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

Monolayer cultures of fetal rat mixed lung cells respond to sublethal concentrations (50%) of oxygen by a reduced growth rate. Exposure to 95% O2 causes growth arrest and cell loss. In the presence of serum the addition of dexamethasone (5.5 nM), tri-iodothyronine (5.5 nM), or insulin (5 microU/ml) appeared to increase the cytotoxicity of 95% O2. Under growth-arrested conditions, in the absence of serum or elevated O2 concentrations, all three agents influence cellular antioxidant enzyme activities. Dexamethasone (0.055 nM) increased CuZn superoxide dismutase activity by 72% and glutathione peroxidase activity by 94%. Triiodothyronine (5.5 nM) increased CuZn superoxide dismutase activity 93%. Insulin (5 microU/ml) increased CuZn superoxide dismutase activity 90%, and catalase activity 58%. Dexamethasone, but not tri-iodothyronine or insulin, seems to have a protective effect against subsequent acute hyperoxia under serum-free conditions. Local non-hormonal factors may also influence lung cell responses to acute increases in oxygen concentrations, since cells acutely exposed to 50% or 95% O2 release a transferable factor(s) into their culture medium which increases antioxidant enzyme activities of non-hyperoxic lung cells.
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PMID:Hormonal and local factors influence antioxidant enzyme activity of rat fetal lung cells in vitro. 352 18

The purpose of this study was to assess whether breathing high or low concentrations of O2 could affect glucose turnover during exercise in man. Ten healthy subjects performed two constant work-rate exercise tests, one when the fraction of inspired O2 (FIO2) was 0.15 and the other at the same work rate but when the FIO2 was 0.80. The work rate for each subject was chosen so that blood lactate would be elevated during hypoxia, but would be lower during hyperoxia. Glucose appearance (Ra) and disappearance (Rd) were measured using the primed, constant infusion of [3-3H]glucose. Although the work rate was the same during hypoxia and hyperoxia in each subject, hypoxic exercise was accompanied by a significantly larger rest to exercise increase in Rd (delta Rd) compared with hyperoxia by 265%. Similarly, delta Ra was greater during hypoxia than during hyperoxia by 188%. Lactate to pyruvate ratios were significantly higher during hypoxic exercise suggesting a shift in the cell redox to a more reduced state. Insulin and glucagon were not affected by the FIO2, but both epinephrine and norepinephrine were increased during hypoxic exercise, which may explain the increase in Ra. The regulation of blood glucose during exercise in vivo appears to be dependent on the availability of oxygen to the working muscle cells.
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PMID:Glucose turnover in response to exercise during high- and low-FIO2 breathing in man. 352 22

Chronic injury to the developing lung results in cell proliferation and characteristic architectural changes. It is likely that growth factors produced and acting locally are important to these processes. Insulin-like growth factors I and II (IGF-I and IGF-II) are peptide growth factors expressed by lung cells. Roles for IGF-I and IGF-II in lung injury are suggested by their expression during lung development and by studies showing changes in IGF-I expression by activated alveolar macrophages, and increases in IGF-II peptide in oxidant arrested alveolar epithelial cells. To investigate whether the expression of IGF-I and IGF-II are changed with hyperoxic exposure, newborn rats were exposed to 80-90% oxygen for up to 6 wk and Northern hybridization analyses, in situ hybridization histochemistry, immunohistochemical staining, and reverse transcription-polymerase chain reaction (RT-PCR) studies were performed. Northern hybridization analyses of RNA extracted from whole lung showed increases in IGF-I and IGF-II mRNAs with prolonged hyperoxia. In situ hybridization histochemistry and immunohistochemical staining demonstrated spatial patterns of IGF-I and IGF-II expression similar to those seen during fetal lung development. In addition, alveolar macrophages express IGF-I and type II epithelial cells express IGF-II in control and oxygen-injured lung. These results suggest that in lung injury resident lung cells may re-express IGFs in a manner reminiscent of fetal development, and activated inflammatory cells may contribute to the proliferative response through autocrine and paracrine mechanisms.
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PMID:Re-emergence of a fetal pattern of insulin-like growth factor expression during hyperoxic rat lung injury. 916 Aug 36

It seems clear that the abundance of potential treatment options reflects the dearth of proved, effective options. Thus, although we appear to be on the brink of many potentially major breakthroughs in treatment, there currently remains a multitude of unanswered questions and the need for further study. At this point clinical recommendations must be limited to supportive care with moderation: oxygenation without hyperoxia; ventilation without hypocarbia; avoiding extremes of blood pressure, hematocrit, blood glucose, and body temperature. Unfortunately, data from human trials are extremely limited and often poorly controlled. Furthermore, even those few existing human studies have rarely--if ever--dealt with newborns infants (Table 2). In addition, many of the existing studies do not relate to generalized asphyxia but rather to single-organ reperfusion insults. Finally, there is the critical issue of timing. Unfortunately, much of the existing experimental data relate to prophylaxis rather than treatment, severely limiting their potential for clinical applicability. Interventions may have quite different effects when administered at different phases of this most intricate process. Hyperglycemia, for example, may be neuroprotective before an insult but detrimental if induced after an asphyxial episode. Conversely, the NMDA blocker MK-801 can adversely affect outcome when given before a global asphyxial insult but can reduce seizure-related damage when given during the hyperexcitability phase. Insulin-like growth factor is also neuroprotective only when given after an insult, but it is not helpful if given before. An intimate understanding of the pathophysiologic processes involved is essential before any attempts at applying the diverse data derived from numerous animal studies to the human situation in an intelligent manner. Future studies may focus on cocktails of different mixtures of the compounds discussed or on single multipotential drugs, which would make possible a multipronged approach. However, it is essential to investigate fully the potential for toxic drug interactions, as some combinations may be produce serious consequences. For example, Gluckman and Williams evaluated the potential of combining calcium channel blockers with NMDA receptor antagonists in hypoxic-ischemic rats and found that this combination led to rapid cardiovascular collapse. Other enticing approaches for future investigations will probably include some genetic-engineering-related studies in attempt to enhance endogenous antioxidant defenses with regulon stimulation or the administration of neurotrophic growth factors. Unavoidably, the trip from the laboratory to the bedside must of necessity be an arduous and rigorous one.
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PMID:Ischemia and reperfusion injury. The ultimate pathophysiologic paradox. 977 46

Hyperoxic exposure of the developing lung leads to characteristic peribronchial and mesenchymal fibroproliferative changes. We hypothesize that O2-induced changes in the neonatal lung are mediated by Insulin-like growth factor 1 (IGF-1) and IGF-1 receptor (IGF-1R). Lung explant cultures were prepared from 3-day-old neonatal rat pups and exposed to room air or 95% O2 for 72 h. Western blots and immunohistochemistry were used to determine if hyperoxia stimulated IGF-1 and IGF-1R, and to identify the cell types involved. Retinoic acid was used to learn if this would inhibit oxygen-induced cell proliferation. Hyperoxia induced a significant increase in thymidine incorporation (control, 54 +/- 9; hyperoxia, 254 +/- 24 dpm/nM DNA; mean +/- SEM; N = 3; P < 0.05). This was inhibited by 5 x 10(-5) M RA (149 +/- 18 dpm/nM DNA; P < 0.05) and by anti-IGF-1 antibody (115 +/- 25 dpm/nM DNA; P < 0.05; N = 3). BrdU labeling in the mesenchymal cells was significantly increased in mesenchymal cells after exposure to oxygen (91% higher than the room air control) but not in epithelial cells. This increase was inhibited in the presence of retinoic acid. Western blots showed IGF-1 protein was increased after 72 h of O2 exposure compared to room air exposure (57 +/- 7 compared to 32 +/- 5 densitometric units; P < 0.05; N = 3). The increase was inhibited when the cultures were exposed to 95% O2 in the presence of anti-IGF-1 antibody (28 +/- 4; P < 0.05; N = 3). IGF-1 protein decreased in the presence of retinoic acid after oxygen exposure but not in room air. Immunostaining of O2-exposed lung showed IGF-1 was most abundant in airway and alveolar epithelial cells. We conclude that hyperoxia increases cell proliferation by stimulating IGF-1 in the neonatal rat lung. Interaction of IGF-1 and IGF-1R is an important cell-cell communication mechanism in the developmental and repair processes of hyperoxic neonatal lung injury.
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PMID:Regulation of cell proliferation by insulin-like growth factor 1 in hyperoxia-exposed neonatal rat lung. 1191 39

Although controversial, animal and tissue studies indicate that carotid bodies are sensitive to changes in glucose as well as in oxygen, thereby functioning as metabolic sensors. This study was designed to test the hypothesis that carotid bodies in humans participate in the counter-regulatory response to insulin-induced hypoglycemia.Dopamine and hyperoxia were used to suppress the carotid bodies' responsiveness in 16 normal subjects. Insulin and glucose infusions were used to clamp the plasma glucose in a step-wise decrease to 2.5,mmol/l over 4 hours while counter-regulatory hormones were measured.The hypoglycemic trajectories were similar under all three interventions (dopa-mine, hyperoxia and control), but the total glucose infused was significantly larger for hyperoxia than for dopamine. Cortisol and epinephrine both showed the expected increase with hypoglycemia, but there was no difference among interventions. Glucagon and norepinephrine levels were increased by dopamine, but only the normalized increase in glucagon was lower with dopamine and hyperoxia than control.The decrease in total glucose required for the dopamine experiments was most likely due to the higher baseline glucagon and norepinephrine levels. Hyperoxia did require more infused glucose, indicating some increased insulin sensitivity, but it was not clearly due to a decrease in cortisol or epinephrine responses. Thus, we did not find direct evidence of the carotid bodies' role in glucose homeostasis in humans.
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PMID:The role of the carotid bodies in the counter-regulatory response to hypoglycemia. 1953 90

Insulin-like growth factor (IGF)-1 is increased in different models of acute lung injury, and is an important determinant of survival and proliferation in many cells. We previously demonstrated that treatment of mice with IGF-1 receptor-blocking antibody (A12) improved early survival in bleomycin-induced lung injury. We have now examined whether administration of A12 improved markers of lung injury in hyperoxia model of lung injury. C57BL/6 mice underwent intraperitoneal administration of A12 or control antibody (keyhole limpet hemocyanin [KLH]), then were exposed to 95% hyperoxia for 88-90 hours. Mice were killed and bronchoalveolar lavage (BAL) and lung tissue were obtained for analysis. Hyperoxia caused a significant increase in IGF levels in BAL and lung lysates. Peripheral blood neutrophils expressed IGF-1R at baseline and after hyperoxia. BAL neutrophils from hyperoxia-treated mice and patients with acute lung injury also expressed cell surface IGF-1R. A12-treated mice had significantly decreased polymorphonuclear cell (PMN) count in BAL compared with KLH control mice (P = 0.02). BAL from A12-treated mice demonstrated decreased PMN chemotactic activity compared with BAL from KLH-treated mice. Pretreatment of PMNs with A12 decreased their chemotactic response to BAL from hyperoxia-exposed mice. Furthermore, IGF-1 induced a dose-dependent chemotaxis of PMNs. There were no differences in other chemotactic cytokines in BAL, including CXCL1 and CXCL2. In summary, IGF blockade decreased PMN recruitment to the alveolar space in a mouse model of hyperoxia. Furthermore, the decrease in BAL PMNs was at least partially due to a direct effect of A12 on PMN chemotaxis.
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PMID:Effect of insulin-like growth factor blockade on hyperoxia-induced lung injury. 2249 12