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

In anaesthetized cats, in which the cerebrospinal fluid bicarbonate concentration was varied by a ventriculocisternal perfusion technique, the ventilatory response to CO2 during hyperoxia could be satisfactorily described by VE = S(PCSFCO2 -B). Both the slope S and the intercept B were positively and linearly related to the CSF bicarbonate concentration. Assuming that the PCSFCO2 is equal to the PCO2 in extracellular fluid, it can be shown that VE is a linear, but not a unique function of the [H+] at the site of the chemoreceptors; the slope of this relation varies with the bicarbonate concentration at that site, possibly due to chemical complex formation between HCO-3 and Ca2+ or Mg2+. Changes in the B-value were related to the location of the central chemoreceptors with the models of Pappenheimer and Berndt aand their coworkers. It was found that changes in the CSF bicarbonate concentration are reflected for 60 per cent at the site of the central chemoreceptors, and that this was independent of the cerebral perfusion. Using Berndt's model a distance between CSF and central chemoreceptors of approximately 100 micron was found; this calculated distance is relatively insensitive to relationship (logarithmic or not) between ventilation and H+ concentration and to changes in cerebral perfusion, owing to the approximate nature of the diffusion model.
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PMID:Influence of the CSF bicarbonate concentration on the ventilatory response to CO2 in relation to the location of the central chemoreceptors. 74 Nov 4

To evaluate the regulation of endothelial cell Cu,Zn-SOD, we have exposed bovine pulmonary artery endothelial cells in culture to hyperoxia and hypoxia, second messengers or related agonists, hormones, free radical generating systems, endotoxin, and cytokines and have measured Cu,Zn-SOD protein of these cells by an ELISA developed in our laboratory. Control preconfluent and confluent cells in room air contained 196 +/- 18 ng Cu,Zn-SOD/10(6) cells. A23187 (0.33 microM), forskolin (10 microM), isobutylmethylxanthine (0.1 mM), dexamethasone (1 microM), triiodothyronine (1 microM) and retinoic acid (1 microM) failed to alter this level of Cu,Zn-SOD. Exposure to anoxia and hyperoxia both elevated the level approximately 1.5-2.0-fold over 20% oxygen-exposed controls at 48-72 hr. Similarly, exposures to glucose oxidase (0.0075 units/ml), menadione (12.5 microM), xanthine-xanthine oxidase (10 microM, 0.03 units/ml) and H2O2 (0.0005%) increased the level up to two-threefold over controls at 24-48 hr. Lipopolysaccharide, TGF beta 1, TNF alpha, and Il-1 also increased levels of cellular Cu,Zn-SOD, but only in proliferating cells. Il-2, Il-4, interferon-gamma, and GM-CSF had no effect on Cu,Zn-SOD. All treatments that elevated SOD resulted in inhibition of cellular growth, but decreased growth of cells at confluence alone was not associated with increased Cu,Zn-SOD. We propose from these studies that Cu,Zn-SOD of endothelial cells is not under conventional second messenger or hormonal regulation, but that up-regulation of the enzyme is associated with (and perhaps stimulated by) free-radical or oxidant production that also may be influenced by availability of certain cytokines under replicating conditions.
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PMID:Regulation of Cu,Zn-superoxide dismutase in bovine pulmonary artery endothelial cells. 133 80

In the subjects being prepared to neurosurgical treatment an i.v. injection of NaHCO3 (2 mEq/kg) elicited a significant increase in PCSFO2 from 69 +/- 6.4 (SEM) Torr to 75.5 +/- 3.9 (SEM) Torr. This change ws accompanied by a significant drop of PaO2 from 150.5 +/- 6.0 Torr to 138.0 +/- 5.8 Torr. Metabolic alkalosis (pH 7.54 +/- 0.02 SEM) elicited by bicarbonate administration was accompanied by arterial blood hyperoxia. Both these factors reduce the cerebral flow (CBF). We suppose that changes in the blood--CSF oxygen relationship reflect the presence of a mechanism which might protect the CNS against a decrease in CBF.
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PMID:Decrease of oxygen difference between arterial blood and cerebrospinal fluid after intravenous injection of sodium bicarbonate in hyperoxic patients, anaesthetized, paralyzed and artificially ventilated. 627 42

In order to elucidate that which are the factors that may influence the direction of brain activation-induced changes in the redox state of oxidized/reduced nicotinamide adenine dinucleotide (NAD/NADH), the brain cortex was electrically stimulated during arterial hypotension and following reinfusion of the shed blood, during arterial hyper- and hypoxia, and during the second phase of spreading cortical depression (SD). Cerebrocortical NADH fluorescence and vascular volume ( CVV ) of cats, anaesthetized by chloralose, were measured with a microscope fluororeflectometer . Under physiologically normal conditions electrical stimulation resulted in pronounced cortical NAD reduction and increase in CVV . These reactions were not altered by arterial hyperoxia and continuous superfusion of the brain cortex with oxygenated artificial cerebrospinal fluid (mock CSF). Arterial hypotension and SD (in phase II) increased NAD reduction and CVV markedly, and the superimposed electrical stimulation brought about NADH oxidation and greatly depressed CVV responses. Reinfusion of the shed blood did not restore NAD/NADH redox state and CVV to their reference levels, and electrical stimulation under this condition led to NADH oxidation and negligible vascular reactions. Since under physiologically normal conditions electrical activation of the brain cortex resulted in NAD reduction and marked increase in CVV and the magnitude of these reactions were not altered by arterial hyperoxia or by superfusion of the brain cortex with oxygenated CSF, it is very unlikely that the brain cortex became hypoxic during stimulation. Because when the steady NAD/NADH redox state of the brain cortex was shifted toward reduction by arterial hypotension and reinfusion and SD, electrical stimulation led to NADH oxidation, it is suggested that the prestimulatory steady redox state has great importance in determining the direction of NAD/NADH redox reactions evoked by activation of the brain cortex.
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PMID:Determinants of brain activation-induced cortical NAD/NADH responses in vivo. 632 66

If 100% O2 produces hyperventilation by increasing central CO2 due to cerebral vasoconstriction or dimished reduction of oxyhemoglobin, then, there should be a parallel decrease in alveolar and CSF PCO2 during O2 breathing in neonates. To test this hypothesis, we measured ventilation, alveolar PCO2 and CSF PCO2, pH and HCO2 before and 10-20 min after infants began breathing 100% O2. With 100% O2, minute ventilation increased from 0.193 +/- (SE) 0.013 (n = 7) to 0.252 +/- 0.013 liter/min/kg (p less than 0.015), PACO2 decreased from 42 +/- 2 to 38 +/- 2 mm Hg (p less than 0.005), CSF PCO2 decreased from 51 +/- 1 to 44 +/- 1 mm Hg (p less than 0.015), and pH increased from 7.308 +/- 0.013 to 7.354 +/- 0.013 (p less than 0.05). CSF bicarbonate decreased, but not significantly. These findings, showing a trend toward alkalosis, suggest that the neonate, like the adult man, induces hyperventilation during hyperoxia via an increase in PCO2 at the central level.
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PMID:Effect of inhaling 100% O2 on ventilation and acid-base balance in cerebrospinal fluid of neonates. 677 Sep 13

We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.
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PMID:Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats. 880 15

The present study was designed to determine if hyperoxia elicits pial artery vasoconstriction and to characterize the contribution of endothelin-1 (ET-1) to that vascular response in newborn pigs equipped with a closed cranial window. Hyperoxic conditions were established by ventilating the piglets with 100% O(2) during normocapnia and concomitantly topically applying artificial CSF that had been bubbled with 100% O(2). Hyperoxia elevated CSF ET-1 from 23+/-1 to 45+/-4 pg/ml. Hyperoxia also elicited pial artery vasoconstriction that was attenuated by BQ123 (10(-6) M), an ET-1 antagonist (-15+/-1 vs. -5+/-1%). These data indicate that ET-1 contributes to hyperoxic pial artery vasoconstriction.
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PMID:Endothelin-1 contributes to normocapnic hyperoxic pial artery vasoconstriction. 1052 21

Granulocyte macrophage-colony stimulating factor (GM-CSF) plays an important role in pulmonary homeostasis, with effects on both alveolar macrophages and alveolar epithelial cells. We hypothesized that overexpression of GM-CSF in the lung would protect mice from hyperoxic lung injury by limiting alveolar epithelial cell injury. Wild-type C57BL/6 mice and mutant mice in which GM-CSF was overexpressed in the lung under control of the SP-C promoter (SP-C-GM mice) were placed in >95% oxygen. Within 6 days, 100% of the wild-type mice had died, while 70% of the SP-C-GM mice remained alive after 10 days in hyperoxia. Histological assessment of the lungs at day 4 revealed less disruption of the alveolar wall in SP-C-GM mice compared to wild-type mice. The concentration of albumin in bronchoalveolar lavage fluid after 4 days in hyperoxia was significantly lower in SP-C-GM mice than in wild-type mice, indicating preservation of alveolar epithelial barrier properties in the SP-C-GM mice. Alveolar fluid clearance was preserved in SP-C-GM mice in hyperoxia, but decreased significantly in hyperoxia-exposed wild-type mice. Staining of lung tissue for caspase 3 demonstrated increased apoptosis in alveolar wall cells in wild-type mice in hyperoxia compared to mice in room air. In contrast, SP-C-GM mice exposed to hyperoxia demonstrated only modest increase in alveolar wall apoptosis compared to room air. Systemic treatment with GM-CSF (9 micro g/kg/day) during 4 days of hyperoxic exposure resulted in decreased apoptosis in the lungs compared to placebo. In studies using isolated murine type II alveolar epithelial cells, treatment with GM-CSF greatly reduced apoptosis in response to suspension culture. In conclusion, overexpression of GM-CSF enhances survival of mice in hyperoxia; this effect may be explained by preservation of alveolar epithelial barrier function and fluid clearance, at least in part because of reduction in hyperoxia-induced apoptosis of cells in the alveolar wall.
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PMID:Transgenic overexpression of granulocyte macrophage-colony stimulating factor in the lung prevents hyperoxic lung injury. 1463 11

Cytokines are peptides that are produced by virtually every nucleated cell type in the body, possess overlapping biological activities, exert different effects at different concentrations, can either synergize or antagonize the effects of other cytokines, are regulated in a complex manner, and function via cytokine cascades. Hyperoxia-induced acute lung injury (HALI) is characterized by an influx of inflammatory cells, increased pulmonary permeability, and endothelial and epithelial cell injury/death. Some of these effects are orchestrated by cytokines. There are significant differences in the response of the developing versus the adult lung to hyperoxia. We review here cytokines (and select growth factors) that are involved in tolerance toward HALI in animal models. Increased cytokine expression and release have a cascade effect in HALI. IL-1 precedes the increase in IL-6 and CINC-1/IL-8 and this seems to predate the influx of inflammatory cells. Inflammatory cells in the alveolar space amplify the lung damage. Other cytokines that are primarily involved in this inflammatory response include IFN-gamma, MCP-1, and MIP-2. Certain cytokines (and growth factors) seem to ameliorate HALI by affecting cell death pathways. These include GM-CSF, KGF, IL-11, IL-13, and VEGF. There are significant differences in the type and temporal sequence of cytokine expression and release in the adult and newborn lung in response to hyperoxia. The newborn lung is greatly resistant to hyperoxia compared to the adult. The delayed increase in lung IL-1 and IL-6 in the newborn could induce protective factors that would help in the resolution of hyperoxia-induced injury. Designing a therapeutic approach to counteract oxygen toxicity in the adult and immature lung first needs understanding of the unique responses in each scenario.
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PMID:Cytokines in tolerance to hyperoxia-induced injury in the developing and adult lung. 1678 48

We have previously demonstrated that mice exposed to sublethal hyperoxia (an atmosphere of >95% oxygen for 4 days, followed by return to room air) have significantly impaired pulmonary innate immune response. Alveolar macrophages (AM) from hyperoxia-exposed mice exhibit significantly diminished antimicrobial activity and markedly reduced production of inflammatory cytokines in response to stimulation with LPS compared with AM from control mice in normoxia. As a consequence of these defects, mice exposed to sublethal hyperoxia are more susceptible to lethal pneumonia with Klebsiella pneumoniae than control mice. Granulocyte/macrophage colony-stimulating factor (GM-CSF) is a growth factor produced by normal pulmonary alveolar epithelial cells that is critically involved in maintenance of normal AM function. We now report that sublethal hyperoxia in vivo leads to greatly reduced alveolar epithelial cell GM-CSF expression. Systemic treatment of mice with recombinant murine GM-CSF during hyperoxia exposure preserved AM function, as indicated by cell surface Toll-like receptor 4 expression and by inflammatory cytokine secretion following stimulation with LPS ex vivo. Treatment of hyperoxic mice with GM-CSF significantly reduced lung bacterial burden following intratracheal inoculation with K. pneumoniae, returning lung bacterial colony-forming units to the level of normoxic controls. These data point to a critical role for continuous GM-CSF activity in the lung in maintenance of normal AM function and demonstrate that lung injury due to hyperoxic stress results in significant impairment in pulmonary innate immunity through suppression of alveolar epithelial cell GM-CSF expression.
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PMID:GM-CSF and the impaired pulmonary innate immune response following hyperoxic stress. 1689 99


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