Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In 1979, the appearance of the periventricular leukomalacia complex (PLC) was reported in a relatively high percent of infants coming to autopsy from our neonatal intensive care unit. Because infants with PLC had had longer periods of high P02 than did those without PLC, it was concluded that PLC was related to hyperoxia. However, in a second study it was found that the periods of hyperoxia corresponded to periods of hypotension. Therefore, the complete autopsies of 16 randomly selected newborn subjects with PLC and 21 without PLC were reviewed with particular reference to the incidence of bronchopulmonary dysplasia (BPD), a lesion thought to be due to high levels of oxygen in inspired air. The incidence of BPD in newborn subjects with PLC was essentially the same as in those without PLC (7/16 or 44% vs 9/21 or 43%). Moreover, three newborn subjects with PLC and none without PLC showed renal tubular necrosis, a lesion usually associated with severe hypotension. This suggests that PLC is related to hypotension rather than to hyperoxia.
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PMID:Periventricular leukomalacia complex. Clinical and pathologic correlates. 689 32

D-Penicillamine, previously suspected to have a beneficial effect on the occurrence of severe retrolental fibroplasia among very low birth weight infants, was tested to determine the extent to which this drug modifies acute radiosensitivity on 3- to 4-day-old mice in comparison with adult animals. It was found that the radioprotective effect of penicillamine, given in doses of 3,000 mg/kg i.p. 60 min before whole-body exposure to 6-10 Gy of 60Co gamma rays, was greater in 3- to 4-day-old mice than in adult animals. These data seem to be compatible with the view that D-penicillamine, by virtue of its antioxidant action, may reduce the toxic effects associated with exposure of the newborn infant to hyperoxia, specifically retrolental fibroplasia and bronchopulmonary dysplasia.
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PMID:Age-related difference in radioprotective effect of D-penicillamine. 715 43

Pathophysiologic and biochemical (surfactant protein and phospholipid) features were studied in a baboon model of hyperoxia-induced bronchopulmonary dysplasia (BPD) and superimposed infection. A total of 20 baboons were delivered by hysterotomy at 76% of gestation (140 d of gestational age) and were randomized into four groups, consisting of two control and two injury groups. Animals constituting a group that was managed on a pro re nata (PRN) basis were ventilated with clinically appropriate oxygen for the 16-d experimental period and served as ventilatory controls. They underwent an initial period of 42 h during which they demonstrated evidence of hyaline membrane disease (HMD), but began recovery at 42 h and by Day 6 appeared to have maximally recovered. At the time of these animals' killing, concentrations of surfactant proteins, messenger ribonucleic acids (mRNAs), and phospholipids were similar to those of normal adult baboons. Gestational control animals were delivered and killed without ventilation at 156 d gestational age. Surfactant protein-A (SP-A) and phospholipid concentrations in these animals' lavage fluids were about 10% of those in the PRN animals. Animals with BPD were subjected to positive-pressure ventilation and an FIO2 of 1.0 for 11 d, followed by 5 d of an FIO2 sufficient to maintain PaO2 at 40 to 50 mm Hg. The animals with BPD and infection were treated in the same way as the BPD group, except that 10(8) Escherichia coli were instilled intratracheally on Day 11, concomitantly with the reduction in FIO2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Surfactant protein-A deficiency in a primate model of bronchopulmonary dysplasia. 776 49

Lung injury induced by 100% O2 over 6 days is characterized by markedly less alveolar fibrin and rare hyaline membranes in premature versus adult baboons. To determine the mechanism(s) underlying alveolar fibrin deposition in the evolution of hyaline membrane disease (HMD) through diffuse alveolar damage (DAD) and bronchopulmonary dysplasia (BPD), we measured procoagulant and fibrinolytic activities in lung lavage of premature baboons with HMD, those treated with 100% O2 for 6 days (DAD) or for 7 days followed by 14 days 80% O2 (BPD). Lavage procoagulant activity, mainly due to tissue factor associated with Factor VII, was increased by hyperoxia. Plasminogen-dependent fibrinolytic activity, due to both tissue plasminogen activator and urokinase, was stable or increased after hyperoxia. Plasminogen activator inhibitor 1 (PAI-1) was detectable in lavage of animals with HMD but not those with evolving DAD or BPD. Antiplasmin activity was stable or decreased. Although plasminogen was undetectable in lavage, D-dimer was increased in lavage of the groups exposed to hyperoxia versus HMD. The defect in plasminogen activator activity in lavage fluids of adult baboons with DAD induced by O2 does not occur in premature baboons with HMD, evolving DAD, or BPD. Expression of fibrinolytic activity in the lower respiratory tract of premature baboons is dependent on local access to plasminogen, which is present in relatively low concentrations in plasma of these animals.
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PMID:Pathways of fibrin turnover in lavage of premature baboons with hyperoxic lung injury. 811 20

Oxygen therapy in preterm infants is associated with bronchopulmonary dysplasia, but the relative importance of oxygen toxicity as compared to adverse effects of intubation and mechanical ventilation, remains uncertain. In freely-breathing neonatal rats, exposure to 100% oxygen for as little as 2 hr produced a significant reduction in lung DNA synthesis, evaluated by [3H]thymidine incorporation, without a concomitant effect on [3H]leucine incorporation into protein. These results indicate that hyperoxia has a selective deleterious effect on mitosis in developing lung.
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PMID:Immediate decline in DNA synthesis in neonatal rat lung caused by exposure to 100% oxygen. 835 12

Multiple insults may induce bronchopulmonary dysplasia (BPD) in premature infants, including the recently reported association of BPD with neonatal Ureaplasma urealyticum colonization. One mechanism of damage could involve stimulation of proinflammatory cytokine release from pulmonary fibroblasts. We therefore compared the effects of U. urealyticum, oxygen, and lipopolysaccharide (LPS) on the release of interleukin (IL)-1 beta, IL-6, and IL-8 from neonatal fibroblasts. Fibroblasts were grown in multiwell plates and divided into the following experimental conditions: fibroblasts alone, fibroblasts plus U. urealyticum (10,000 cfu/mL), and fibroblasts plus LPS (2 micrograms/mL). Plates were then exposed to room air or hyperoxia for 48 h, and supernatants were assayed for IL. U. urealyticum-infected fibroblasts produced a significant increase in IL-6 (P < .05) and a dramatic increase in IL-8 (P < .05) that was independent of hyperoxic exposure and significantly increased over that produced by LPS or hyperoxia alone. U. urealyticum is a potent inducer of fibroblast cytokine release in vitro and may contribute to the development of BPD.
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PMID:Induction of human neonatal pulmonary fibroblast cytokines by hyperoxia and Ureaplasma urealyticum. 839 7

Infants with BPD often suffer from chronic hypoxia and require supplemental oxygen (O2). This might affect the sensitivity of peripheral chemoreceptors. Therefore, we assessed peripheral chemoreceptor function in 25 infants with bronchopulmonary dysplasia (BPD) of varying severity, using the hyperoxic test. These infants were compared with 35 preterm infants who did not develop BPD. All infants were tested during the 40th week of postconceptional age and their mean postnatal age was 81.5 +/- 16.3 days. Sixty percent (15/25) of the BPD infants lacked a hyperoxic response, while the proportion of nonresponders to O2 among the other groups was 20% (7/35). The intensity of this response was negatively correlated to time spent on a ventilator and positively to time without supplemental oxygen. The intensity of chemoreceptor function was closely related to the severity of BPD; none of the infants with the most severe form of BPD (grade 3) showed a ventilatory response to hyperoxia. Furthermore, infants with BPD needed significantly longer time to increase their saturation than did non-BPD infants (4.7 and 9.3 sec, respectively). We conclude that many infants with BPD, particularly those with the most severe form of the disease, have abnormally functioning peripheral chemoreceptors.
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PMID:Blunted peripheral chemoreceptor response to hyperoxia in a group of infants with bronchopulmonary dysplasia. 857 Feb 99

The expression of lung manganese superoxide dismutase (MnSOD) mRNA and protein were examined in a premature baboon model of hyperoxia-induced bronchopulmonary dysplasia (BPD) and BPD superimposed with bacterial infection. When 140-d gestation baboons were delivered by hysterotomy and treated for 16 d with appropriate ventilatory and oxygen support (pro re nada controls), there was an increase in both MnSOD mRNA and protein compared with 140-d or 156-d gestation, nonventilated controls. The concentration of MnSOD protein was also elevated when the prematurely delivered baboons were ventilated with a high fraction of inspired O2 to produce a primate homolog of BPD, but there was a significant decrease in the concentration of MnSOD mRNA in BPD animals compared with pro re nada controls. In the lungs of premature baboons in which Escherichia coli infection was superimposed on hyperoxia-induced BPD, MnSOD mRNA was diminished to approximately the same extent as in BPD alone, but MnSOD protein was significantly increased compared with all other groups. Taken together these data indicate that the premature baboon is capable of mounting an antioxidant response and that increased MnSOD protein expression in BPD and BPD-infected premature baboons is regulated, at least in part, at a posttranscriptional level.
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PMID:Lung manganese superoxide dismutase protein expression increases in the baboon model of bronchopulmonary dysplasia and is regulated at a posttranscriptional level. 882 96

Since the description of bronchopulmonary dysplasia (BPD) in premature infants, the supplemental oxygen administered has been suspect in the etiology of BPD. This has prompted studies on the effect of hyperoxia on lung growth in neonatal animals. So far, these have not led to a treatment which either prevents or mitigates BPD. Another approach to investigate the effect of hyperoxia on the immature lung is to use lung explants from 12-d gestation mouse fetuses. Exposing explants to different concentrations of oxygen for 48 h, we found that exposures to oxygen both below (10%) and above (35% or greater) normoxia adversely affected branching morphogenesis and growth. The effect was irreversible at exposures of 50% oxygen and greater. To determine the role of reactive oxygen species (ROS) in the effect of hyperoxia, antioxidants and inhibitors of ROS formation were added to the incubating explants, and their influence on reducing the adverse effect of 50% oxygen was assessed. The combination of CuZn superoxide dismutase (SOD) and catalase, manganese SOD, manganese-3-tetrakis(1-methyl-4-pyridyl)porphorin, a low molecular weight SOD mimetic, and to a lesser extent, deferoximine, an antioxidant and inhibitor of hydroxyl radical formation, were successful in reducing the effect of 50% oxygen on morphogenesis. Not successful were N-nitro-L-arginine methyl ester (an inhibitor of nitric oxide synthase); allopurinol (an inhibitor of xanthine oxidase); N-acetylcysteine and ebselen (a glutathione peroxidase mimetic); Trolox (a synthetic tocopherol); catalase, and CuZnSOD used alone. These results provide evidence that superoxide anion and possibly hydroxyl radical are the ROS most likely responsible for the growth effects of hyperoxia on mouse fetal lung morphogenesis.
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PMID:Oxygen toxicity to the developing lung of the mouse: role of reactive oxygen species. 882 70

Pulmonary oxygen injury is classified by the development of tissue and alveolar edema, surfactant dysfunction, lung inflammation, and decreased pulmonary compliance. In neonates prolonged oxygen therapy is associated with the development of bronchopulmonary dysplasia. Recombinant DNA technology makes it possible to experimentally explore the role of specific proteins in the development of pulmonary oxygen injury. However, in vivo experiments require sensitive ways of identifying pulmonary oxygen injury early in its development. We therefore compared the sensitivities of several experimental assays used to assess pulmonary injury. We found that changes in pulmonary compliance were the most sensitive and showed significant differences after 72 hr of exposure to normobaric hyperoxia (FiO2 = 0.95), which correlated with a small change in the histology of the mice lungs. The concentration of protein in the bronchoalveolar lavage fluid was less sensitive and did not differ significantly until after 96 hr of exposure. The survival in hyperoxia also did not worsen until after 96 hr. The lung wet/ dry weight ratios was the least sensitive assay and did not increase until after 5 days of exposure to normobaric hyperoxia. We conclude that a decrease in pulmonary compliance is an early indicator of pulmonary oxygen injury and may be a better way to study the mechanisms and mediators of pulmonary oxygen injury.
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PMID:Decreased pulmonary compliance is an early indicator of pulmonary oxygen injury. 907 67


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