) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical (.OH) formation and propagation of lipid peroxidation, we postulated that cytochrome P-450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P-450 enzymes in a rabbit model of reperfusion lung injury. The P-450 inhibitors 8-methoxypsoralen, piperonyl butoxide, and cimetidine markedly decreased lung edema from transvascular fluid flux. Cimetidine prevented the reperfusion-related increase in lung microvascular permeability, as measured by movement of 125I-albumin from the vascular space into lung water and alveolar fluid. P-450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P-450 inhibitors did not block enhanced O2-. generation by ischemic reperfused lungs, measured by in vivo reduction of succinylated ferricytochrome c in lung perfusate, but did prevent the increase in non-protein-bound low molecular weight chelates of iron after reperfusion. Thus, cytochrome P-450 enzymes are not likely a major source of enhanced O2-. generation, but serve as an important source of iron in mediating oxidant injury to the rabbit lung during reperfusion. These results suggest an important role of cytochrome P-450 in reperfusion injury to the lung and suggest potential new therapies for the disorder.
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PMID:Role of cytochrome P-450 in reperfusion injury of the rabbit lung. 217 18

Rats were exposed to 100% oxygen for up to 60 h to determine early changes in lung permeability leading to the development of pulmonary edema. The time course of development of increased solute flux was assessed by the clearance of 99mTc-labeled diethylenetriamine pentaacetate (99mTc-DTPA) from the lung and the accumulation of 125I-labeled albumin (125I-albumin) in the lung. These end points were related to the development of pulmonary edema by the measurement of the wet-to-dry weight ratio of the lung and the weight of fluid in the pleural cavity. No significant changes occurred until 48 h of hyperoxia, when sharp increases in both indexes of lung permeability and wet-to-dry weight ratio occurred. By 60 h of exposure, pleural effusions had developed. The volume of this effusion was significantly correlated to both 99mTc-DTPA clearance and 125I-albumin flux.
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PMID:Time course of changes in lung permeability and edema in the rat exposed to 100% oxygen. 226 77

In spite of the development of various antibiotics, management of elderly patients with pneumonia remains an important problem. It is suggested that adult respiratory distress syndrome (ARDS) and disseminated intravascular coagulation (DIC) often occur in elderly patients with pneumonia. Although neutrophils are suggested to be involved in the genesis of these conditions, details remain unknown. We demonstrated that a highly cytotoxic substance, 9,10-epoxy-12-octadecenoate, is biosynthesized from linoleate by human neutrophils, thus it was named leukotoxin. Leukotoxin was detected in lung lavages from patients with ARDS. In these lung lavages, increases in albumin concentration and angiotensin converting enzyme (ACE) activity were also observed. Similar results were observed in lung lavages from rats after exposure to hyperoxia for 60 hours in an experimental model of ARDS. Intravenous administration of leukotoxin (100 mumol/kg) caused lung edema. Albumin concentration and ACE activity were increased in lung lavages of rats receiving leukotoxin. In contrast, these changes were not observed in rats administered with linoleate. Furthermore, administration of leukotoxin (100 mumol/kg) caused coagulation abnormality, i.e., increase in fibrin-fibrinogen degradation products, decrease in fibrinogen, and prolongation of activated partial thromboplastin time and prothrombin time. Administration of linoleate did not induce these changes. It is indicated that O2- was produced by respiratory burst enzyme located in neutrophil plasma membrane, and that hydroxyl radicals derived from O2- by Fenton reaction were responsible for leukotoxin synthesis. From our results, leukotoxin, a product of hydroxyl radicals and linoleate, might be responsible for the genesis of ARDS and DIC.
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PMID:[Leukotoxin and pulmonary injury]. 238 90

Since charge as well as size may influence the passage of plasma proteins from blood to lung lymph, we used uncharged dextrans as tracers to study the effects of hyperoxic lung injury on the molecular sieving properties of the pulmonary microcirculation in unanesthetized sheep. Polydisperse [3H]dextran was infused intravenously into five sheep before and after the animals breathed 100% O2 until lymph flow increased threefold (66-84 h). Lymph-to-plasma concentration ratios (L/P) were determined for [3H]dextran fractions of graded molecular sizes (1.6-8.4 nm effective radius) from samples obtained during the infusions. Before hyperoxia the blood-lymph barrier was highly restrictive to transport of [3H]dextrans above 5.0 nm in radius; steady-state L/P for these molecules averaged 0.03 or less. After the sheep breathed 100% O2, [3H]dextrans as large as 8.4 nm radius appeared in the lymph. Posthyperoxia, the L/P were significantly increased relative to prehyperoxia base-line values for every [3H]dextran fraction larger than 2.0 nm radius (P less than 0.05). In contrast, neither the L/P for albumin or total protein changed significantly. At autopsy, electron microscopy showed widespread damage to the endothelium of the alveolar capillaries with infrequent gaps between endothelial cells. In two control sheep, inhalation of compressed air for 96 h had no effect on lymph flow or L/P for the [3H]dextrans. We conclude that O2 poisoning reduced the selective sieving of uncharged dextrans across the blood-lymph barrier of the lungs and allowed larger dextrans to enter the lymph. These larger molecules may have leaked from the pulmonary microcirculation via disruptions in the continuity of the endothelial lining.
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PMID:Effect of 100% O2 on passage of uncharged dextrans from blood to lung lymph. 242 96

Pulmonary toxicity is an important adverse effect of bleomycin treatment. Very little is known of the mechanisms underlying the development of lung injury, especially after intravenous administration, or how it can be modulated. In this study acute lung injury induced by bleomycin has been examined in rats by assessment of alveolar lavage cell profiles, histological examination, and measurement of the total pulmonary extravascular albumin space. Intratracheal instillation of bleomycin 1.5 mg resulted in a severe pneumonitis with influx of inflammatory cells into the alveoli as assessed by alveolar lavage, oedema of the alveolar walls, and up to an eight fold increase in the total pulmonary extravascular albumin space, maximal at 72 hours. Intravenous bleomycin 0.15-5 mg produced no detectable injury when assessed in these ways. Exposure to hyperoxia (40-90%) after intravenous bleomycin, however, induced lung injury similar to that produced by intratracheal bleomycin. A much more severe injury followed administration of intravenous bleomycin after an exposure to hyperoxia, which itself resulted in lung injury; but lung injury was still detectable after bleomycin when the exposure to hyperoxia was insufficient to induce changes in control animals. Lung injury was not observed when the exposure to hyperoxia preceded bleomycin treatment. These results indicate the importance of oxygen in the pathways leading to acute lung injury following intravenous bleomycin. We conclude that exposure to oxygen might induce lung injury during and after bleomycin treatment, and suggest that in these circumstances oxygen therapy should be kept to a minimum.
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PMID:Development of acute lung injury after the combination of intravenous bleomycin and exposure to hyperoxia in rats. 244 92

The development of acute lung injury in rats following the intravenous injection of bleomycin was assessed by measuring the total pulmonary extravascular albumin space. Intravenous bleomycin alone produced no evidence of lung injury, yet when combined with a simultaneous exposure to hyperoxia or simultaneous tracheal instillation of ferric iron or ascorbate a severe lung injury evolved. Neither ferric iron or ascorbate alone produced lung injury when assessed in this manner, and ferrous iron, ferritin and haemoglobin did not potentiate bleomycin induced lung injury. A continuous subcutaneous infusion of desferrioxamine enhanced hyperoxia induced lung injury, and had no modulating effect on the lung injury produced by combined intravenous bleomycin and hyperoxia. These results indicate that ferric iron can potentiate bleomycin induced lung injury, and that the metal chelator desferrioxamine can have adverse effects on the development of acute lung injury.
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PMID:The effects of iron and desferrioxamine on the lung injury induced by intravenous bleomycin and hyperoxia. 246 85


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