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

Lung structure and function, and the effect of surfactant replacement, were studied in three animal models of adult respiratory distress syndrome (ARDS): surfactant depletion by repeated lung lavage, proteinaceous pulmonary edema induced by prolonged exposure to hyperoxia, and inoculation with hybridoma making an antibody to the hydrophobic surfactant-associated protein, SP-B. Surfactant replacement therapy restored normal gas exchange in respiratory failure induced by repeated lung lavage but was ineffective in animals with severe lung parenchymal lesions induced by hyperoxia or antibody to SP-B. Lung edema fluid from animals exposed to hyperoxia inhibited surfactant function in a concentration-dependent manner. These observations indicate that, in experimental ARDS, the effect of surfactant replacement depends on the type of animal model and, especially, on the degree of lung injury present at the time of therapy.
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PMID:Surfactant inactivation and surfactant replacement in experimental models of ARDS. 192 24

We have recently shown that exposure of Chinese hamster ovary (CHO) cells to a toxic dose of normobaric hyperoxia (98% O2 for 3 days) caused a disturbance of cellular energy metabolism, that is, respiratory failure followed by stimulation of glycolytic activity and a net depletion of ATP. Respiratory failure was correlated with a selective inactivation of three mitochondrial enzymes, that is, partial inactivation of NADH dehydrogenase and virtually complete inactivation of succinate and alpha-ketoglutarate dehydrogenase activities (Schoonen et al., 1990). To elucidate the biochemical basis of resistance to hyperoxia in a previously described oxygen-resistant substrain of Chinese hamster ovary (CHO) cells, we compared the resistant cells with wildtype CHO cells with respect to several key parameters of oxidative and glycolytic energy metabolism. The two cell types were critically different in that the succinate and alpha-ketoglutarate dehydrogenases of the oxygen-resistant cells were relatively resistant to inactivation by hyperoxia, which may at least partly explain their enhanced capacity to respire and survive under hyperoxic conditions. Although the biochemical basis for the observed enzyme resistance to hyperoxic inactivation remains to be elucidated, the present data underscore the importance of succinate and alpha-ketoglutarate dehydrogenases as critical targets in hyperoxic killing of wildtype CHO cells.
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PMID:Characterization of oxygen-resistant Chinese hamster ovary cells. III. Relative resistance of succinate and alpha-ketoglutarate dehydrogenases to hyperoxic inactivation. 201 73

Cellular intoxication by elevated concentrations of O2 may be considered as a model for accelerated cellular aging processes resulting from excessive free radical production by normal metabolic pathways. We describe here that exposure of HeLa cell cultures to 80% O2 for 2 days causes progressive growth inhibition and loss of reproductive capacity. This intoxication was correlated with inhibition of cellular O2 consumption and inactivation of 3 mitochondrial flavoproteins, i.e., partial inactivation of NADH and succinate dehydrogenases and total inactivation of alpha-ketoglutarate dehydrogenase. As alpha-ketoglutarate dehydrogenase controls the influx of glutamine/glutamate into the Krebs cycle, which is the major pathway for oxidative ATP generation in HeLa cells, the inactivation of alpha-ketoglutarate dehydrogenase was expectedly correlated with a net fall in glutamine/glutamate utilization. Furthermore, a simultaneous increase in glucose consumption and lactate production was observed, indicating that the cellular response to respiratory failure is to generate more ATP from glycolysis. In spite of this response, extensive depletion of ATP was observed. Thus, hyperoxia-induced growth inhibition and loss of clonogenicity seem to be due primarily to an impairment of mitochondrial energy metabolism resulting from inactivation of SH-group-containing flavoprotein enzymes localized at or near the inner mitochondrial membrane. These observations may be relevant for theories implicating loss of mitochondrial function as a prime factor in the aging process.
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PMID:Hyperoxia-induced clonogenic killing of HeLa cells associated with respiratory failure and selective inactivation of Krebs cycle enzymes. 223 21

Continuous exposure of Chinese hamster ovary (CHO) cells to an atmosphere of 98% O2, 2% CO2 (normobaric hyperoxia) leads within a period of several days to cytostasis and clonogenic cell death. Here we report respiratory failure as an important early symptom of oxygen intoxication in CHO cells, resulting in a more than 80% inhibition of oxygen consumption within 3 days of hyperoxic exposure. This inhibition appeared to be correlated with selective inactivation of three mitochondrial key enzymes, NADH dehydrogenase, succinate dehydrogenase, and alpha-ketoglutarate dehydrogenase. The latter enzyme controls the influx of glutamate into the Krebs cycle and is particularly critical for oxidative ATP generation in most cultured cells, which depends on exogenous glutamine rather than glucose as a carbon source. As expected, the inactivation of alpha-ketoglutarate dehydrogenase was correlated with a fall in cellular glutamine utilization, which became apparent from the first day of hyperoxic exposure. Thereafter, glucose utilization and lactate excretion started to increase, up to 3-fold, indicating a cellular response to respiratory failure aimed at increased ATP generation from glycolysis. However, in spite of this response, the cellular ATP level progressively decreased, up to 2.5-fold. Thus, killing of CHO cells by normobaric hyperoxia seems to be due to a severe disturbance of mitochondrial metabolism eventually leading to a depletion of cellular ATP pools.
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PMID:Respiratory failure and stimulation of glycolysis in Chinese hamster ovary cells exposed to normobaric hyperoxia. 235 58

When tracheal intubation is conducted with traditional laryngoscope PtcO2 fall during the first minute after intubation; when continuous O2 supplied laryngoscope (Laryng O2) is used PtcO2 rise; the difference is statistically significant (p less than 0.001) either the subjects are in curarisation apnea or in spontaneous ventilation. With traditional laryngoscope, the fall is faster with spontaneous ventilation conditions than during curarisation apnea. Likewise in normal conscient subject the same fall is faster (p less than 0.001) during first minute of posthyperoxic spontaneous quiet ventilation than the first minute of voluntary hypocapnic apnea induced by hyperventilation during the same hyperoxia. Such results have to be taken into account for the indications of tracheal intubation technical means if hypoxic conditions are to be suspected, particularly for infants and subjects with cardio-respiratory failure.
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PMID:[Preliminary study of transcutaneous oxygen partial pressure in adults after discontinuing normobaric hyperoxia during intubation]. 262 5

Diffuse alveolar damage (DAD) is usually considered a generalized lung process. During five years the authors observed 83 patients with generalized DAD in 827 adult autopsies (10.1%) and 10 patients with identical, but localized, lesions. The authors propose the term regional alveolar damage (RAD) to designate localized "DAD." RAD was unilateral in six patients and most frequently involved the upper lobe. All ten patients had chronic systemic diseases and presented with life-threatening illnesses. The probable causes of RAD were multifactorial and included hypotensive shock, septicemia, pneumonia, hyperoxia, and pancreatitis. All patients developed respiratory failure, requiring supplemental oxygen and, in nine patients, mechanical ventilation. Chest roentgenograms revealed alveolar or combined alveolar and interstitial infiltrates that corresponded to the lesions found at autopsy. The reasons for localization of RAD within the lung are unclear, but the presence of proliferative lesions and frequent involvement of the upper lobe suggests that RAD is not simply an early phase of DAD and implicates additional pathogenetic factors.
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PMID:Regional alveolar damage (RAD). A localized counterpart of diffuse alveolar damage. 266 70

We recently reported that endotoxin infusion before O2 exposure significantly reduced or delayed the onset of pulmonary edema formation and respiratory failure by reducing the oxidant stress of O2 exposure. Despite these beneficial effects of endotoxin treatment, lung microvascular permeability eventually increased, but postmortem lung water content was less than expected. Prolonged O2 breathing blunts or abolishes the pulmonary constrictor response to alveolar hypoxia in some species, and it is possible that the loss of this response could contribute further to edema formation. To determine whether the reduction in lung edema observed in endotoxin-treated, O2-exposed lambs was linked to the preservation of hypoxic pulmonary vasoconstriction (HPV), we measured pulmonary vascular resistance before and after 8 min of isocarbic hypoxia (inspired O2 fraction 0.12) during each day of O2 exposure. In six control lambs, the pressor response to hypoxia was abolished after 72 h in O2, and the lambs developed respiratory failure shortly thereafter. In six endotoxin-treated lambs, HPV was preserved for as long as 144 h of O2 exposure. In two control O2-exposed lambs in whom HPV was abolished, the infusion of either angiotensin or prostaglandin H2 analogue increased pulmonary vascular resistance by greater than 75%. We conclude that in lambs 1) hyperoxia abolishes the pulmonary vascular response to hypoxia, 2) endotoxin pretreatment reduces acute O2-induced lung injury and preserves the pulmonary constrictor response to hypoxia, and 3) the loss of HPV during O2 exposure may be the result of oxidant-mediated injury to the hypoxia response itself and not the result of diffuse damage to the vasoconstrictor effector mechanism.
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PMID:Effect of endotoxin pretreatment on the pulmonary vascular response to hypoxia in O2-exposed lambs. 305 85

Adult guinea pigs were exposed to 100% oxygen until, after 54-85 h, they developed severe respiratory insufficiency. One subgroup of animals was ventilated artificially with 100% oxygen for an additional 60-960 min. When the PaO2 was less than 15 kPa or the PaCO2 greater than 20 kPa, 1 ml of porcine surfactant (phospholipid concentration 80 mg.ml-1) was instilled via the trachea. These animals were ventilated for one more hour and then sacrificed. Surfactant instillation did not improve the blood gases, nor the pulmonary pressure-volume characteristics. All hyperoxia-exposed guinea pigs showed prominent histologic lung lesions, including intraalveolar edema and desquamation of airway epithelium. Compared to normal guinea pigs the volume density of intraalveolar "gas" was decreased and that of intraalveolar fluid increased. The alveolar expansion pattern in histologic sections was not improved in the surfactant-treated animals, compared to hyperoxia-exposed guinea pigs studied immediately after death. In hyperoxia-exposed animals, about 1.5 ml of edema fluid was sampled from the airways. Evaluated with pulsating bubble, our surfactant preparation had a minimum surface tension (gamma min) close to zero. However, the gamma min values of edema fluid from surfactant-treated and nontreated guinea pigs were both about 20 mN.m-1. the edema fluid thus seemed to inhibit the essential physical properties of exogenous surfactant. This, together with the prominent lung lesions, may explain the failure of surfactant replacement therapy at a late stage of hyperoxia-induced respiratory failure.
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PMID:Inactivation of exogenous surfactant in experimental respiratory failure induced by hyperoxia. 321 91

We did two studies to see if severe neutropenia might reduce the severity or delay development of O2-induced lung microvascular injury. First, we treated 11 rabbits with nitrogen mustard until their circulating neurophil count decreased to less than 50/microliters of blood, after which the rabbits breathed pure O2 until death; nine other rabbits received no nitrogen mustard and had normal numbers of circulating neutrophils during O2 breathing. All rabbits died of respiratory failure with pulmonary edema, and although chemotherapy decreased the number of neutrophils in the lungs by greater than 90%, it did not influence survival time or extravascular lung water content. To see if severe neutropenia might slow the development of O2-induced lung microvascular injury, we assessed the effects of sustained hyperoxia on lung fluid balance in unanesthetized lambs treated with hydroxyurea, so that their absolute neutrophil count was less than 50/microliters of blood. We measured pulmonary arterial and left atrial pressures, cardiac output, lung lymph flow, and concentrations of protein in lymph and plasma during a 2- to 4-h control period and then daily for 2 to 4 h as the lambs continuously breathed pure O2. After 3 days of hyperoxia, lymph flow doubled and the concentration of protein in lymph increased from 3.3 +/- 0.5 to 4.2 +/- 0.3 g/dl. Tracer studies with 125I-albumin before and 3 days after the start of O2 breathing confirmed the development of increased lung vascular permeability to protein. All lambs died of respiratory failure with pulmonary edema after 3-5 days in O2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oxygen-induced lung microvascular injury in neutropenic rabbits and lambs. 398 Mar 93

Several reports have suggested that patients treated with bleomycin may be at greater risk of developing respiratory failure when exposed to elevated concentrations of oxygen. We studied the interactions of bleomycin and hyperoxia in Syrian golden hamsters. Animals were instilled intratracheally with bleomycin at a dose of 0.5 unit/100 g of body weight, followed immediately by exposure to 70% oxygen for 72 hours. Mortality was 90% in these hamsters, compared to 15% in an age-matched control group treated with bleomycin alone. Postmortem studies revealed that pathologic changes were confined to the lungs which showed severe, hemorrhagic, diffuse alveolar damage. To determine the effect of delaying exposure to hyperoxia, bleomycin at a dose of 0.5 unit/100 g of body weight was instilled and animals were kept in room air for 1 and 2 months before exposure to 70% or 100% oxygen for 72 hours. No significant increase in mortality or interstitial pneumonitis and fibrosis was seen in these groups during or after the hyperoxic exposures. Mortality in controls treated with saline and hyperoxia was zero. We conclude that simultaneous treatment with bleomycin and hyperoxia results in a synergistic effect on mortality and on the development of pulmonary fibrosis. However, there is no synergism if the hyperoxic exposure is delayed for at least 1 month following bleomycin treatment.
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PMID:Differences in effects of immediate and delayed hyperoxia exposure on bleomycin-induced pulmonary injury. 620 6


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