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

Exposure to high concentrations of oxygen in the neonatal period may impair lung growth and is a major contributing factor to the development of bronchopulmonary dysplasia. Cell death from hyperoxic injury may occur through either an apoptotic or nonapoptotic pathway, and we were interested in determining the type of cell death that occurs in the lung of neonatal mice exposed to hyperoxia. We found increased levels of Bax messenger RNA, a gene associated with apoptosis, in the lungs of neonatal mice born and raised in 92% hyperoxia. We next determined the extent of apoptosis taking place in the lungs of neonatal mice exposed to hyperoxia using terminal deoxyribonucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling in 3.5-, 4.5-, and 5.5-d-old neonatal lung. The number of apoptotic cells in peripheral lung was significantly higher in the 3.5-, 4.5-, and 5.5-d-old mice treated with oxygen compared with that in the room-air control mice. Further, the number of apoptotic cells in the lung increased with longer exposure duration. In murine lung bronchus cells exposed to hyperoxia, growth arrest occurred after 48 h of oxygen exposure. Using annexin V binding, necrotic cell death was found to be the major form of cell death in these cells after 72 h of hyperoxic exposure. We conclude that 92% hyperoxia causes significant lung injury in neonatal mice exposed to hyperoxia, and that the number of apoptotic cells in the lung increases the longer the duration of exposure. The increase in apoptosis from hyperoxic exposure during a critical period of lung development may be an important factor in the impaired lung growth and remodeling that occur in animals exposed to high oxygen concentrations. Finally, it appears that hyperoxic injured cells in neonatal lung undergo both apoptotic and nonapoptotic cell death.
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PMID:Apoptosis in neonatal murine lung exposed to hyperoxia. 1150 23

Neutrophil influx in lung injury is controlled in part by chemokines acting through the receptor, CXCR2. To avoid adverse effects of steroids typically used to modify inflammation, we evaluated the effects of competitive blockade of CXCR2 in rats on neutrophil function in vitro and on neutrophil influx in vivo in hyperoxia-induced newborn lung injury, a model of bronchopulmonary dysplasia. In vitro, SB-265610 antagonizes rat cytokine-induced neutrophil chemoattractant-1 (CINC-1)-induced calcium mobilization, IC50 = 3.7 nM, and rat neutrophil chemotaxis in a concentration-dependent manner, IC50 = 70 nM. In vivo, newborn rats exposed to 95% O2 for 8 days had increased lung neutrophil content. Injection with 1 to 3 mg/kg SB-265610 on days 3 to 5 reduced hyperoxia-induced neutrophil accumulation in bronchoalveolar lavage and whole lung myeloperoxidase accumulation at the highest doses. To determine whether these effects might be due in part to increased neutrophil apoptosis, peripheral neutrophils were cultured with and without SB-265610. Apoptosis was assessed by morphology, viability, and terminal transferase deoxyuridine triphosphatidyl nucleotide nick-end labeling. Treatment of neutrophils with CINC-1 reduced apoptosis compared with untreated neutrophils. SB-265610 reduced the antiapoptotic effect of CINC-1 to the levels of those untreated with CINC-1. A selective CXCR2 antagonist may be useful in diseases where neutrophil-mediated exacerbation is present.
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PMID:Nonpeptide CXCR2 antagonist prevents neutrophil accumulation in hyperoxia-exposed newborn rats. 1156 Oct 67

Immaturity and oxygen toxicity have been implicated in the pathogenesis of the neonatal disease bronchopulmonary dysplasia. The present study aimed to investigate the use of magnetic resonance imaging (MRI) to assess hyperoxia-mediated lung injury in the term and premature neonate. Term (gestation, 22 d) and premature (21 d) rat pups were exposed to hyperoxia (>95%) or air for a 6-d period (n = 7) and assessed for lung damage by MRI. Pulmonary signal intensities of T1-weighted images were significantly increased in both hyperoxia-exposed term and premature neonates, relative to air-breathing controls (p < 0.01). T2-weighted MRI signal intensities were also greater in premature and term rat pups exposed to hyperoxia, but failed to reach significance (p > 0.05). Elevated MRI pulmonary signal intensities may have represented an increase in magnetic resonance-detectable free water, possibly indicating an increase in edema. Corresponding histologic evidence of lung injury was detected in both term and premature rat pups exposed to hyperoxia. Histologic samples indicated focal regions of alveolar hemorrhage, immune cell infiltration, edema, and collapse in both term and premature rat neonates exposed to hyperoxia. Alveolar air space was assessed (n = 5) by light microscopy within a 0.5 mm2 region of the superior left and inferior right pulmonary lobes of each treatment group. Alveolar area of the superior left lung lobe of the premature hyperoxia treatment group was significantly smaller than other treatment groups (p < 0.05). Reduced area for respiratory exchange was probably a result of observed focal areas of edema and collapse. MRI-detectable increases in lung signal intensity may have represented an increase in hyperoxia-induced pulmonary edema in the 6-d-old rat neonate. Increases in signal intensity correlated with the appearance of edema in pulmonary histologic samples. Premature delivery had a less defined effect on lung injury but possibly exacerbated hyperoxia-mediated pulmonary damage.
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PMID:Magnetic resonance imaging of pulmonary damage in the term and premature rat neonate exposed to hyperoxia. 1156 94

Bronchopulmonary dysplasia is the most common cause of chronic pulmonary disease in premature infants. Airway inflammation appears to play a major pathogenetic role together with barotrauma and oxygen toxicity. The aim of the present study was to determine the effect of a 15-d exposure to moderate hyperoxia (FiO2, 50%) on airway reactivity and inflammatory response in neonatal and adult rats. We studied in isolated tracheal rings the 1) isometric contraction to cumulative concentrations of carbachol (10(-8) to 10(-3) M); 2) epithelial, submucosal, smooth muscle, and connective tissue surface area; and 3) distribution of inflammatory cells (mastocytes, granulocytes, macrophages) by using MAb. Reactivity to carbachol was significantly increased in the hyperoxic pups, in which a 13% increase in tracheal smooth muscle surface area was observed. Type-I mast cells and macrophages (submucosa and connective tissue) and granulocytes (connective tissue) were increased in the neonatal hyperoxic group. Hyperoxia did not influence functional, morphometric, or cellular data in adult rats. In conclusion, exposure of newborn rats to moderate hyperoxia induces airway hyperresponsiveness and histologic changes similar to those reported in bronchopulmonary dysplasia. Hyperresponsiveness may be ascribed to an increase in smooth muscle related to the release of yet undetermined mediators by inflammatory cells infiltrating the airways. Lung immaturity definitely plays a role because similar alterations are not observed in adult rats.
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PMID:Prolonged moderate hyperoxia induces hyperresponsiveness and airway inflammation in newborn rats. 1156 96

Normal pulmonary vascular development is the result of a complex interplay of growth factors, including vascular endothelial growth factor (VEGF) and the angiopoietins. Injury to the developing lung, whether due to hyperoxia or mechanical ventilation, results in disordered vascular development, ranging from an apparent arrest of microvascular development in milder injury to extensive microvascular derangement in more severe injury. Alterations in vascular growth factors may participate in these injuries. During injury to the developing animal lung, VEGF abundance is markedly decreased. In models of post-injury recovery, up-regulation of VEGF accompanies the re-establishment of normal vasculature. Alterations in lung VEGF levels in human premature infants are less clear cut. However, among humans premature newborns who later go on to develop bronchopulmonary dysplasia (BPD), VEGF production is decreased in comparison to those newborns who recover. Other angiogenic factors, such as the CXC ELR+ chemokines, are also altered in injury to the developing lung, but their specific roles in vascular injury are less clear. Strategies that enhance microvascular integrity, whether through attenuating alterations in vascular growth factors or by other means, also improve the outcome of lung injury. Such therapies may eventually offer hope in human BPD.
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PMID:The role of vascular growth factors in hyperoxia-induced injury to the developing lung. 1208 14

A heparin-binding growth factor, midkine, is the product of a retinoic acid-responsive gene. Since retinol plays critical roles in lung development and treatment of bronchopulmonary dysplasia, and midkine has been implicated in the maturation of lung explants and in cytoprotection, we herein examined midkine expression during postnatal development of the lungs and hyperoxic lung injury. Midkine protein transiently increased to a maximum level at around 4 days postnatal. Immunohistochemistry revealed that the amounts of midkine increased in resident alveolar cells, but not in smooth muscle cells or the large airway epithelium. If neonatal mice were exposed to >95% oxygen, lung development was impaired and midkine expression was suppressed. In contrast, when adult mouse lungs as well as in vitro cultured lung adenocarcinoma cells were exposed to hyperoxia, midkine expression was not affected. Furthermore, a pronounced induction of midkine by retinoic acid was observed in neonatal lungs. The results indicate that midkine expression is associated with postnatal lung development, but not necessarily with hyperoxic cell damage.
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PMID:Midkine expression is associated with postnatal development of the lungs. 1220 52

Preterm infants lack adequate surfactant production and often require oxygen support for adequate oxygenation. Prolonged oxygen treatment leads to the development of bronchopulmonary dysplasia (BPD), a disease process characterized by the blunting of alveolarization and proliferation of myofibroblasts. In the present study, we investigated metabolic adaptive changes in cultured fibroblasts isolated from immature (d18) and near-term (d21), fetal rat lungs in response to normoxic (21%) and hyperoxic (95%) exposures. We used the [1,2-13C2]D-glucose tracer and gas chromatography/mass spectrometry to characterize glucose carbon redistribution between the nucleic acid ribose, lactate, and palmitate synthetic pathways, and reverse transcriptase-polymerase chain reaction to assess adipose differentiation related protein (ADRP) mRNA expression in response to hyperoxic exposure. Exposure to hyperoxia at each passage caused decrease (*, p<0.05 vs. 21% O2) in ADRP mRNA expression in the d18 fibroblasts. This passage-dependent transdifferentiation is accompanied by a moderate (9-20%) increase in the synthesis of nucleic acid ribose from glucose through the non-oxidative steps of the pentose cycle. In contrast, d18 fibroblasts showed over an 85% decrease in the de novo synthesis of palmitate from glucose, while d21 fibroblasts showed a less pronounced 32-38% decrease in de novo lipid synthesis in hyperoxia-exposed cultures. It can be concluded from these studies that: (1) there is a maturation dependent sensitivity to hyperoxia; (2) transdifferentiation of flbroblast as demonstrated by changes in ADRP expression is accompanied by metabolic enzymes changes affecting ribose acid synthesis from glucose, and (3) hyperoxia specifically inhibits lipogenesis from glucose. Hyperoxia-induced metabolic changes thus play a key role in the transdifferentiation of lung fibroblasts to myofibroblasts and the pathogenesis of BPD.
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PMID:Oxygen-induced metabolic changes and transdifferentiation in immature fetal rat lung lipofibroblasts. 1240 71

Superoxide anion and other oxygen-free radicals have been implicated in the pathogenesis of bronchopulmonary dysplasia. We tested the hypothesis that a catalytic antioxidant metalloporphyrin AEOL 10113 can protect against hyperoxia-induced lung injury using a fetal baboon model of bronchopulmonary dysplasia. Fetal baboons were delivered by hysterotomy at 140 days of gestation (term = 185 days) and given 100% oxygen for 10 days. Morphometric analysis of alveolar structure showed that fetal baboons on 100% oxygen alone had increased parenchymal mast cells and eosinophils, increased alveolar tissue volume and septal thickness, and decreased alveolar surface area compared with animals given oxygen as needed. Treatment with AEOL 10113 (continuous intravenous infusion) during 100% oxygen exposure partially reversed these oxygen-induced changes. Hyperoxia increased the number of neuroendocrine cells in the peripheral lung, which was preceded by increased levels of urine bombesin-like peptide at 48 hours of age. AEOL 10113 inhibited the hyperoxia-induced increases in urine bombesin-like peptide and numbers of neuroendocrine cells. An increasing trend in oxygenation index over time was observed in the 100% oxygen group but not the mimetic-treated group. These results suggest that AEOL 10113 might reduce the risk of pulmonary oxygen toxicity in prematurely born infants.
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PMID:A catalytic antioxidant attenuates alveolar structural remodeling in bronchopulmonary dysplasia. 1250 67

Neonatal rats exposed to 60% O(2) for 14 days develop lung changes compatible with human bronchopulmonary dysplasia and pulmonary hypertension. Our aim was to evaluate and compare the newborn and adult rat pulmonary vascular and airway smooth muscle force generation and relaxation potential after exposure to 60% O(2) for 14 days. Vascular and airway intrapulmonary rings 100 microm in diameter were mounted on a myograph and bathed in Krebs-Henseleit solution bubbled with air- 6% CO(2) at 37 degrees C. Significant age-dependent changes in intrapulmonary arteries and their neighboring airway muscle properties were observed. Whereas hyperoxia enhanced force in neonatal vascular and airway muscle, the opposite was seen in adult samples. No changes in endothelium-dependent vascular relaxation were observed at either age, but the dose response to an endothelium-independent NO donor was altered. In the newborn experimental animals, the relaxation was reduced, whereas, in their adult counterparts, it was enhanced. After O(2) exposure, the bronchial muscle relaxation response to epithelium-dependent and -independent stimulation was not altered in either age group, whereas the epithelium-dependent response was decreased only in the adult. The antioxidant Trolox, or an endothelin-A and -B receptor antagonist, reversed the vascular and airway muscle's hyperoxia-induced changes. We conclude that chronic O(2) exposure in the newborn rat results in enhanced lung vascular and airway muscle contraction potential via a mechanism involving reactive oxygen species and the endothelin pathway. The present findings also suggest that the newborn is more susceptible to airway hyperresponsiveness after chronic O(2) exposure.
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PMID:Chronic O2 exposure enhances vascular and airway smooth muscle contraction in the newborn but not adult rat. 1256 76

Macrophage-derived cytokines may provoke the inflammatory response in lung injury. Because macrophage influx is a prominent feature of the cellular inflammatory response accompanying the development of bronchopulmonary dysplasia, we hypothesized that blocking macrophage influx would reduce overall cellular influx and oxidative damage. Newborn rats were exposed at birth to 95% O(2) or air for 1 wk, and hyperoxia-exposed pups were injected with anti-monocyte chemoattractant protein-1 (MCP-1) or IgG control on days 3-5. MCP-1 was increased in bronchoalveolar lavage fluid and in histological sections from the 95% O(2)-exposed, IgG-injected pups compared with air-exposed controls. At 1 wk, anti-MCP-1-treated pups had reduced leukocyte numbers, both macrophages and neutrophils, in bronchoalveolar lavage fluid compared with IgG-treated controls. Cytokine-induced neutrophil chemoattractant-1, the rat analog of IL-8, was not significantly decreased in lavage fluid but was reduced in lung cells in anti-MCP-1-treated pups. Tissue carbonyls, a measure of protein oxidation, were decreased in anti-MCP-1-treated pups. Anti-MCP-1 treatment prevented neutrophil influx and reduced protein oxidation in hyperoxia-exposed newborn rats.
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PMID:Antimacrophage chemokine treatment prevents neutrophil and macrophage influx in hyperoxia-exposed newborn rat lung. 1258 6


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