UMLS:C0242706 - FACTA Search

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

Exposure of rats to hyperoxia or to treatment with endotoxin, increases lung manganese superoxide dismutase (MnSOD) gene expression. However, the paths by which these environmental signals are transduced into enhanced MnSOD gene expression are unknown. We now provide evidence that heterotrimeric G proteins are involved in the hyperoxia-induced increase in lung MnSOD gene expression but that pertussis toxin-sensitive G proteins are not involved in the endotoxin-induced elevation of lung MnSOD gene expression. We also show that treating rats with pertussis toxin decreased lung MnSOD activity approximately 50%. This decline in MnSOD activity occurred without a change in the lung activity of copper-zinc SOD, catalase, or glutathione peroxidase. In air-breathing rats, the pertussis toxin-induced decrease in MnSOD activity was associated with the development of lung edema, pleural effusion with a high concentration of protein, and biochemical evidence of lung oxygen toxicity. Compared to air-breathing rats, maintenance of pertussis toxin-treated rats under hypoxic or hyperoxic conditions respectively decreased or increased intrathoracic fluid. Endotoxin treatment elevated lung MnSOD activity and protected pertussis toxin-treated rats from an increase in intrathoracic fluid.
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PMID:Pertussis toxin treatment alters manganese superoxide dismutase activity in lung. Evidence for lung oxygen toxicity in air-breathing rats. 820 Sep 62

The microscopic lymphatics of the lung can be cast and studied with scanning electron microscopy. This technique shows several different forms of lymphatics and the interstitial space that leads into lymphatics as no other method can. To study changes in lymphatic forms, rats were placed in 85% oxygen for 7 days to produce pulmonary edema. Methyl methacrylate resin was injected into the lung vasculature at various times after the animals were removed from hyperoxia. In the animals not exposed to hyperoxia, no artery, vein, or airway was surrounded by a lymphatic cast. However, in rats that were in the hyperoxic chamber, 22% of arteries, 30% of veins, and 51% of indeterminate blood vessels (which could be arteries or veins) were encompassed by saccular lymphatic casts. These lymphatics were still observed 7 days after recovery from hyperoxia. Fourteen days after hyperoxia, the lymphatics returned to control values. Only 9% of the pleural surface of the animals not exposed to hyperoxia had initial lymphatics. Fifty-two percent of the hyperoxia-exposed animals had initial lymphatics, measured 3 days after exposure. This decreased to 14% 14 days after exposure to hyperoxia (P < 0.01). Conduit lymphatics were found on the pleural surfaces of 33% of animals exposed to ambient air and 100% of animals exposed to the high-oxygen environment (P < 0.05). The median percentage of the pleural surface covered with lymphatics was 0 in the animals exposed to ambient air. It was 65% in animals exposed to hyperoxia, 3 days after returning to room air. It was again 0 in animals exposed to hyperoxia, 14 days after returning to room air (P < 0.001). The lymphatics around veins expanded more than around arteries (P < 0.0001). These results indicate that in the rat all compartments of the lung lymphatics expand after the injury and edema caused by oxygen and return to normal with the resolution of the edema.
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PMID:Lung lymphatics increase after hyperoxic injury. An ultrastructural study of casts. 820 75

Active Na+ transport and lung edema clearance were studied in a model of lung injury caused by sublethal oxygen exposure. Rats exposed to 85% O2 for 7 days were studied at 0, 7, 14, and 30 days after removal from the hyperoxic chamber and compared with room air controls. In the isolated-perfused, fluid-filled rat lung, albumin flux from the perfusate into the air spaces increased after oxygen exposure and returned to control values after 7 days of recovery. However, permeability to small solutes (Na+ and mannitol) normalized only after 30 days of recovery from hyperoxia. Active Na+ transport increased immediately after oxygen exposure and returned to control values 7 days after removal from hyperoxic chamber. Na-K-adenosinetriphosphatase (ATPase) activity, and protein expression in alveolar epithelial type II cells obtained at the end of the isolated lung experiments increased significantly after the oxygen exposure compared with controls in association with the increased active Na+ transport. We conclude that active Na+ transport and lung liquid clearance are increased in the subacute hyperoxic phase of lung injury in rats, due in part to the upregulation of alveolar epithelial Na-K-ATPases. Conceivably, this behavior protects against the effects of lung injury by allowing the injured lung to clear edema more effectively. Accordingly, this upregulation may be targeted as a strategy to diminish edema in patients with lung injury.
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PMID:Active sodium transport and alveolar epithelial Na-K-ATPase increase during subacute hyperoxia in rats. 820 51

In respiratory failure, transferrin (TF) with variable iron saturation accumulates in the alveolar space. Binding free iron to TF may inhibit metal-catalyzed formation of free radicals. The aim of this study was to evaluate whether the degree of the iron-saturation of TF influences the severity of respiratory failure and surfactant responsiveness. Surfactant deficiency and lung edema was induced in 42 paralyzed and ventilated young rabbits by bronchoalveolar lavage (BAL); 19 of these animals were preexposed to 100% O2 for 40 hours. The animals received (1) exogenous surfactant intratracheally (100 mg/kg in 4 ml/kg saline); (2) surfactant and Fe(3+)-TF (50 or 25 mg/kg); or (3) surfactant and iron-free TF (50 mg/kg). One hour after administration of TF, 13-25% of exogenous TF was recovered by BAL. Administration of Iron-free TF significantly decreased the iron saturation of TF in BAL. In acute respiratory failure induced by BAL, Fe(3+)-TF decreased the efficacy of exogenous surfactant in improving the gas exchange, and increased surfactant inhibition, while iron-free TF had no effect. By contrast, in respiratory failure induced by hyperoxia and BAL, iron-free TF improved the efficacy of exogenous surfactant, but Fe(2+)-TF had no effect. After administration of iron-free TF, surfactant isolated from BAL was more surface-active than surfactant from BAL of the other hyperoxia-treated animals. In animals exposed to hyperoxia, treatment with iron-free TF decreased malondialdehyde content of BAL. We propose that low iron saturation of TF decreases oxidant stress and favors the recovery from respiratory failure.
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PMID:Transferrin modifies surfactant responsiveness in acute respiratory failure: role of iron-free transferrin as an antioxidant. 885 99

We investigated the effects of hyperoxia on the activities of hepatic ethoxyresorufin O-deethylase (EROD) (CYP1A1), methoxyresorufin O-demethylase (MROD) (CYP1A2), and glutathione transferase-alpha (GST-alpha), and the status of protein thiols (PSH) in male Sprague-Dawley rats. Twenty-four h of hyperoxia more than doubled EROD and MROD activities, which were increased 7.6- and 3.3-fold, respectively, after 48 h of hyperoxia. The increases in EROD and MROD activities were paralleled by enhanced CYP1A1/1A2 apoproteins contents, as detected by Western analysis. At 60 h of hyperoxia, by which time hyperoxic Sprague-Dawley rats display marked respiratory distress, pulmonary edema, and other markers of pulmonary dysfunction, the activities and levels of hepatic CYP1A1 and 1A2 had declined dramatically and returned to levels observed in air-breathing control animals. Hepatic activities of GST-alpha, as well as PSH status, were not altered significantly in the hyperoxic animals at any time point. The marked induction and subsequent decline of hepatic CYP1A1/1A2 activities in rats exposed to hyperoxia suggest that these enzymes may contribute to the mechanisms of injury and/or to adaptive responses to hyperoxic exposures in vivo.
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PMID:Induction and decline of hepatic cytochromes P4501A1 and 1A2 in rats exposed to hyperoxia are not paralleled by changes in glutathione S-transferase-alpha. 902 Apr 4

We investigated effects of acute hyperoxia on solute transport from air space to vascular space in isolated rat lungs. Air spaces were filled with Krebs-Ringer bicarbonate solution containing fluorescein isothiocyanate-labeled dextran (FD-20; mol wt 20,000) and either 22Na+ and [14C]sucrose, or D-[14C]glucose and L-[3H]glucose. Apparent permeability-surface area products for tracers over time (up to 120 min) were calculated for isolated perfused lungs from control rats (room air) and rats exposed to > 95% O2 for 48 or 60 h immediately postexposure. After O2 exposures, mean fluxes for [14C]sucrose and FD-20 were significantly higher than in room-air control lungs. However, amiloride-sensitive Na+ and active D-glucose fluxes were unchanged after hyperoxic exposure. Therefore, it is unlikely that decreases in net solute transport in this lung-injury model contributed to pulmonary edema resulting from O2 toxicity. Increased net solute transport shown to help resolve pulmonary edema after acute hyperoxic exposure must therefore begin during the recovery period. In summary, our data show increases in passive solute fluxes but no changes in active solute fluxes immediately after acute hyperoxic lung injury.
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PMID:Effects of acute hyperoxic exposure on solute fluxes across the blood-gas barrier in rat lungs. 902 22

Alveolar fluid is resorbed using active Na+ transport primarily through basolateral sodium-potassium-adenosinetriphosphatase (Na-K-ATPase) and apical Na+ channels that are particularly dense on the alveolar type II (ATII) epithelial cells. During lung injury with pulmonary edema, continued or accelerated Na+ and fluid resorption is critical for a favorable outcome. However, little is known of how ATII cell Na+ transport is affected during injury. These experiments examined the effects of acute lung injury on ATII cell Na-K-ATPase activity and expression using an established model of rats exposed to 100% O(2) for 60 h. Na-K-ATPase activity of ATII cells isolated immediately after exposure was assessed by ouabain-sensitive (86)Rb+ uptake in intact cells and by ouabain-sensitive P(i) production by cell membranes. In the presence of 1 mM ouabain, ouabain-sensitive Rb+ uptake was not different between normoxic and hyperoxic cells, but the apparent Na-K-ATPase maximal velocity (Vmax) of hyperoxic cell membranes was 75 +/- 8% of normoxic membranes (P < 0.05). On Western blots of ATII cell membranes, alpha1-subunit protein significantly decreased with hyperoxia (35 +/- 9% of normoxia; P < 0.05), whereas the amounts of the beta-subunit were unchanged (P > 0.05). On Northern blots of ATII cell total RNA, steady-state levels of both the alpha1- and beta1-subunit mRNA increased after hyperoxia (alpha1 = 2.5 +/- 1.3-fold; beta1 = 4.6 +/- 2.5-fold). Thus despite hyperoxic decreases in Na-K-ATPase Vmax and the amount of alpha1-protein, Rb+ uptake by Na-K-ATPase in intact cells was unchanged. The mRNA levels, protein amounts, and enzyme activity did not respond in parallel to hyperoxic injury, and the activity in intact cells correlated best with the amounts of the beta-subunit, the limiting component in de novo pump assembly in many tissues.
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PMID:Effects of hyperoxia on type II cell Na-K-ATPase function and expression. 912 12

Prolonged hyperoxia causes lung injury and respiratory failure secondary to oxidative tissue damage mediated, in part, by the superoxide anion. We hypothesized that aerosol treatment with recombinant human manganese superoxide dismutase (rhMnSOD) would attenuate hyperoxic lung damage in primates. Adult baboons were anesthetized and ventilated with 100% oxygen for 96 h or until death. Six animals were treated with aerosolized rhMnSOD (3 mg . kg-1 . day-1 in divided doses), and six control animals did not receive enzyme therapy. Physiological variables were recorded every 12 h, and ventilation-perfusion ratio relationships were evaluated by using the multiple inert-gas elimination technique. After the experiments, surfactant composition and lung edema were measured. We found that rhMnSOD significantly decreased pulmonary shunt fraction (P < 0.01) and preserved arterial oxygenation (P < 0.01) during hyperoxia. The rhMnSOD increased lung phospholipids, phosphatidylcholine and disaturated phosphatidylcholine, and decreased lung edema in this model. Testing of higher and lower doses of MnSOD (1 and 10 mg . kg-1 . day-1) in two other groups of baboons produced variable physiological protection, suggesting a "window" of effective dosage. We conclude that aerosolized MnSOD (3 mg . kg-1 . day-1) affords significant preservation of pulmonary gas exchange during hyperoxic lung injury.
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PMID:Aerosolized manganese SOD decreases hyperoxic pulmonary injury in primates. I. Physiology and biochemistry. 926 52

Clara cell secretory protein (CCSP) is an abundant component of the extracellular lining fluid of airways. Even though the in vivo function of CCSP is unknown, in vitro studies support a potential role of CCSP in the control of inflammatory responses. CCSP-deficient mice (CCSP -/-) were generated to investigate the in vivo function of this protein (13). In this study, we used hyperoxia exposure as a model to investigate phenotypic consequences of CCSP deficiency following acute lung injury. The pathologic response of the mouse lung to hyperoxia, and recovery of the lung, include inflammatory cell infiltrate and edema. Continuous exposure to > 95% O2 was associated with significantly reduced survival time among CCSP -/- mice as compared with strain-, age-, and sex-matched wild-type control mice. Differences in survival were associated with early onset of lung edema in CCSP -/- mice as compared with wild-type controls. To further investigate these differences in response, mice were exposed to > 95% O2 for either 48 h or 68 h with one group receiving 68 h of hyperoxia followed by room-air recovery. Lung RNA was characterized for changes in the abundance of cytokine messenger RNA (mRNA) using a ribonuclease (RNase) protection assay. After 68 h of hyperoxia, interleukin-6 (IL-6), IL-1beta, and IL-3 mRNAs were 14-, 3-, and 2.5-fold higher, respectively, in CCSP -/- mice than in similarly exposed wild-type control mice. Increased expression of IL-1beta mRNA in hyperoxia-exposed CCSP -/- mice was localized principally within the lung parenchyma, suggesting that the effects of CCSP deficiency were not confined to the airway epithelium. We conclude that CCSP deficiency results in increased sensitivity to hyperoxia-induced lung injury as measured by increased mortality, early onset of lung edema, and induction of proinflammatory cytokine mRNAs.
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PMID:Altered pulmonary response to hyperoxia in Clara cell secretory protein deficient mice. 927 2

Active Na+ transport by the alveolar epithelium keeps alveoli relatively dry. Hyperoxia increases epithelial permeability, resulting in pulmonary edema. We sought to determine whether active Na+ resorption from the air spaces and Na-K-ATPase activity increased in rats exposed to > 95% O2 for 60 h. The permeability x surface area products for unidirectional resorption of alveolar [14C]sucrose (PSsucrose) and 22Na+ (PSNa+) were measured in isolated, perfused rat lungs immediately after hyperoxia and after 3 and 7 days of recovery in room air. At 60 h of hyperoxia, the mean PSsucrose and PSNa+ increased from 6.71 +/- 0.8 x 10(-5) to 12.6 +/- 1.6 x 10(-5) cm3/s (P = 0.029) and from 23.6 +/- 1.1 x 10(-5) to 31.0 +/- 1.6 x 10(-5) cm3/s (P < 0.008), respectively. However, the values in individual rats ranged widely from no change to nearly a fourfold increase. Subgroup analysis revealed that benzamil- or amiloride-sensitive (transcellular) PSNa+ was significantly reduced in the exposed lungs with normal PSsucrose but was maintained in the lungs with high PSsucrose. By day 3 of recovery, mean Na+ and sucrose fluxes returned to values similar to control. Na-K-ATPase membrane hydrolytic maximal velocity (Vmax) activity fell significantly immediately after hyperoxic exposure but recovered to normal values by day 3 of recovery. The Na-K-ATPase beta 1-subunit antigenic signal did not significantly change, whereas the alpha 1-subunit levels increased during recovery. In summary, there was a heterogeneous response of different rats to acute hyperoxia. Hyperoxia led to complex, nonparallel changes in Na+ pump antigenic protein, hydrolytic activity, and unidirectional active Na+ resorption. Active Na+ transport was differentially affected, depending on degree of injury, but permeability and transport normalized by day 3 of recovery.
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PMID:Hyperoxic effects on alveolar sodium resorption and lung Na-K-ATPase. 943 74

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