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

In the ventilated ischemic lung, oxygen tension will increase at a time when glucose depletion may impair antioxidant defenses, thereby predisposing the lung to injury mediated by oxygen radicals. In the unventilated ischemic lung, however, glucose depletion in the setting of low oxygen tension may decrease production of ATP, leading to injury by a different mechanism. In this study, we evaluated the role of both oxygen tension and glucose concentration on ischemic injury in isolated ferret lungs. Injury, defined as an increase in vascular permeability, was assessed by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb) after 3 h of normothermic (37 degrees C) ischemia without reperfusion. Lungs were ventilated with either 95% O2-5% CO2 or 0% O2-5% CO2. The vasculature was flushed with physiological salt solution containing either 15 mM glucose (hyperoxia-glucose, anoxia-glucose), 15 mM sucrose (hyperoxia-sucrose, anoxia-sucrose), or no substrate (hyperoxia-no substrate, anoxia-no substrate) (n = 6 for each condition). Kf and sigma alb in hyperoxia-no substrate group did not differ from values in minimally ischemic normoxic normoglycemic ferret lungs. Without glucose, ischemic injury was worse in anoxic than in hyperoxic lungs. With glucose, ischemic injury was worse in hyperoxic than in anoxic lungs. Glucose exacerbated injury in hyperoxic, but not anoxic, lungs. These results indicate that ischemic injury in these lungs depended on both oxygen tension and glucose concentration and suggest that both oxygen radical generation and ATP depletion during ischemia may contribute to the development of this injury.
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PMID:Effects of oxygen tension and glucose concentration on ischemic injury in ventilated ferret lungs. 822 35

The aim of the present study was to examine the effect of exposing animals to 100% oxygen instead of room air on renal function and endogenous antioxidant enzymes of the postischemic reperfused rat kidney. Superoxide dismutase (SOD), catalase and glutathione peroxidase (GPX) were determined in the homogenate of the left kidney after 45 min of ischemia, caused by clamping the left renal artery, 10 and 90 min after reperfusion while the animals breathed room air or 100% O2. The right kidney served as a control. The possible influence of trapped blood in the clamped kidney was also investigated by the use of a correction factor based on the Hb concentration in the homogenate. The results indicate that such correction is necessary as the blood adds significant antioxidant activity. The activities of all 3 enzymes after 45 min of ischemia decreased significantly in the left (ischemic) compared to the right (control) kidney, to 64% of the control levels for catalase, 58% for SOD and 49% for GPX. After 10 min of reflow, a further decrease in the activities of catalase (to 49%) and of GPX (to 29%) was found. SOD activity, however, increased to 64%. After 90 min of reperfusion, restoration toward normal levels was noticed (SOD activity increased to 70%, catalase to 76% and GPX to 58%). Breathing 100% O2 resulted in a significant decrease in all enzyme activities (to 38.6% for catalase, 45% for SOD and to 27.4% for GPX). This inactivation can be explained by increased reactive oxygen species (ROS) activity during hyperoxia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of oxygen tension on activity of antioxidant enzymes and on renal function of the postischemic reperfused rat kidney. 845 Sep 13

Changes in O2 tension such as those associated with hypoxic ischemia or hyperoxia may potentially modulate purine nucleotide turnover and production of associated catabolites. We used an isolated perfused rat lung preparation to evaluate the effect of O2 tension on pulmonary uric acid production. Three O2 concentrations (21%, normoxia; 95%, hyperoxia; 0%, hypoxia) were utilized for both pulmonary ventilation and equilibration of recirculating perfusate. All gas mixtures contained 5% CO2 and were balanced with N2. We used Certified Virus Free Sprague-Dawley male rats weighting 250-300 g, four to five rats in each exposure regimen. After a 10-min equilibration period, we measured uric acid levels at 0 and 60 min in lung perfusate and at 60 min in lung tissue. After 60 min of ventilation/perfusion, we observed significant uric acid accumulation in both lung tissue (25-60%) and perfusate (8- to 10-fold) for all three O2 regimens. However, hypoxia produced substantially greater net uric acid concentrations (net = the difference between zero and 60 min) than either normoxia or hyperoxia (1.5-fold in lung tissue, and 2-fold in perfusate, respectively). The data suggest that pulmonary hypoxia results in greater purine catabolism leading to increased uric acid production. Vascular space uric acid, as measured in the recirculating perfusate, was proportional to lung weight changes (r = 0.99) with hypoxia exhibiting the greatest values, possibly reflecting a linkage between tissue perturbation and uric acid release. Thus, measurement of uric acid may serve as a useful marker of adenine nucleotide turnover and lung injury.
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PMID:Measurement of uric acid as a marker of oxygen tension in the lung. 847 Sep 1

In order to evaluate the relationship between brain oxygen supply and demand (O2 balance) in real time, it is necessary to use a multiparametric monitoring approach. Cerebral blood flow (CBF) is a representative parameter of O2 supply. The extracellular level of K+ is a reliable indicator of O2 demand since more than 60% of the energy consumed by the brain is utilized by active transport processes. Mitochondrial NADH redox state can represent the balance between O2 supply and demand. In order to monitor the brain of experimental animals or patients, we constructed the multiparametric assembly (MPA) and the following parameters were monitored simultaneously and in real time: CBF, CBV, NADH redox state, extracellular K+, DC potential, EEG, tissue temperature and ICP. Animals were exposed to hypoxia, ischemia, hypercapnia, hyperoxia and spreading depression (SD) and the relative changes in CBF and NADH were calculated and found to be significant indicators of brain energy state. Monitoring these two parameters increases the possibility of differentiating between various pathophysiological states. Each added parameter increases the power of diagnosis and determination of the functional state of the brain. Preliminary results obtained in patients monitored in the ICU or in the OR show that the responses to hypercapnia, spreading depression or ischemia are similar to those measured in experimental animals.
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PMID:Multiparametric monitoring of brain oxygen balance under experimental and clinical conditions. 958 30

Endothelial cell association with vascular basement membranes is complex and plays a critical role in regulation of cell adhesion and proliferation. The interaction between the membrane-associated 67-kd receptor (67LR) and the basement membrane protein laminin has been studied in several cell systems where it was shown to be crucial for adhesion and attachment during angiogenesis. As angiogenesis in the pathological setting of proliferative retinopathy is a major cause of blindness in the Western world we examined the expression of 67LR in a murine model of hyperoxia-induced retinopathy that exhibits retinal neovascularization. Mice exposed to hyperoxia for 5 days starting at postnatal day 7 (P7) and returned to room air (at P12) showed closure of the central retinal vasculature. In response to the ensuing retinal ischemia, there was consistent preretinal neovascularization starting around P17, which persisted until P21, after which the new vessels regressed. Immunohistochemistry was performed on these retinas using an antibody specific for 67LR. At P12, immunoreactivity for 67LR was absent in the retina, but by P17 it was observed in preretinal proliferating vessels and also within the adjacent intraretinal vasculature. Intraretinal 67LR immunoreactivity diminished beyond P17 until by P21 immunoreactivity was almost completely absent, although it persisted in the preretinal vasculature. Control P17 mice (not exposed to hyperoxia) failed to demonstrate any 67LR immunoreactivity in their retinas. Parallel in situ hybridization studies demonstrated 67LR gene expression in the retinal ganglion cells of control and hyperoxia-exposed mice. In addition, the neovascular intra- and preretinal vessels of hyperoxia-treated P17 and P21 mice labeled strongly for 67LR mRNA. This study has characterized 67LR immunolocalization and gene expression in a murine model of ischemic retinopathy. Results suggest that, although the 67LR gene is expressed at high levels in the retinal ganglion cells, the mature receptor protein is preferentially localized to the proliferating retinal vasculature and is almost completely absent from quiescent vessels. The differential expression of 67LR between proliferating and quiescent retinal vessels suggests that this laminin receptor is an important and novel target for future chemotherapeutic intervention during proliferative vasculopathies.
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PMID:The 67-kd laminin receptor is preferentially expressed by proliferating retinal vessels in a murine model of ischemic retinopathy. 958 4

Hyperoxia and ischemia-reperfusion cause profound lung cellular damage mediated, in part, by generation of oxygen radicals. We hypothesized that gene therapy can be used to overcome oxidant injury by augmenting intracellular antioxidant enzymes. Adult rats were injected intratracheally with an adenovirus (Ad) vector encoding human superoxide dismutase (CuZn-SOD) or catalase cDNA, a mixture of both Ad vectors, or a control Ad vector containing no exogenous gene. Expression of human catalase and CuZn-SOD was demonstrated 3 days later in distal lung epithelial cells and alveolar macrophages, using ELISA and immunochemistry. After exposure to 100% O2 for 62 hr, survival was greater in rats injected with the catalase and/or SOD Ad vectors than in control rats. Ischemia-reperfusion injury was evaluated in the isolated perfused lung model. Overexpression of SOD worsened ischemia-reperfusion injury. Interestingly, concomitant overexpression of catalase prevented this adverse effect, but did not protect against ischemia-reperfusion injury. We conclude that Ad-mediated transfer to lungs of both catalase and SOD cDNAs protects from pulmonary O2 toxicity. Absence of protection against ischemia-reperfusion using intratracheal Ad injections may be related to the lack of endothelial protection, despite epithelial expression of catalase and SOD.
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PMID:Gene therapy for oxidant injury-related diseases: adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury. 968 20

Melatonin was recently reported to be an effective free radical scavenger and antioxidant. Melatonin is believed to scavenge the highly toxic hydroxyl radical, the peroxynitrite anion, and possibly the peroxyl radical. Also, secondarily, it reportedly scavenges the superoxide anion radical and it quenches singlet oxygen. Additionally, it stimulates mRNA levels for superoxide dismutase and the activities of glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase (all of which are antioxidative enzymes), thereby increasing its antioxidative capacity. Also, melatonin, at least at some sites, inhibits nitric oxide synthase, a pro-oxidative enzyme. In both in vivo and in vitro experiments melatonin has been shown to reduce lipid peroxidation and oxidative damage to nuclear DNA. While these effects have been observed primarily using pharmacological doses of melatonin, in a small number of experiments melatonin has been found to be physiologically relevant as an antioxidant as well. The efficacy of melatonin in inhibiting oxidative damage has been tested in a variety of neurological disease models where free radicals have been implicated as being in part causative of the condition. Thus, melatonin has been shown prophylactically to reduce amyloid beta protein toxicity of Alzheimer's disease, to reduce oxidative damage in several models of Parkinson's disease (dopamine auto-oxidation, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine), to protect against glutamate excitotoxicity, to reduce ischemia-reperfusion injury, to lower neural damage due to gamma-aminolevulinic acid (phorphyria), hyperbaric hyperoxia and a variety of neural toxins. Since endogenous melatonin levels fal 1 markedly in advanced age, the implication of these findings is that the loss of this antioxidant may contribute to the incidence or severity of some age-associated neurodegenerative diseases.
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PMID:Oxidative damage in the central nervous system: protection by melatonin. 977 Feb 44

Reactive oxygen species (ROS) have been implicated in the pathogenesis of many clinical disorders such as adult respiratory distress syndrome, ischemia-reperfusion injury, atherosclerosis, neurodegenerative diseases, and cancer. Genetically engineered animal models have been used as a tool for understanding the function of various antioxidant enzymes in cellular defense mechanisms against various types of oxidant tissue injury. Transgenic mice overexpressing three isoforms of superoxide dismutase, catalase, and the cellular glutathione peroxidase (GSHPx-1) in various tissues show an increased tolerance to ischemia-reperfusion heart and brain injury, hyperoxia, cold-induced brain edema, adriamycin, and paraquat toxicity. These results have provided for the first time direct evidence demonstrating the importance of each of these antioxidant enzymes in protecting the animals against the injury resulting from these insults, as well as the effect of an enhanced level of antioxidant in ameliorating the oxidant tissue injury. To evaluate further the nature of these enzymes in antioxidant defense, gene knockout mice deficient in copper-zinc superoxide dismutase (CuZnSOD) and GSHPx-1 have also been generated in our laboratory. These mice developed normally and showed no marked pathologic changes under normal physiologic conditions. In addition, a deficiency in these genes had no effects on animal survival under hyperoxida. However, these knockout mice exhibited a pronounced susceptibility to paraquat toxicity and myocardial ischemia-reperfusion injury. Furthermore, female mice lacking CuZnSOD also displayed a marked increase in postimplantation embryonic lethality. These animals should provide a useful model for uncovering the identity of ROS that participate in the pathogenesis of various clinical disorders and for defining the role of each antioxidant enzyme in cellular defense against oxidant-mediated tissue injury.
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PMID:The nature of antioxidant defense mechanisms: a lesson from transgenic studies. 978 1

Nitroxide stable free radicals have previously been found to afford protection in various biological systems against diverse types of oxidative stress, including, ischemia/reperfusion, hyperoxia, mechanical trauma, toxic xenobiotics, ionizing radiation, gastric and colonic irritants or strong oxidants. Dismutation of superoxide has originally been suggested to be one of the mechanisms that underlie the anti-oxidant effect of nitroxides. However, no direct evidence has been found, so far, to support this assumption. In the present study, superoxide and H2O2, generated enzymatically, were used to directly inactivate papain, a sulfhydryl enzyme, in vitro. The rate of papain inactivation served to assess the damage. The reaction mixtures contained a chelate in order to prevent the effect of adventitious redox-active metal ions, pre-empt the Fenton reaction and avoid hydroxyl-induced damage. Catalase or SOD alone partially protected the papain from inactivation. The protective effect of nitroxides resembled that of SOD in several aspects: a) nitroxides provided partial protection; b) the protective effect of nitroxides did not increase with the elevation of their concentration (above 0.5 mM); c) the combined addition of SOD and the nitroxide did not provide greater protection than that demonstrated by nitroxides or SOD separately; d) the effects of catalase with the nitroxide were additive; e) the nitroxide, like SOD itself, did not protect papain from H2O2-induced inactivation; f) the nitroxide was found not to be consumed in the course of the reaction but rather to be recycled. The results indicate that: (a) the main species responsible for the papain inactivation in a system in which the effect of transition metals is pre-empted, are O2-. and H2O2; (b) nitroxides inhibit the oxidative damage by removing superoxide not stoichiometrically, but rather catalytically as SOD-mimics; (c) nitroxides do not afford protection when the oxidative damage is induced directly by H2O2 (and not mediated by redox-active metals).
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PMID:An SOD-mimicry mechanism underlies the role of nitroxides in protecting papain from oxidative inactivation. 982 49

Several surgical approaches are being used to induce myocardial ischemia in rats. The present study investigated two different operative procedures in spontaneously breathing and mechanically ventilated rats under sham conditions. A snare around the left coronary artery (LCA) was achieved without occlusion. Left lateral thoracotomy was performed in spontaneously breathing and mechanically ventilated rats (tidal volume 8 ml/kg) with a respiratory rate of 90 strokes/min at different levels of O2 supplementation (room air and 30, 40, and 90% O2). All animals were observed for 60 min after thoracotomy. Rats operated with exteriorization of the heart through left lateral thoracotomy while breathing spontaneously developed severe hypoxia and hypercapnia despite an intrathoracic operation time of <1 min. Arterial O2 content decreased from 18.7 +/- 0.5 to 3.3 +/- 0.9 vol%. Lactate increased from 1.2 +/- 0.1 to 5.2 +/- 0.3 mmol/l. Significant signs of ischemia were seen in the electrocardiogram up to 60 min. Mechanically ventilated animals exhibited a spectrum ranging from hypoxia (room air) to hyperoxia (90% O2). In order not to jeopardize findings in experimental myocardial ischemia-reperfusion injury models, stable physiological parameters can be achieved in mechanically ventilated rats at an O2 application of 30-40% at 90 strokes/min.
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PMID:Surgical procedure affects physiological parameters in rat myocardial ischemia: need for mechanical ventilation. 995 Aug 47


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