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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It is now becoming increasingly clear that free radicals contribute to brain damage in several conditions, such as hyperoxia and trauma. It has been more difficult to prove that free radical production mediates ischemic brain damage, but it has often been suggested that it may be a major contributor to reperfusion damage, observed following transient ischemia. Recent results demonstrate that cerebral ischemia of long duration, particularly when followed by reperfusion, leads to enhanced production of partially reduced oxygen species, notably hydrogen peroxide (H2O2). It has also been suggested that postischemic hyperoxia, e.g. an increased oxygen tension during the recirculation period, adversely affects recovery following transient ischemia. Other data support the notion that brain damage caused by permanent ischemia (stroke) is significantly influenced by production of free radicals. The present study, however, fails to show that recirculation following brief periods of ischemia (15 min) leads to an enhanced H2O2 production, and that hyperoxia aggravates the ischemic damage. This study was undertaken to reveal whether variations in oxygen supply in the postischemic period following forebrain ischemia in rats affect free radical production and the brain damage incurred. To that end, rats ventilated on N2O/O2 (70:30) were subjected to 15 min of transient ischemia. Normoxic animals were ventilated with the N2O/O2 mixture, hyperoxic animals with 100% O2, and hypoxic ones with about 10% O2 (balance either N2O/N2 or N2) during the recirculation. At the end of this period, the animals were decapitated for assessment of H2O2 production with the aminotriazole/catalase method. This method is based on the notion that aminotriazole interacts with H2O2 to inactivate catalase; thus, the rate of inactivation of catalase in aminotriazole treated animals reflects H2O2 production. In a parallel series, animals ventilated with one of the three gas mixtures in the early recirculation period, respectively, were allowed to recover for 7 days, with subsequent perfusion-fixation of brain tissues and light microscopical evaluation of the brain damage. Animals given aminotriazole, whether rendered ischemic or not, showed a reduced tissue catalase activity, reflecting H2O2 production in the brain. Hyperoxic animals failed to show increased tissue H2O2 production, while hypoxic ones showed a tendency towards decreased production. However, all three groups (hypo, normo- and hyperoxic) had similar density and distribution of neuronal damage. These results suggest that although postischemic oxygen tensions may determine the rates of H2O2 production, variations in oxygen tensions do not influence the final brain damage incurred.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Free radical production and ischemic brain damage: influence of postischemic oxygen tension. 205 15

Free radicals have been incriminated in a variety of injurious processes including the toxicity of the herbicide paraquat and the damage following ischemia and reperfusion of different organs. Based on the assumption that iron and copper could serve as mediators for the transformation of relatively low reactive species (such as superoxide radicals, hydrogen peroxide, ascorbate, and others) to the highly reactive species, in the site-specific metal-mediated mechanism, two new modes for intervention have been tried out. The first is the introduction of specific chelators that "pull" out redox-active and available metals, and by this reduce the apparent damage. Desferrioxamine was shown to protect bacterial cells and mammals against the poisonous effects of paraquat. Using the retrogradly perfused isolated rat heart, we have demonstrated that the chelator neocuproine, which effectively binds both iron and copper provides a major protection against hydrogen peroxide-induced cardiac damage and against ischemia/reperfusion-induced arrhythmias. Likewise, TPEN a heavy metal chelator, provides almost total (greater than 90%) protection against ischemia/reperfusion-induced arrhythmias. The other mode of intervention is the use of redox-inactive metal ions that could compete for the binding sites of iron and copper, and by this "push" these metal ions out, lead to their displacement, and divert the site of free radical attack. Applying Zn(II) complexes provided a marked protection against metal mediated free radical-induced damage in the copper-mediated paraquat toxicity to E. coli, and in the arrhythmias induced by ischemia and reperfusion. It is proposed that the complex zinc-desferrioxamine would be the ultimate protector being effective by both the "pull" and "push" mechanisms.
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PMID:Protection against free radical-induced and transition metal-mediated damage: the use of "pull" and "push" mechanisms. 206 Aug 41

Oxygenated free-radicals appear to play a prominent role in mediating damage associated with gastrointestinal diseases. Production of reactive oxygen metabolites in ischemia-reperfusion involves oxidases found in resident phagocytic cells and microvascular and mucosal epithelial cells. Platelet activating factor (PAF), a phospholipid associated with inflammatory disorders, has been shown to both prime and amplify the release of superoxide anion and hydrogen peroxide from polymorphonuclear neutrophils and macrophages stimulated by FMLP or PMA. To further elucidate the involvement of free radicals in intestinal damage and the potential role of PAF in their production, we examined the effect of superoxide dismutase (SOD) and BN 52021 (ginkgolide B) on ischemia-reperfusion induced damage in the small intestine. The study involved 32 Sprague-Dawley rats (100-200 g) divided into four groups. Three of these groups were subjected to occlusion of the mesenteric artery 30 mins followed by 24 h reperfusion. On 2 groups SOD (15,000 U/kg/iv) and BN 52021 (20 mg/kg/po) were administered 45 mins before arterial occlusion. Following the 24 h reperfusion, the rats were sacrificed after overnight fasting. The jejunum and ileon were removed and fixed for morphological examination. Lesions in the small intestine were quantified. The results showed extensive necrosis, hemorrhage, oedema and neutrophil invasion in the jejunal and ileal mucosa. This injury was significantly reduced by SOD (15,000 U/kg/iv) and BN 52021 (20 mg/kg/po) pretreatment. In conclusion, free-oxygenated radicals appear to mediate reperfusion damage in the small intestine and PAF appears to be involved in the genesis of these toxic products. Thus, SOD and BN 52021 may be considered as protectors against ischemic disorders.
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PMID:Superoxide dismutase (SOD) and the PAF-antagonist (BN 52021) reduce small intestinal damage induced by ischemia-reperfusion. 206 Aug 44

We hypothesized that xanthine oxidase (XO)-derived hydrogen peroxide (H2O2) contributes to ischemic skeletal muscle injury during reperfusion. We found that after ischemia (3 h) and then reperfusion (4 h) rat gastrocnemius muscles had decreased contractile function following direct stimulation. Three lines of investigation suggested that XO-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. First, treatment with dimethylthiurea (DMTU), a highly permeant O2 metabolite scavenger, but not urea, just before reperfusion improved muscle function in legs subjected to ischemia and then reperfusion. Second, gastrocnemius muscles from rats fed tungsten or allopurinol had negligible XO activities and increased muscle function after ischemia and reperfusion. Third, as assessed by measurement of skeletal muscle catalase activity in the presence of aminotriazole, H2O2 was measured during reperfusion of ischemic muscles from untreated or urea-treated rats but not during reperfusion of muscles from rats treated with DMTU, tungsten, or allopurinol.
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PMID:Xanthine oxidase-derived H2O2 contributes to reperfusion injury of ischemic skeletal muscle. 211 Jul 80

1. The aim of this study was to examine the rapid changes in extracellular hydrogen ion activity [( H+]o or pHo) which are associated with depolarization and repolarization subsequent to cerebral ischemia reperfusion. Two parallel studies were performed with different rat models of ischemia: repetitive severe ischemia produced in anesthetized animals by occlusion of the vertebral and carotid arteries and temporary interruption of blood flow in isolated brain. [H+]o and direct current potential (DC potential) were recorded simultaneously in all experiments. Examination of these two parameters was supplemented by recording tissue concentration of carbon dioxide (PtCO2) in the four-vessel occlusion model and assaying major metabolites involved in energy production in experiments with isolated brains. 2. Measurements of [H+]o during ischemia consistently revealed a steady increase of [H+]o on which was superimposed an abrupt and transient fall in [H+]o closely related to the occurrence of the fast negative shift of DC potential characterizing brain-cell depolarization. Analysis of the relationship between the magnitude of the transient fall in H+ and the level of [H+]o at which this occurred showed that the amplitude of the transient fall in H+ increased with tissue acidosis. 3. We propose that this phenomenon is indirect evidence that rapid transfer of acid equivalents occurs across the plasmalemma, concomitantly to its depolarization. Both events probably result from a common cause, i.e., nonspecific increase of the cell-membrane permeability to ions subsequent to opening of membrane channels. 4. Early on during recirculation, an acidotic [H+]o shift associated with membrane repolarization was clearly visible whenever the ionic gradients recovered rapidly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A rapid redistribution of hydrogen ions is associated with depolarization and repolarization subsequent to cerebral ischemia reperfusion. 212 59

In order to assess tissue blood flow quantitatively under various temperature conditions, we have developed a new blood-flow measurement apparatus based on the thermal diffusion method. This new method is hardly affected by environmental temperature, by means of using the thermal clearance curve with its baseline corrected before each measurement. Fundamental studies concerning the measurement of human skin blood flow were carried out in the finger. The results obtained were as follows. 1) The gradient of the thermal clearance curve did not show significant changes under various temperature conditions. This result indicated that the effects of environmental temperature on the thermal clearance curve were almost removed. 2) A highly positive correlation was obtained between the thermal conductivity of various materials similar to human skin in thermal conductivity and the gradient of the thermal clearance curve from a probe placed on a plate of each material. 3) There was linear relationship between the water flow and the gradient of the thermal clearance curve in various water flows of a micro-circulation model. The gradient of the thermal clearance curve obtained for each water flow had good reproducibility. 4) The gradient of the thermal clearance curve changed in parallel with the finger ischemia and hyperemia induced by inflation of a tourniquet. There was good reproducibility in continuous measurements. 5) A highly significant positive correlation was obtained between finger blood flow measured by the inhaled hydrogen clearance method and the gradient of the thermal clearance curve, indicating that it was possible to assess finger blood flow quantitatively by the gradient of the thermal clearance curve. The weak point in the former thermal diffusion method, where the baseline was unstable as a result of environmental temperature, was removed. It was concluded that this new thermal diffusion method using the thermal clearance curve, which was calibrated previously by the hydrogen clearance method, enabled us to measure finger blood flow noninvasively at various temperatures. This method will be useful for diagnosis and research in various medical fields.
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PMID:[Development of an improved system for monitoring the peripheral circulation and its application. Part 1. Fundamental study]. 214 53

The objective of this study was to determine whether hydrogen peroxide, iron, and/or hydroxyl radicals play a role in ischemia/reperfusion (I/R)-induced granulocyte infiltration in the feline small intestine and whether a chemoattractant is formed when superoxide or hydrogen peroxide reacts with feline extracellular fluid. In vivo determinations of granulocyte infiltration consisted of measurements of tissue myeloperoxidase activity in either the intestinal mucosa (I/R studies) or dermis (chemotaxis studies), whereas in vitro measurements of granulocyte migration were obtained using a Boyden chamber. Treatment with either catalase or the iron chelator deferoxamine significantly attenuated granulocyte infiltration into the mucosa induced by reperfusion of the ischemic intestine. Two hydroxyl radical scavengers, dimethyl sulfoxide (DMSO) and dimethylthiourea (DMTU), were also evaluated for their ability to modulate I/R-induced granulocyte infiltration. DMTU significantly attenuated the I/R-induced granulocyte accumulation, whereas DMSO had no effect. In other experiments, we were unable to stimulate granulocyte migration with feline plasma exposed to superoxide-generating systems using both in vitro and in vivo models of leukocyte chemotaxis. However, hydrogen peroxide in the presence of either ferrous iron or hemoglobin did significantly increase the chemotactic activity of cat plasma. The results obtained from our studies suggest that either hydrogen peroxide or radical species derived from the interaction of superoxide and hydrogen peroxide with iron elicit I/R-induced granulocyte infiltration in the intestine.
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PMID:Role of oxidants in ischemia/reperfusion-induced granulocyte infiltration. 215 38

The effects of short-duration forebrain ischemia on cerebral metabolism in the rat have been studied using several nuclear magnetic resonance (NMR) techniques. In vivo phosphorus-31 (31P) NMR spectroscopy showed that the model produces rapid cerebral energy failure and acidosis. Reperfusion was accompanied by recovery of high-energy metabolites in about 30 minutes, with a slower recovery of pH. Proton (1H) NMR spectra of perchloric acid extracts of selected brain regions showed that levels of alanine and gamma-aminobutyric acid (GABA) were elevated and the level of glutamate was depressed immediately after the ischemic insult, returning to normal by 24 hours. The lactate level remained elevated for up to 7 days after ischemia, suggesting ongoing abnormal mitochondrial function. Postischemic cerebral glucose metabolism was monitored using carbon-13 (13C)-labelled glucose as an NMR probe. Glycolysis was impaired immediately after the ischemic insult, resulting in accumulation of glucose in the tissue and reduced formation of amino acids and tricarboxylic acid cycle intermediates. Glycolysis recovered by 1 hour, but underwent a secondary decrease at 24 hours, the time at which neuronal injury became manifest histologically and physiologically. Nuclear magnetic resonance imaging was used to follow the regional development of tissue injury in selectively vulnerable brain regions. Striatal changes were evident by 24 hours after reperfusion, increasing in intensity and accompanied by hippocampal changes by 48 hours, then becoming less pronounced by 72 hours. Histologic analysis of regional neuronal injury correlated well with the imaging results, establishing NMR imaging as a noninvasive method of visualizing the regional development of ischemic tissue injury.
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PMID:Experimental cerebral ischemia studied using nuclear magnetic resonance imaging and spectroscopy. 215 86

Reactive oxygen metabolites have been implicated in the pathogenesis of mucosal injury induced by ischemia-reperfusion in adult animals, with recent interest centering on the capacity of polymorphonuclear neutrophil-derived oxidants to mediate this injury. A role for oxidants has also been postulated in the etiology of neonatal necrotizing enterocolitis. Based on evidence that the intrinsic capacity of the neonatal piglet intestine to detoxify hydrogen peroxide (H2O2) is minimal relative to that of older piglets, we characterized the changes in mucosal permeability induced by luminal perfusion with H2O2 and hypochlorous acid at concentrations that can be produced physiologically by activated neutrophils (0.05 mmol/L, 0.1 mmol/L, and 0.5 mmol/L), in the distal ileum of 1-d- and 1-mo-old piglets. Mucosal permeability was quantitated by measurement of blood-to-lumen clearance of 51-labeled chromium EDTA. Luminal perfusion with either H2O2 (0.05 mmol/L and 0.1 mmol/L) or hypochlorous acid (0.1 mmol/L and 0.5 mmol/L) significantly increased mucosal permeability in newborn piglets but did not affect mucosal permeability in 1-mo-old animals. Perfusion with 0.5 mmol/L H2O2 significantly increased mucosal permeability over control values in both age groups, but injury in the newborn intestine was significantly greater than that observed in 1-mo-old animals. Thus, as predicted by the reduced intrinsic capacity of the mucosa of neonatal piglets to detoxify H2O2, the ileum of newborn piglets is more vulnerable to oxidant-induced mucosal injury than is the ileum of older animals.
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PMID:Oxidant-induced increases in mucosal permeability in developing piglets. 216 84

The reaction of xanthine and xanthine oxidase generates superoxide and hydrogen peroxide. In contrast to earlier works, recent spin trapping data (Kuppusamy, P., and Zweier, J.L. (1989) J. Biol. Chem. 264, 9880-9884) suggested that hydroxyl radical may also be a product of this reaction. Determining if hydroxyl radical results directly from the xanthine/xanthine oxidase reaction is important for 1) interpreting experimental data in which this reaction is used as a model of oxidant stress, and 2) understanding the pathogenesis of ischemia/reperfusion injury. Consequently, we evaluated the conditions required for hydroxyl radical generation during the oxidation of xanthine by xanthine oxidase. Following the addition of some, but not all, commercial preparations of xanthine oxidase to a mixture of xanthine, deferoxamine, and either 5,5-dimethyl-1-pyrroline-N-oxide or a combination of alpha-phenyl-N-tert-butyl-nitrone and dimethyl sulfoxide, hydroxyl radical-derived spin adducts were detected. With other preparations, no evidence of hydroxyl radical formation was noted. Xanthine oxidase preparations that generated hydroxyl radical had greater iron associated with them, suggesting that adventitious iron was a possible contributing factor. Consistent with this hypothesis, addition of H2O2, in the absence of xanthine, to "high iron" xanthine oxidase preparations generated hydroxyl radical. Substitution of a different iron chelator, diethylenetriaminepentaacetic acid for deferoxamine, or preincubation of high iron xanthine oxidase preparations with chelating resin, or overnight dialysis of the enzyme against deferoxamine decreased or eliminated hydroxyl radical generation without altering the rate of superoxide production. Therefore, hydroxyl radical does not appear to be a product of the oxidation of xanthine by xanthine oxidase. However, commercial xanthine oxidase preparations may contain adventitious iron bound to the enzyme, which can catalyze hydroxyl radical formation from hydrogen peroxide.
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PMID:Hydroxyl radical is not a product of the reaction of xanthine oxidase and xanthine. The confounding problem of adventitious iron bound to xanthine oxidase. 217 Mar 83


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