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

Emphysema in humans takes several different forms: centrilobular, panacinar, paraseptal, and airspace enlargement with fibrosis. The varying morphologic and background features of these forms of emphysema suggest that they differ in pathogenesis. Elastic fiber rupture and fraying are a feature of emphysema. Experimental emphysema may be induced by human neutrophil elastase and other elastolytic enzymes but not by nonelastolytic proteases. Disruption of elastic fibers also appears to be the underlying feature of lathyrogen-induced airspace enlargement and of the emphysema in the blotchy mouse. However, there is no evidence of elastic fiber destruction in cadmium-induced airspace enlargement with fibrosis or in emphysema associated with hyperoxia or severe starvation. Thus, elastic fiber disruption is not common to all forms of experimental emphysema. We posit that airspace enlargement may be a stereotyped response of the lungs to different injuries. Emphysema can be induced in experimental animals by repeated induction of pulmonary neutrophilia. However, the evidence for involvement of neutrophil elastase in human emphysema is not clear: there are studies using a variety of approaches that weigh on both sides of the question. There is also in vitro evidence that alveolar macrophages can degrade elastin or elastic fibers with which they are in contact by means of a metalloelastase or the cooperative action of plasminogen activator and an acid cysteine protease. We conclude that the pathogenesis of emphysema is complex. Neutrophil elastase likely plays a major role in the development of some forms of emphysema, but our understanding of the interactions between the alveolar walls and neutrophils is still fragmentary.
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PMID:Putative role of neutrophil elastase in the pathogenesis of emphysema. 206 48

Hyperoxia is routinely administered to patients with severe emphysema. To gain insight into the possibly adverse effects of such treatment, hamsters were exposed to 60% oxygen for 5 days, beginning 48 h after induction of pulmonary emphysema by intratracheal instillment of pancreatic elastase. Control groups consisted of (1) animals instilled with elastase and exposed to room air, (2) animals instilled with saline and exposed to 60% oxygen, and (3) animals instilled with saline and exposed to room air. Cross-linked elastin content and synthesis in the lung were measured immediately following termination of hyperoxia, and the mean linear intercept was determined 4 wk later. Cytologic examination of bronchoalveolar lavage fluids was also performed. Statistical significance was determined by a two-way analysis of variance. Results indicate that exposure to 60% oxygen significantly affected (p less than 0.05) air-space size, causing a 51% increase among elastase-treated hamsters (124 versus 82 microns) but only a 4% increment among saline-treated animals (52 versus 50 microns). When compared to other groups, animals treated with both elastase and hyperoxia had a significantly greater (p less than 0.01) percentage of neutrophils (28%) in their lung lavage fluids immediately following exposure to 60% oxygen. Although total lung elastin content was not altered by hyperoxia at this time, labelling of elastin cross-links was significantly increased (p less than 0.05). These studies demonstrate that exposure to 60% oxygen enhances elastase-induced lung injury. They also raise the possibility that oxygen therapy may, under certain circumstances, accelerate the progression of human emphysema.
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PMID:The effect of 60% oxygen on air-space enlargement and cross-linked elastin synthesis in hamsters with elastase-induced emphysema. 211 71

Oxidants from cigarette smoke or those produced by phagocytes are implicated in the pathogenesis of emphysema. We reasoned that augmentation of antioxidant enzymes in cigarette smokers may be important in restricting direct and indirect oxidant damage to alveolar structures. Accordingly, we studied the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSHPx), in alveolar macrophages (AM) from cigarette smokers and from smoke-exposed hamsters. The activities of these antioxidant enzymes were compared with the activities found in AM from nonsmoking control subjects. The activities of SOD and CAT from AM of smokers and smoke-exposed hamsters were twice that found in control subjects (p less than 0.01), but there was no change in the activity of GSHPx. Using the hamster model, we found that filtration of smoke attenuated the increase in antioxidant activities, and that after smoking cessation, the increased activities had returned to those found with control subjects. An adaptive response was further suggested by prolonged survival of smoke-exposed hamsters in normobaric hyperoxia (O2 greater than 95%). Chronic smoke exposure in humans or hamsters causes increased SOD and CAT activities in AM. This augmented activity may serve as a mechanism to limit oxidant-mediated damage to alveolar structures.
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PMID:Selective increase of antioxidant enzyme activity in the alveolar macrophages from cigarette smokers and smoke-exposed hamsters. 231 98

Exposure of animals to oxidant gases produces a mild emphysema, and O2-derived free radicals are capable of degrading connective tissues in vitro. It is postulated that degradation of connective tissue by O2-derived free radicals leads to emphysema in these models. To determine whether exposure of lung tissue slices to an oxidant gas results in degradation of collagen and to investigate factors mediating this degradation, we exposed lung tissue slices from normal rats to hyperoxia (95% O2, 5% CO2) and measured hydroxyproline release into the medium. After a 4-h exposure, the hydroxyproline released was 5.3 +/- 0.2 micrograms/g lung tissue (n = 10) in normoxia and 8.1 +/- 0.6 micrograms/g tissue (n = 13) in hyperoxia (p less than 0.05), suggesting degradation of collagen. The addition of 0.1% trypsin to the initial incubation medium caused a synergistic increase in hydroxyproline release from O2-exposed slices: normoxia/trypsin, 46.2 +/- 3.6 micrograms/g tissue (n = 10); hyperoxia/trypsin, 61.4 +/- 3.6 micrograms/g tissue (n = 11) (p less than 0.05). The addition of proteinase inhibitors completely suppressed the O2-induced release of hydroxyproline, suggesting that proteolytic enzymes are involved in hyperoxia-mediated degradation of lung collagen.
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PMID:Degradation of collagen in lung tissue slices exposed to hyperoxia. 303 77

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

We studied damage and repair of lung connective tissue in rats exposed to toxic amounts of oxygen by measuring lung content of collagen and elastin and the number of collagen fragments in lung lavage fluid after exposure to 98% O2 for 60 h. Lung collagen was decreased 17%, and collagen fragments in lavage fluid were increased 4- to 5-fold in O2-exposed rats compared with those in control rats. No biochemical evidence of elastin degradation was found. Mild emphysematous changes and a leftward shift of fluid-filled, pressure-volume curves were induced within 2 wk after recovery from exposure to O2. Administration of the lathyrogen beta-aminopropionitrile worsened the emphysematous lesion produced by hyperoxia, suggesting that replacement of connective tissue during repair limits the extent of emphysema. We conclude that lung collagen is degraded and an emphysematous lesion is produced by relatively short exposure to toxic amounts of oxygen.
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PMID:Damage and repair of lung connective tissue in rats exposed to toxic levels of oxygen. 381 7

Alveolo-arterial difference in PO2 (AaDO2) during moderate hyperoxia (FIO2 = 0.40) and shunt-effect (Qs/Qt) were measured in 219 patients with chronic lung disease of various aetiologies. In particular, the series included 79 chronic bronchitics, 35 cases of "primary" emphysema, 40 cases of sarcoidosis and 36 cases of diffuse interstitial pulmonary fibrosis ( DIPF ). Alveolar PO2 was calculated from the equation of alveolar air. Ventilatory parameters were measured under stable conditions using a Fleisch metabograph . Shunt-effect (in moderate hyperoxia) was calculated from the classical equation. AaDO2 in chronic bronchitis was on average 118.3 +/- 30.7 mmHg, significantly higher (p less than 0.005) than in the emphysema patients: 99.2 +/- 22.3 mmHg. The same difference between the two groups was found for shunt-effect (p less than 0.005). In sarcoidosis, AaDO2 and Qs/Qt were only slightly raised on average: 83.6 +/- 22.0 mmHg and 7.2 +/- 3.7% respectively. By contrast, in DIPF , AaDO2 was very high (124.9 +/- 35.7 mmHg) as was Qs/Qt (14.8 +/- 6.9%). The measurement (in moderate hyperoxia) of AaDO2 and Qs/Qt, which are fairly representative of ventilation-perfusion inequalities, may thus make a contribution to the physiopathological differentiation between chronic bronchitis and emphysema. The frank increase in AaDO2 and Qs/Qt in DIPF emphasises the importance of ventilation-perfusion inequalities in the development of hypoxaemia in such patients. For all the cases studied, there was a very satisfactory correlation between AaDO2 in moderate hyperoxia and PaO2 at rest in ordinary air (r = -0.64, p less than 0.001). Similarly, there was a satisfactory correlation between Qs/Qt in moderate hyperoxia and PaO2 at rest in ordinary air (r = -0.53, p less than 0.01).
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PMID:[Value of the measurement of the alveolo-arterial PO2 difference in moderate hyperoxia (FIO2 = 0.40) in chronic respiratory insufficiency]. 672 46

In order to determine if lungs with emphysema respond to oxygen toxicity in a different way from normal lungs, the effects of hyperoxia on pulmonary function, morphologic aspects, and survival were studied in rats with enzyme-induced emphysema. A hyperoxic pulmonary syndrome similar to adult respiratory distress syndrome (ARDS) was produced by a continuous 48-h exposure to 100% oxygen at 1 atm. An emphysematous condition was induced by intratracheal instillation of porcine pancreatic elastase. The 4 study groups consisted of (1) control, (2) oxygen-treated, (3) elastase-treated, and (4) combined oxygen-elastase-treated rats. The emphysematous rats exposed to 100% O2 had reductions in quasi-static compliance and CO diffusing capacity similar to those in oxygen-treated normal animals. They also had reductions in forced expiratory volumes and flow rates similar to those in rats treated with elastase alone. Histologically, there was no enhancement or attenuation of emphysematous or ARDS lesions in the combined oxygen-elastase lungs compared with that in lungs treated with only one agent. Emphysematous and normal rats were also exposed for 96 h to a similar hyperoxic atmosphere to evaluate survival. The survival curves for these 2 groups were not statistically different. These results indicate that the severity of ARDS alterations was not affected by the emphysematous condition, and hyperoxia did not enhance or attentuate preexisting emphysematous lesions. These findings suggest that emphysematous lungs respond to hyperoxia in a similar fashion to normal lungs, and that the functional and structural manifestations of oxygen toxicity are simply superimposed over preexisting emphysematous changes.
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PMID:The effects of emphysema on oxygen toxicity in rats. 718 Dec 25

Fibulin-5, previously known as DANCE and EVEC, is a secreted extracellular matrix protein that functions as a scaffold for elastin fiber assembly and as a ligand for integrins alphavbeta3, alphavbeta5, and alpha9beta1. Fibulin-5 is developmentally regulated in the lung, and lung air space enlargement develops in mice deficient in fibulin-5. Fibulin-5 is also induced in adult lung following lung injury by hyperoxia. To further examine the role of fibulin-5 during repair of lung injury, we assessed fibulin-5 expression during elastase-induced emphysema in C57/b mice. Mice were treated with either saline or elastase via the trachea, and the lung was examined 20 days after treatment. Fibulin-5 mRNA was induced almost fourfold, whereas elastin mRNA was minimally elevated. Immunohistochemistry studies showed that fibulin-5 was induced in cells within the alveolar wall following elastase treatment. Western analysis demonstrates that fibulin-5 was strongly expressed in isolated primary lung interstitial fibroblasts. Fibulin-5 protein was localized to the fibroblast cell layer in culture, and brief elastase treatment degraded the protein. Intact fibulin-5 did not accumulate in the culture media. Treatment of fibroblasts with the proinflammatory cytokine interleukin-1beta abolished fibulin-5 mRNA expression. Our results indicate that fibulin-5 is coordinately expressed and regulated with elastin in lung fibroblasts and may serve a key role during lung injury and repair.
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PMID:Coordinate expression of fibulin-5/DANCE and elastin during lung injury repair. 1290 85

Pulmonary surfactant, a complex of lipids and proteins, maintains alveolar integrity and participates in the control of host defense and inflammation in the lung. Surfactant proteins A, B, C, and D are important components of surfactant that play diverse roles in the surface tension reducing as well as host defense and inflammation control functions of surfactant. Hyperoxia or exposure of cells/tissues to elevated levels of oxygen occurs when high levels of oxygen are used to treat a variety of pulmonary disorders that include respiratory distress syndrome of premature infants, emphysema, sarcoidosis, end-stage lung diseases, and others. The lung serves as a primary target organ in hyperoxia, and hyperoxic lung injury is characterized by pulmonary edema, inflammation, and respiratory failure. Hyperoxic lung injury is associated with significant changes in the expression of surfactant proteins that likely serves as an adaptive response to elevated oxygen levels. In most animal species studied, hyperoxia increases the tissue expression of surfactant protein mRNAs. A limited number of studies have indicated that the increased tissue expression of surfactant protein mRNAs is associated with increased levels of surfactant proteins in the bronchoalveolar lavage.
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PMID:Regulation of surfactant protein gene expression by hyperoxia in the lung. 1471 50


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