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

In cats air embolism of the brain was produced by injecting 0.6 ml blood foam into the innominate artery proximal to the origin of both common carotid arteries. Air embolism caused transient ischemia of the brain, reaching a maximum within 1 min after injection. Resolution of the air embolism began a few minutes later and was completed within 15 min in the center and within 30 min in the border zone of the main supplying arteries. During this phase tissue perfusion was inhomogenous with reduced flow rates in some areas and reactive hyperemia up to 300% in others. This resulted in venous hyperoxia and a decrease of arteriovenous oxygen difference to as low as 2 ml/100 ml blood. Reactive hyperemia was accompanied by brain swelling and an increase in intracranial pressure from 3.6 +/- 1.2 to 12.3 +/- 2.0 mm Hg. The reason for hyperemia was a decrease of cortical pH which fell from 7.33 +/- 0.03 to 7.03 +/- 0.05, and which caused a dilation of pial arteries up to 260%. Immediately after embolism, the EEG flattened and oxygen consumption decreased. After normalization of flow, oxygen consumption returned to normal, but EEG only partially recovered. Air embolism had little effect on the water and electrolyte content of the brain, and produced very little damage to the blood-brain barrier.
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PMID:Arterial air embolism in the cat brain. 4 47

The degree of recovery of the somatosensory cortical evoked response following a period (15 to 65 minutes) of partial ischemia, produced by temporary occlusion of the middle cerebral artery (MCA), was assessed in baboons and related to the local tissue blood flow and PO2 before, during and after the occlusion. Flow was measured using the technique of two-minute hydrogen clearance. Failure of complete recovery of the evoked response was associated with significantly greater depths of ischemia and tissue hypoxia during occlusion, and with significantly greater and persisting tissue hypoxia after occlusion, than complete recovery. Complete recovery of the evoked response also was associated with tissue hyperoxia after occlusion. The reduced postocclusive PO2 levels associated with incomplete recovery of the evoked response suggest that reduced perfusion during ischemia was sufficiently severe to cause some degree of irreversible anoxic damage. The effect of a brief (three to ten minutes) period of ventilation with air (instead of oxygen) under such low-flow conditions was to depress the evoked response significantly further; normally perfused brain, however, was unaffected by this procedure. This finding has clinical implications in regard to normobaric oxygen therapy.
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PMID:Recovery of the cortical evoked response following temporary middle cerebral artery occlusion in baboons: relation to local blood flow and PO2. 126 8

Ischemia-reperfusion and hyperoxia-induced pulmonary injury are associated with the presence of activated neutrophils (PMN) and cellular injury. Although the signals orchestrating the directed migration of these PMN during the pathogenesis of these disease states remain to be fully elucidated, it appears they may be dependent upon the production of certain neutrophil activating/chemotactic factors such as C5a, leukotriene B4, platelet-activating factor, and IL-8. The production of the latter chemotaxin by mononuclear phagocytes is especially intriguing as these cells can mediate inflammatory cell migration by either directly generating IL-8, or by inducing its production from surrounding nonimmune cells. In light of these observations, we propose that ischemia-reperfusion and oxidant stress, in vivo, may be simulated by anoxia-hyperoxia induced stress in vitro, and that this stress may act as a stimulus for the production of IL-8. We now show that isolated human blood monocytes respond to such an oxygen stress with augmented production of IL-8. In initial studies, monocytes demonstrated an increase in the production of IL-8 under anoxic preconditioning. Subsequently, monocytes were cultured under one of the following conditions for 24 h: (a) room air/5% CO2; (b) 95% N2/5% CO2 for 6 h, followed by room air/5% CO2 for 18 h; (c) 95% N2/5% CO2 for 6 h, followed by 95% O2/5% CO2 for 18 h; (d) room air/5% CO2 for 6 h, followed by 95% O2/5% CO2 for 18 h; or (e) 95% O2/5% CO2. Supernatants were isolated and analyzed for IL-8 antigen by specific IL-8 ELISA, demonstrating the production of monocyte-derived IL-8: 5.9 +/- 0.9, 11.4 +/- 1.7, 21.1 +/- 2.3, 14.6 +/- 2.4, and 26.3 +/- 4.7, ng/ml by designated conditions a, b, c, d, and e listed above, respectively. This variance in IL-8 production reflects altered rates of transcription as shown by Northern blot analysis and nuclear run-off assay. Furthermore, when monocytes were concomitantly treated with LPS (100 ng/ml) under in vitro hyperoxic conditions, both IL-8 steady-state mRNA and antigenic activity were two- to threefold greater than under room air conditions. The association of anoxic preconditioning and oxygen stress with augmented production of monocyte-derived IL-8 support the potential role for ischemia-reperfusion and hyperoxia-induced IL-8 production in vivo, providing a possible mechanism for PMN migration/activation in disease states characterized by altered tissue oxygenation.
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PMID:Anoxia-hyperoxia induces monocyte-derived interleukin-8. 152 34

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

Oxygen derived free radicals (OFR) arise in the course of normal cellular life, especially during cellular respiration. They are formed when molecular oxygen is reduced to water. These highly reactive species are controlled by a protective system both enzymatic and non enzymatic which helps to prevent the accumulation of peroxidative damage to the cell. Lipid peroxides result from the reaction of oxygen derived free radicals with polyinsatured fatty acids of membranes phospholipids and can be formed both non enzymatically and enzymatically (eicosanoids). Oxygen derived free radicals attack over-running beyond the protective system leads to oxidative stress. The cells involved in inflammation (polymorphonuclear, leucocytes, monocytes, platelets, endothelial cells) release oxygen derived free radicals and lipid peroxides and inflammatory diseases of infectious or non infectious origin can be considered as oxidative stress. Intracellular oxidative stress can lead to cellular death or trigger a strong inflammatory reaction. This occurs during ischemia reperfusion injury and hyperoxia. Exposure to ionizing radiation results in overproduction of oxygen derived free radicals both extra and intracellular. Oxidative stress may be involved in atheroma (where oxidised LDL are described), ageing and cancer.
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PMID:[Free radicals and lipid peroxidation in cell biology: physiopathologic prospects]. 206 58

Reactive oxygen species are a major cause of damage occurring in ischemic tissue after reperfusion. During reperfusion transitional metals such as iron are required for reactive oxygen species to mediate their major toxic effects. Xanthine oxidase is an important source of reactive oxygen species during ischemia-reperfusion injury, but not in all organs or species. Because cytochrome P-450 enzymes are an important pulmonary source of superoxide anion (O2-.) generation under basal conditions and during hyperoxia, and provide iron catalysts necessary for hydroxyl radical (.OH) formation and propagation of lipid peroxidation, we postulated that cytochrome P-450 might have a potential role in mediating ischemia-reperfusion injury. In this report, we explored the role of cytochrome P-450 enzymes in a rabbit model of reperfusion lung injury. The P-450 inhibitors 8-methoxypsoralen, piperonyl butoxide, and cimetidine markedly decreased lung edema from transvascular fluid flux. Cimetidine prevented the reperfusion-related increase in lung microvascular permeability, as measured by movement of 125I-albumin from the vascular space into lung water and alveolar fluid. P-450 inhibitors also prevented the increase in lung tissue levels of thiobarbituric acid reactive products in the model. P-450 inhibitors did not block enhanced O2-. generation by ischemic reperfused lungs, measured by in vivo reduction of succinylated ferricytochrome c in lung perfusate, but did prevent the increase in non-protein-bound low molecular weight chelates of iron after reperfusion. Thus, cytochrome P-450 enzymes are not likely a major source of enhanced O2-. generation, but serve as an important source of iron in mediating oxidant injury to the rabbit lung during reperfusion. These results suggest an important role of cytochrome P-450 in reperfusion injury to the lung and suggest potential new therapies for the disorder.
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PMID:Role of cytochrome P-450 in reperfusion injury of the rabbit lung. 217 18

Carotid arteries were occluded bilaterally for 15 min in two groups of Mongolian gerbils. The first group received 100% oxygen during the first 3 h of reperfusion. During that period, room air was given to the second group. After 3 h, both groups received room air. Brains of gerbils that died within 14 days after occlusion were removed, fixed in formalin and embedded in paraffin. Gerbils that survived 15-28 days were perfused with formalin before their brains were removed and embedded in paraffin. Adjacent, serially cut sections were stained with luxol fast blue (LFB)-H&E, cresyl violet, according to the Bodian method, or immunocytochemically with antisera raised against myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP). In brain sections of gerbils receiving 3 h of 100% oxygen, there were circumscribed white matter lesions in the corpus striatum, lateral thalamus, mesencephalon and posterior limb of the internal capsule. Myelin sheaths were swollen, fragmented and were less intensely stained by MBP antiserum. MBP and LFB-stained myelin fragments were present extracellularly and in macrophages. Many axons in these areas appeared undamaged. Previously described ischemic changes were found in gray matter and some areas of white matter in both groups. However, neurons in the deeper laminae of the cerebral cortex appeared to be better preserved in gerbils given oxygen. The results suggest that hyperoxia, if present immediately after transient brain ischemia, may damage myelin more severely than other cellular elements.
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PMID:Prominent white matter lesions develop in Mongolian gerbils treated with 100% normobaric oxygen after global brain ischemia. 232 46

Transretinal PO2 profiles were recorded with O2-sensitive microelectrodes in the normal retina and in ischemic retinal foci induced by the occlusion of a retinal branch vein with argon laser photocoagulation in anesthetized miniature pigs. In the normal retina there are two PO2 gradients: one from the inner retina and the other from the choroid, both directed toward the middle of the retina. Both PO2 gradients persisted during hyperoxia. Thus, even in hyperoxia, the choroid does not supply the whole thickness of the normal retina with O2. Preretinal and transretinal PO2 measurements in ischemic inner retinal foci showed the existence of two PO2 gradients in steady-state systemic normoxia, as did those in the normal retina. This finding indicates that even in ischemia the choroid does not supply O2 to the inner retina; as a result, tissue hypoxia is maintained. During systemic hyperoxia, the intraretinal PO2 measurements in the ischemic foci showed only one gradient going from the choroid toward the inner retina. This gradient indicates that under these conditions, the choroid can supply O2 to the entire thickness of the ischemic retina. Extending a previously formulated hypothesis, we propose that in the ischemic retina as opposed to the normal retina, hyperoxia does not induce an increase in the O2 consumption of the outer retina. This suggestion could explain the rise in PO2 in the inner ischemic retina during hyperoxia.
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PMID:Diffusion of O2 in normal and ischemic retinas of anesthetized miniature pigs in normoxia and hyperoxia. 233 51

Imposition of ischemia should result in accumulation of lactic acid with an attendant drop in pH. Subsequent reperfusion would result in hyperoxia, in the affected tissue, due to the Bohr Effect. O2- should therefore be produced in greater than normal amounts, due to this transient hyperoxia, and may contribute to reperfusion injury. Tissue acidification, during extreme exercise or in diabetes mellitus, may similarly lead to hyperoxia and to tissue damage by O2-.
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PMID:Hyperoxia during reperfusion is a factor in reperfusion injury. 234 Oct 57

Cell injury from hyperoxia is associated with increased formation of superoxide radicals (O2-). One potential source for O2- radicals is the reduction of molecular O2 catalyzed by xanthine oxidase (XO). Physiologically, this reaction occurs at a relatively low rate, because the native form of the enzyme is xanthine dehydrogenase (XD) which produces NADH instead of O2-. Reports of accelerated conversion of XD to XO, and increased formation of O2- formation in ischemia-reperfusion injury, led us to examine whether hyperoxia, which is known to increase O2- radical formation, is associated with increased lung XO activity, and accelerated conversion of XD to XO. We exposed 3-month-old rats either to greater than 98% O2 or room air. After 48 h, we sacrificed the rats and measured XD and XO activities and uric acid contents of the lungs. We also measured the activities of the two enzymes in the heart as a control organ. We found that the activity of XD was not altered significantly by hyperoxia in rat lungs or hearts, but XO activity was markedly lower in the lung, whether expressed per whole organ or per milligram protein, and remained unchanged in the heart. Lung uric acid content was also significantly lower with hyperoxia. The decrease in lung XO activity may reflect inactivation of the enzyme by reactive O2 metabolites, possibly as a negative feedback mechanism. The concomitant decrease in uric acid content suggests either decreased production mediated by XO due to its inactivation or greater utilization of uric acid as an antioxidant. We examined these postulates in vitro using a xanthine/xanthine oxidase system and found that H2O2, but not uric acid, has an inhibitory effect on O2- formation in the system. We therefore conclude that hyperoxia is not associated with increased conversion of XD to XO, and that the exact contribution of XO to hyperoxic lung injury in vivo remains unclear.
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PMID:Hyperoxia and xanthine dehydrogenase/oxidase activities in rat lung and heart. 254 69


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