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

The concomitant treatment of rats with bleomycin and hyperoxia results in synergistic development of pulmonary injury. We exposed rats to 70% oxygen for 72 hr following an intratracheal instillation of bleomycin (0.2 U/kg body wt). Animals were killed 15, 30, 60 and 90 days after treatment for hydroxyproline, cell kinetics, and histopathologic analysis. A 16% increase in hydroxyproline over controls was seen 15 days after treatment which was manifested by the proliferation phase of diffuse alveolar damage and an increase in cell labeling by tritiated thymidine. Thirty days after treatment the hydroxyproline remained elevated while lung injury appeared to be healing with a residual focal interstitial pneumonitis and a drop in cell labeling. Between 60 and 90 days, there was an additional significant increase in hydroxyproline to 44% over controls. Diffuse interstitial pneumonitis with fibrosis was observed. Cell labeling remained constant between 60 and 90 days. We conclude that the treatment of rats with bleomycin and hyperoxia results in slowly progressive pulmonary fibrosis. The increase in hydroxyproline in the chronic phase was not accompanied by an increase in cell proliferation, and therefore may have resulted from an increase in cellular production of hydroxyproline rather than increased number of cells producing collagen.
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PMID:Progressive pulmonary fibrosis in rats: a biochemical, cell kinetic, and morphologic analysis. 241 89

Adult BALB/c mice, which are sensitive to hyperoxia (LT50 = 4.5 days 100% O2), were made tolerant to 100% O2 after treatment with butylated hydroxytoluene (BHT). Following a single ip dose of 400 mg/kg, mice survived longer periods in O2 when exposed to O2 at 7, 14, and 21, but not 2 days, following BHT injection. The tolerance was most pronounced on Day 7 (LT50 = 9.6 days) and decreased with time (LT50 7.7 days on Day 14 and 7.3 days on Day 21). Glucose-6-phosphate dehydrogenase levels of whole lung homogenates following BHT exposure were elevated on Day 7 when expressed as per milligram of protein or DNA. Other antioxidant defenses were generally increased only when expressed on a per lung basis. Histopathology of lungs from BHT-treated mice revealed typical BHT-induced lung lesions. BHT treatment followed by long-term hyperoxic exposure produced additional damage to the lung manifested by the exudative phase of diffuse alveolar damage with 1 week of exposure. This was followed by the proliferative phase, then chronic interstitial pneumonitis and fibrosis with 2 and 6 weeks of exposure, respectively. Mice continued to survive in 100% O2 despite this damage. We conclude that pretreatment with BHT enhances O2 tolerance in mice, which may be mediated by induction of antioxidant defenses and also by cell renewal induced by BHT damage.
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PMID:Oxygen tolerance in mice following exposure to butylated hydroxytoluene. 318 20

The concomitant treatment of hamsters with bleomycin and hyperoxia results in a synergistic development of pulmonary injury. We exposed hamsters for 72 hr to 70% oxygen following a single intratracheal instillation of bleomycin (0.16 U/100 g body weight). Groups of 10 animals were killed at 3, 6, 10, 30, 60, 90, and 120 days after instillation for histopathologic and morphometric assessment. Diffuse alveolar damage developed acutely. At 30 days, the intense acute cellular infiltrate had subsided, leaving a focal interstitial pneumonitis. Morphometric quantitation at 10 days revealed that 33.5 +/- 5.3% (x +/- SE) of the lung was diseased; there was apparent healing by 30 days, when 10.5 +/- 2.0% of the lung was diseased. However, progression to diffuse pneumonitis with fibrosis was seen at 60, 90, and 120 days, when 30.2 +/- 4.9%, 38.5 +/- 5.8%, and 38.8 +/- 4.5% of the lung was diseased, respectively. In vivo pulmonary function studies on treated animals at 25 and 55 days showed decreasing dynamic compliance and increased minute ventilation, which corroborates the presence of interstitial fibrosis. We conclude that simultaneous treatment of hamsters with bleomycin and hyperoxia results in interstitial fibrosis with a distribution and progression that mimics human pulmonary fibrosis. This model appears ideally suited for the study of progressive fibrosis and will be useful when development of a widely distributed lesion is crucial.
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PMID:Progressive pulmonary fibrosis in hamsters. 619 99

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

Febrile-range hyperthermia (FRH) improves survival in experimental infections by accelerating pathogen clearance, but may also increase collateral tissue injury. We hypothesized that FRH would worsen the outcome of inflammation stimulated by a non-replicating agonist and tested this hypothesis in a murine model of pulmonary oxygen toxicity. Using a conscious, temperature-controlled mouse model, we showed that maintaining a core temperature at FRH (39 degrees C to 40 degrees C) rather than at euthermic levels (36.5 degrees C to 37 degrees C) during hyperoxia exposure accelerated lethal pulmonary vascular endothelial injury, reduced the inspired oxygen threshold for lethality, induced expression of granulocyte-colony stimulating factor, and expanded the circulating neutrophil pool. In these same mice, FRH augmented pulmonary expression of the ELR(+) CXC chemokines, KC and LPS-induced CXC chemokine, enhanced recruitment of neutrophils, and changed the histological pattern of lung injury to a neutrophilic interstitial pneumonitis. Immunoblockade of CXC receptor-2 abrogated neutrophil recruitment, reduced pulmonary vascular injury, and delayed death. These combined data demonstrate that FRH may enlist distinct mediators and effector cells to profoundly shift the host response to a defined injurious stimulus, in part by augmenting delivery of neutrophils to sites of inflammation, such as may occur in infections. In certain conditions, such as in the hyperoxic lung, this process may be deleterious.
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PMID:Febrile-range hyperthermia augments pulmonary neutrophil recruitment and amplifies pulmonary oxygen toxicity. 1275 56

Treatment of neonatal RDS in premature infants with intratracheal administration of natural surfactant has become gold standard therapy. Natural surfactant preparations mainly contain, apart from phospholipids, the surfactant associated proteins B and C (SP-B and SP-C). Both proteins are synthesized mainly in alveolar type-II cells and Clara-cells, SP-B, also in the gastrointestinal tract and the auditive tube. SP-B is encoded on chromosome 2 over a region with 11 exons, whereas the SP-C gene is localized on chromosome 8 in a region containing 6 exons. Transcription of both SP-B and SP-C is induced by TTF-1. Furthermore SP-1 and SP-3 are known as transcription factors for SP-B. The main function of SP-B and SP-C is to maintain physiologic surface properties enabeling adequate lung mechanics. A complete SP-B deficiency following homozygous mutations in the SP-B gene (e. g. 121-ins 2-mutation) therefore leads to severe respiratory failure postnatally, due to the lack of functional surfactant. On the other hand complete deficiency of SP-C causes chronic interstitial pneumonitis as well in infants as in adults depending on disease-modifiers yet unknown. Besides the surface tension lowering property, SP-B reveals immunological functions regarding its interaction with different proinflammatory cellular systems as well as other inflammatory mediators, e. g. following hyperoxia. For SP-C first studies have described modulation of inflammatory reactions in macrophages, suggesting similar immune-modulatory effects. Whereas basic effects on lung mechanisms of both lipophilic surfactant proteins seem to be well understood, their immunologic local pulmonary functions and effects on surfactant metabolism require further investigations.
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PMID:[Surfactant-associated proteins B and C: molecular biology and physiologic properties]. 1522 16