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

Analyzing his own findings and the data available in the literature, the author has found that free radicals are a connecting link in the development of early and prolonged adaptation. With rapid adaptation, they make a weighty contribution to the body's bactericidal protection and antimicrobial constitutional immunity. This role is mainly played by the oxygen-dependent phagocytic bactericidal system that generates active oxygen forms and by the inducible arginine-dependent connective tissue cell system that synthesizes nitrogen oxide. While performing, the above enzymatic systems spend their cell energy resources on two concurrent processes: the formation of free radical products and the work of ionic pumps that restore an intracellular ionic and osmotic balance. This causes the accelerated expenditure of the body's energy "currency" ATP and the development of energy deficiency in the cells and tissues. Energy shortage serves as a signal for triggering the cellular genetic apparatus to primarily induce the increased development of the cell energy system, namely that of mitochondria, and the activation of the key systems responsible for steady-state long-term individual adaptation of the immune system, antioxidative protection, etc. It has been now ascertained that there is a common pathogenetic link (excessive production of free radicals) in the mechanism responsible for the influence of not only infections on the body, but other environmental factors (fibrogenic dust, ionizing or ultraviolet radiation, cooling, toxic agents oxidized on cytochrome P-450, hypoxia, hyperoxia, etc.) and vital functions (physical overstrain, emotional stress, informational overload, etc.). The above factors all cause the same metabolic change in different ways: the production of higher quantities of active oxygen forms, nitrogen oxide, and other radical products. So the generation of free radicals is an universal connecting link of early and prolonged adaptation. The fact that there is a common link (the excessive production of radicals) in the mechanism of influence of environmental factors and vital activities makes the most important biological reserve (cross adaptation that lies in higher resistance to the whole complex of active influences at adaptation to one of them) serve as a preventive means. The most rapid increase in the production of free radicals and the development of energy-rich products are achieved by hypoxia. So the adaptive and preventive effect of dosage hypoxia are the most pronounced.
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PMID:[Free radical oxidation as a link of early and prolonged adaptation to environmental factors]. 1151 77

Detection of cerebral hypoxia-ischemia remains problematic in neonates. Near-infrared spectroscopy, a noninvasive bedside technology has potential, although thresholds for cerebral hypoxia-ischemia have not been defined. This study determined hypoxic-ischemic thresholds for cerebral oxygen saturation (SCO2) in terms of EEG, brain ATP, and lactate concentrations, and compared these values with CBF and sagittal sinus oxygen saturation (SVO2). Sixty anesthetized piglets were equipped with near-infrared spectroscopy, EEG, laser-Doppler flowmetry, and a sagittal sinus catheter. After baseline, SCO2 levels of less than 20%, 20% to 29%, 30% to 39%, 40% to 49%, 50% to 59%, 60% to 79%, or 80% or greater were recorded for 30 minutes of normoxic normocapnia, hypercapnic hyperoxia, or bilateral carotid occlusion with or without arterial hypoxia. Brain ATP and lactate concentrations were measured biochemically. Logistic and linear regression determined the SCO2, CBF, and SVO2 thresholds for abnormal EEG, ATP, and lactate findings. Baseline SCO2 was 68 + 5%. The SCO2 thresholds for increased lactate, minor and major EEG change, and decreased ATP were 44 +/- 1%, 42 +/- 5%, 37 +/- 1%, and 33 +/- 1%. The SCO2 correlated linearly with SVO2 (r = 0.98) and CBF (r = 0.89), with corresponding SVO2 thresholds of 23%, 20%, 13%, and 8%, and CBF thresholds (% baseline) of 56%, 52%, 42%, and 36%. Thus, cerebral hypoxia-ischemia near-infrared spectroscopy thresholds for functional impairment are SCO2 33% to 44%, a range that is well below baseline SCO2 of 68%, suggesting a buffer between normal and dysfunction that also exists for CBF and SVO2.
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PMID:Near-infrared spectroscopy cerebral oxygen saturation thresholds for hypoxia-ischemia in piglets. 1189 39

Changes in branchial vacuolar-type H(+)-ATPase B-subunit mRNA and Na+, K(+)-ATPase alpha- and beta-subunit mRNA and ATP hydrolytic activity were examined in smolting Atlantic salmon exposed to hyperoxic and/or hypercapnic fresh water. Pre-smolts, smolts, and post-smolts were exposed for 1 to 4 days to hyperoxia (100% O2) and/or hypercapnia (2% CO2). Exposure to hypercapnic water for 4 days consistently decreased gill vacuolar-type H(+)-ATPase B-subunit mRNA levels. Salmon exposed to hyperoxia had either decreased or unchanged levels of gill B-subunit mRNA. Combined hyperoxia + hypercapnia decreased B-subunit mRNA levels, although not to the same degree as hypercapnic treatment alone. Hyperoxia generally increased Na+, K(+)-ATPase alpha- and beta-subunit mRNA levels, whereas hypercapnia reduced mRNA levels in presmolts (beta) and smolts (alpha and beta). Despite these changes in mRNA levels, whole tissue Na+, K(+)-ATPase activity was generally unaffected by the experimental treatments. We suggest that the reduced expression of branchial vacuolar-type H(+)-ATPase B-subunit mRNA observed during internal hypercapnic acidosis may lead to reduction of functional V-type H(+)-ATPase abundance as a compensatory response in order to minimise intracellular HCO3- formation in epithelial cells.
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PMID:Vacuolar-type H(+)-ATPase and Na+, K(+)-ATPase expression in gills of Atlantic salmon (Salmo salar) during isolated and combined exposure to hyperoxia and hypercapnia in fresh water. 1191 Oct 75

Blood flow to contracting skeletal muscle is tightly coupled to the oxygenation state of hemoglobin. To investigate if ATP could be a signal by which the erythrocyte contributes to the regulation of skeletal muscle blood flow and oxygen (O2) delivery, we measured circulating ATP in 8 young subjects during incremental one-legged knee-extensor exercise under conditions of normoxia, hypoxia, hyperoxia, and CO+normoxia, which produced reciprocal alterations in arterial O2 content and thigh blood flow (TBF), but equal thigh O2 delivery and thigh O2 uptake. With increasing exercise intensity, TBF, thigh vascular conductance (TVC), and femoral venous plasma [ATP] augmented significantly (P<0.05) in all conditions. However, with hypoxia, TBF, TVC, and femoral venous plasma [ATP] were (P<0.05) or tended (P=0.14) to be elevated compared with normoxia, whereas with hyperoxia they tended to be reduced. In CO+normoxia, where femoral venous O2Hb and (O2+CO)Hb were augmented compared with hypoxia despite equal arterial deoxygenation, TBF and TVC were elevated, whereas venous [ATP] was markedly reduced. At peak exercise, venous [ATP] in exercising and nonexercising limbs was tightly correlated to alterations in venous (O2+CO)Hb (r2=0.93 to 0.96; P<0.01). Intrafemoral artery infusion of ATP at rest in normoxia (n=5) evoked similar increases in TBF and TVC than those observed during exercise. Our results in humans support the hypothesis that the erythrocyte functions as an O2 sensor, contributing to the regulation of skeletal muscle blood flow and O2 delivery, by releasing ATP depending on the number of unoccupied O2 binding sites in the hemoglobin molecule.
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PMID:Erythrocyte and the regulation of human skeletal muscle blood flow and oxygen delivery: role of circulating ATP. 1245 91

High concentrations of oxygen (hyperoxia) are known to cause cellular injury and death. The heat shock response is a highly conserved cellular defense mechanism that protects cells against various environmental stressors, including hyperoxia. Herein we determined the role of heat shock factor-1 (HSF-1), a major component of the heat shock response, in protecting cells against hyperoxia. Embryonic fibroblasts from HSF-1-null mutant mice (HSF-1 -/- cells) were compared to wild-type embryonic fibroblasts (HSF-1 +/+ cells) following 24 hours' exposure to room air or hyperoxia (95% O(2)). Acute survival in hyperoxia was decreased in HSF-1 -/- cells as compared to HSF-1 +/+ cells. Intracellular ATP levels were significantly lower in the HSF-1 -/- cells as compared to the HSF-1 +/+ cells exposed to hyperoxia. Isoprostane levels, a marker of membrane lipid peroxidation, were significantly higher in the HSF-1 -/- cells as compared to the HSF-1 +/+ cells exposed to hyperoxia. Restoration of HSF-1 in the HSF-1 -/- cells by stable transfection with a HSF-1 expression plasmid improved survival in hyperoxia when compared to HSF-1 -/- cells stably transfected with the empty expression vector. Hyperoxia increased activation of HSF-1 in HSF-1 +/+ cells and in HSF-1 -/- cells stably transfected with the HSF-1 expression plasmid. These data demonstrate that HSF-1 plays an important role in conferring resistance to hyperoxia in vitro.
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PMID:Ablation of the heat shock factor-1 increases susceptibility to hyperoxia-mediated cellular injury. 1249 36

Respiratory failure is a serious consequence of lung cell injury caused by treatment with high inhaled oxygen concentrations. Human lung microvascular endothelial cells (HLMVEC) are a principal target of hyperoxic injury (hyperoxia). Cell stress can cause release of ATP, and this extracellular nucleotide can activate purinoreceptors and mediate responses essential for survival. In this investigation, exposure of endothelial cells to an oxidative stress, hyperoxia, caused rapid but transient ATP release (20.03 +/- 2.00 nm/10(6) cells in 95% O(2) versus 0.08 +/- 0.01 nm/10(6) cells in 21% O2 at 30 min) into the extracellular milieu without a concomitant change in intracellular ATP. Endogenously produced extracellular ATP-enhanced mTOR-dependent uptake of glucose (3467 +/- 102 cpm/mg protein in 95% oxygen versus 2100 +/- 112 cpm/mg protein in control). Extracellular addition of ATP-activated important cell survival proteins like PI 3-kinase and extracellular-regulated kinase (ERK-1/2). These events were mediated primarily by P2Y receptors, specifically the P2Y2 and/or P2Y6 subclass of receptors. Extracellular ATP was required for the survival of HLMVEC in hyperoxia (55 +/- 10% surviving cells with extracellular ATP scavengers [apyrase + adenosine deaminase] versus 95 +/- 12% surviving cells without ATP scavengers at 4 d of hyperoxia). Incubation with ATP scavengers abolished ATP-dependent ERK phosphorylation stimulated by hyperoxia. Further, ERK activation also was found to be important for cell survival in hyperoxia, as treatment with PD98059 enhanced hyperoxia-mediated cell death. These findings demonstrate that ATP release and subsequent ATP-mediated signaling events are vital for survival of HLMVEC in hyperoxia.
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PMID:Extracellular ATP-mediated signaling for survival in hyperoxia-induced oxidative stress. 1476 47

This study compared the effects of inspiring either a hyperoxic (60% O(2)) or normoxic gas (21% O(2)) while cycling at 70% peak O(2) uptake on 1) the ATP derived from substrate phosphorylation during the initial minute of exercise, as estimated from phosphocreatine degradation and lactate accumulation, and 2) the reliance on carbohydrate utilization and oxidation during steady-state cycling, as estimated from net muscle glycogen use and the activity of pyruvate dehydrogenase (PDH) in the active form (PDH(a)), respectively. We hypothesized that 60% O(2) would decrease substrate phosphorylation at the onset of exercise and that it would not affect steady-state exercise PDH activity, and therefore muscle carbohydrate oxidation would be unaltered. Ten active male subjects cycled for 15 min on two occasions while inspiring 21% or 60% O(2), balance N(2). Blood was obtained throughout and skeletal muscle biopsies were sampled at rest and 1 and 15 min of exercise in each trial. The ATP derived from substrate-level phosphorylation during the initial minute of exercise was unaffected by hyperoxia (21%: 52.2 +/- 11.1; 60%: 54.0 +/- 9.5 mmol ATP/kg dry wt). Net glycogen breakdown during 15 min of cycling was reduced during the 60% O(2) trial vs. 21% O(2) (192.7 +/- 25.3 vs. 138.6 +/- 16.8 mmol glycosyl units/kg dry wt). Hyperoxia had no effect on PDH(a), because it was similar to the 21% O(2) trial at rest and during exercise (21%: 2.20 +/- 0.26; 60%: 2.25 +/- 0.30 mmol.kg wet wt(-1).min(-1)). Blood lactate was lower (6.4 +/- 1.0 vs. 8.9 +/- 1.0 mM) at 15 min of exercise and net muscle lactate accumulation was reduced from 1 to 15 min of exercise in the 60% O(2) trial compared with 21% (8.6 +/- 5.1 vs. 27.3 +/- 5.8 mmol/kg dry wt). We concluded that O(2) availability did not limit oxidative phosphorylation in the initial minute of the normoxic trial, because substrate phosphorylation was unaffected by hyperoxia. Muscle glycogenolysis was reduced by hyperoxia during steady-state exercise, but carbohydrate oxidation (PDH(a)) was unaffected. This closer match between pyruvate production and oxidation during hyperoxia resulted in decreased muscle and blood lactate accumulation. The mechanism responsible for the decreased muscle glycogenolysis during hyperoxia in the present study is not clear.
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PMID:Effects of hyperoxia on skeletal muscle carbohydrate metabolism during transient and steady-state exercise. 1537 50

We have shown previously with in vivo and in vitro animal models that the lens epithelium, in contrast to the nucleus, is remarkably resistant to hyperoxia. The main purpose of this study was to investigate the mRNA response of cultured human lens epithelial cells (LECs) to challenge by a high level of hyperbaric oxygen. Cells were treated for 3 hr with 50 atm of 99% O2, and then cultured normally for various times up to 11 days. Although the cells appeared normal immediately after the O2-treatment, they failed to grow and suffered 50% cell loss, as well as significant mitochondrial damage, during normal post-culture. Growth of the cells resumed after 3 days and by day 11, the number of O2-treated cells was the same as the controls. Remarkably, the 3 hr O2-treatment produced no immediate effects on either the cellular level of GSH, or on the activities of a number of antioxidant enzymes including glyceraldehyde-3-phosphate dehydrogenase, which is generally regarded as being highly sensitive to oxidation. In contrast, the activity of thioredoxin reductase (TrxR) was severely affected by the O2, decreasing by 51% after the 3 hr exposure. O2-induced death of the cells appeared to be caused by loss of ATP since a 31% decrease in ATP level occurred immediately after the O2-treatment, in spite of a 46% increase in lactate production. Analysis with real-time PCR showed a maximum 3-6-fold increase in mRNA levels 9 hr after the 3 hr O2-exposure for the enzymes heme oxygenase-1 (HO-1), MnSOD and TrxR1 (the cytoplasmic form of TrxR). These results were confirmed with the use of one-step RT-PCR and Northern blotting. Initial upregulation of message for HO-1 occurred a few hours before any upregulation of MnSOD could be detected, suggesting that release of free iron from the degradation of heme by HO-1 may have played a role in the upregulation of the dismutase. No significant changes in mRNA levels were observed for the antioxidant enzymes catalase, CuZnSOD, glutathione reductase and glutathione peroxidase, or for the antioxidant protein thioredoxin. Recovery of TrxR activity over a 4-day period appeared to parallel the return of the cells to a normal rate of growth. The results indicate that damaging effects of hyperoxia on cultured LECs occur primarily in the mitochondria, rather than in the cytoplasm. Cells avoid O2-induced cell death, and return to a normal rate of proliferation by upregulating mRNA levels for HO-1, MnSOD and TrxR1. It appears that full activity of TrxR1, an enzyme required for the production of deoxyribonucletides for DNA synthesis, is essential for the normal growth of O2-challenged LECs.
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PMID:Thioredoxin reductase may be essential for the normal growth of hyperbaric oxygen-treated human lens epithelial cells. 1564 22

The cores of rabbit plaques in vivo are hypoxic, suggesting that ATP depletion due to an insufficient supply of oxygen and nutrients could contribute to macrophage death in atherosclerotic plaques. During hypoxia, however, macrophages maintain ATP levels by anaerobic glycolysis. To directly assess ATP and glucose metabolites in plaques in vivo, we used bioluminescence imaging to map the concentrations of ATP, glucose, glycogen, and lactate in normal and atherosclerotic rabbit aortas in vivo. Hypoxia was assessed with NITP (7-(4'-(2-nitroimidazol-1-yl)-butyl)-theophylline). Normal aortas and plaques <500 microm thick were not hypoxic and had homogenous concentrations of energy metabolites. In plaques >500 microm thick, however, the cores were characterized by ATP depletion, low concentrations of glucose and glycogen, and a high concentration of lactate. A majority of ATP-depleted macrophages within the core were viable but severely hypoxic and glucose depleted. Hyperoxia in vitro reversed the ATP depletion in macrophages in viable areas of the core. Our findings suggest that ATP depletion contributes to the death of macrophages in atherosclerotic lesions and to the formation of a necrotic core.
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PMID:ATP depletion in macrophages in the core of advanced rabbit atherosclerotic plaques in vivo. 1640 94

Blood flow to dynamically contracting myocytes is regulated to match O(2) delivery to metabolic demand. The red blood cell (RBC) itself functions as an O(2) sensor, contributing to the control of O(2) delivery by releasing the vasodilators ATP and S-nitrosohaemoglobin with the offloading of O(2) from the haemoglobin molecule. Whether RBC number is sensed remains unknown. To investigate the role of RBC number, in isolation and in combination with alterations in blood oxygenation, on muscle and systemic perfusion, we measured local and central haemodynamics during one-legged knee-extensor exercise ( approximately 50% peak power) in 10 healthy males under conditions of normocythaemia (control), anaemia, anaemia + plasma volume expansion (PVX), anaemia + PVX + hypoxia, polycythaemia, polycythaemia + hyperoxia and polycythaemia + hypoxia, which changed either RBC count alone or both RBC count and oxyhaemoglobin. Leg blood flow (LBF), cardiac output (Q) and vascular conductance did not change with either anaemia or polycythaemia alone. However, LBF increased with anaemia + PVX (28 +/- 4%) and anaemia + PVX + hypoxia (46 +/- 6%) and decreased with polycythaemia + hyperoxia (18 +/- 5%). LBF and Q with anaemia + PVX + hypoxia (8.0 +/- 0.5 and 15.8 +/- 0.7 l min(-1), respectively) equalled those during maximal knee-extensor exercise. Collectively, LBF and vascular conductance were intimately related to leg arterial-venous (a-v) O(2) difference (r(2)= 0.89-0.93; P < 0.001), suggesting a pivotal role of blood O(2) gradients in muscle microcirculatory control. The systemic circulation accommodated to the changes in muscle perfusion. Our results indicate that, when coping with severe haematological challenges, local regulation of skeletal muscle blood flow and O(2) delivery primarily senses alterations in the oxygenation state of haemoglobin and, to a lesser extent, alterations in the number of RBCs and haemoglobin molecules.
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PMID:Erythrocytes and the regulation of human skeletal muscle blood flow and oxygen delivery: role of erythrocyte count and oxygenation state of haemoglobin. 1643 30


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