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

Ischemia-reperfusion injury has been associated with intracellular H2O2 and superoxide radical production from accumulated hypoxanthine (HX) and xanthine oxidase (XO). The effect of H2O2 and superoxide radical on mitochondrial Ca2+ efflux was characterized in isolated renal mitochondria using a HX-XO system. Mitochondria were suspended in buffered medium containing 200 microM HX. Extramitochondrial Ca2+ was monitored kinetically at 660-685 nm using the Ca2+ indicator arsenazo III. After preloading mitochondria with 18-25 nmol Ca2+/mg protein, addition of XO to the medium caused a rapid oxidation of mitochondrial NAD(P)H followed by Ca2+ release. Ca2+ efflux was attributed to mitochondrial metabolism of H2O2 because efflux could be prevented with catalase but not superoxide dismutase. The Ca2+ efflux rate (r = 0.995) and lag time to Ca2+ efflux (r = 0.987) both correlate well with the NAD(P)H oxidation rate. Exogenous ATP prevents Ca2+ efflux in a dose-dependent fashion (Km = 35 microM ATP) without affecting NAD(P)H oxidation; ATP plus oligomycin, however, had no effect. The protective effect of ATP on Ca2+ efflux was diminished by ruthenium red (RR). XO-induced Ca2+ efflux increased state 4 respiration 148% via a futile Ca2+ cycle involving the Ca2+ uniport. The increase in state 4 respiration could be reversed with RR (alpha less than 0.001) or ATP (alpha less than 0.01); ATP plus oligomycin, however, had no effect. The results are discussed in relation to the oxygen free radical theory of reperfusion injury.
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PMID:Potential role of mitochondrial calcium metabolism during reperfusion injury. 273 95

Perfusion of rat hearts with Krebs-Henseleit bicarbonate buffer containing low concentrations of hydrogen peroxide or t-butylhydroperoxide (50-500 microM) caused an imbalance in the relative synthesis versus utilization rates of ATP, leading to a net hydrolysis of ATP and phosphocreatine. Hydrogen peroxide also caused an 80% inactivation of glyceraldehyde-3-phosphate dehydrogenase, resulting in an inhibition of glycolysis and a rapid accumulation of sugar phosphates as detected with 31P-NMR spectroscopy. This inhibition was partially reversible with peroxide-free perfusion, resulting in a cessation of high-energy-phosphate hydrolysis and a decrease in the accumulated inorganic phosphate and sugar phosphate. t-Butylhydroperoxide toxicity was irreversible. Providing an alternative, non-glycolytic substrate (butyrate) did not protect against the toxicity of hydrogen peroxide, but altered the relative importance of sugar phosphate formation versus ATP hydrolysis. Experiments with heart homogenates in vitro suggest that the inhibition of glyceraldehyde-3-phosphate dehydrogenase is a consequence of a direct reaction of the enzyme with hydrogen peroxide or one of its metabolites. Hearts subjected to total global ischemia (10-20 min), followed by reperfusion with oxygenated buffer, showed no detectable inactivation of glyceraldehyde-3-phosphate dehydrogenase, indicating that ischemia and reperfusion do not result in the production of high global concentrations of hydrogen peroxide.
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PMID:The metabolic consequences of hydroperoxide perfusion on the isolated rat heart. 280 48

Perfusion with human serum albumin decreased myocardial hydrogen peroxide (H2O2) levels (as assessed by inactivation of myocardial catalase activities following aminotriazole pretreatment) and increased myocardial ventricular developed pressures (DP), contractility (+dP/dt) but not relaxation rate (-dP/dt) in isolated crystalloid perfused rat hearts subjected to normothermic global ischemia (20 min) and then reperfusion (40 min). Albumin also decreased H2O2 concentrations in vitro. The findings support the possibility that albumin may act as a protective O2 metabolite scavenger in vivo.
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PMID:Albumin decreases hydrogen peroxide and reperfusion injury in isolated rat hearts. 280 21

The release of oxygen free radicals from ischemic myocardial tissue has been implicated as a causative factor of cell membrane damage and cardiac dysfunction in hemorrhagic shock. This study was done to determine whether or not hydrogen peroxide (H2O2) and superoxide ion (O2) are responsible for cardiac injury from hemorrhagic shock as indicated by reduced coronary perfusion and impaired contractile function. This hypothesis was tested by infusing selective O2 and H2O2 scavengers into anesthetized dogs in a state of shock, either during shock (group 3) or with fluid resuscitation (group 2) and comparing the cardiovascular response to that seen with shock and fluid resuscitation alone (group 1). We found no significant difference in shock induced derangements in myocardial oxygen metabolism or the degree of myocardial depression and regional ischemia in dogs in a state of shock given superoxide dismutase plus catalase, compared with shock alone. The results of our data suggested that, if O2 and H2O2 play a causative role in shock induced cardiac dysfunction or during reperfusion after shock, free radical scavengers must be administered early in the ischemic period. Furthermore, free radical scavengers administered with reperfusion do not enchance cardiac function nor myocardial perfusion.
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PMID:Possible role of oxygen-derived, free radicals in cardiocirculatory shock. 282 38

Oxidant species such as superoxide radical (O.2-), hydrogen peroxide (H2O2), hydroxyl radical (HO.), and lipid peroxides (LOOH) are becoming increasingly implicated in human disease. However, the question of whether such oxidants are a major cause of tissue injury in human disease or are merely produced during such injury has been difficult to answer because of inadequate experimental techniques, and possibly because of an overemphasis on lipid peroxidation as a mechanism of oxidant injury. Recent developments in methodology, in our understanding of the primary mechanism of oxidant toxicity to cells, and in concepts of antioxidant protection are reviewed. Good evidence now exists for some role of oxidant damage to tissues in the pathology of several human diseases, including rheumatoid arthritis, reperfusion injury, immune injury to lung and kidney, and cerebral trauma or ischemia. These have led to promising suggestions for new therapeutic approaches.
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PMID:Oxidants and human disease: some new concepts. 282 68

The results of our experiments demonstrated that one hour of ischemia followed by one hour of reflow in the kidney caused a reduction in (Na+K+)ATPase activity and microsomal sulfhydryl content as well as an increase in microsomal lipid peroxidation. Renal venous malondialdehyde concentration was increased soon after reperfusion of the ischemic kidney. All these changes were rectified by an infusion of 0.123 mmol N-(2-mercaptopropionyl)glycine/kg over a 70 min period. On the other hand, an in vitro addition of 0.01-0.5 mM N-(2-mercaptopropionyl)glycine to a membrane preparation in the presence of H2O2 and Fe3+ did not prevent but rather potentiated the free radical effect on the enzyme activity. However, addition of superoxide dismutase alone or with catalase together with 2-MPG were effective in preventing the enzyme depression induced by H2O2. The results therefore indicate that free radical generation participates in the evolution of ischemia/reperfusion cell injury and thiol-reducing agents may be beneficial in alleviating the cell damage in vivo.
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PMID:Effects of N-(2-mercaptopropionyl)glycine on ischemic-reperfused dog kidney in vivo and membrane preparation in vitro. 283 50

A partially purified, membrane-bound Na+-K+-ATPase fraction, prepared from the outer medulla of porcine kidney, was incubated in the presence of 0.1 mM FeCl3, 1 mM ADP, and 0.1-100 mM H2O2 for either 15 or 30 min at 37 degrees C. The activity of ouabain-sensitive Na+-K+-ATPase was reduced proportionally to the concentration of H2O2 and the duration of incubation. There were decreases in SH contents and turnover rates of the Na+-K+-ATPase preparation, while malondialdehyde (MDA) and conjugated dienes were generated from the membrane lipids in the course of the incubation. The concentrations of ethanolamine (E) plasmalogen and of arachidonic acid in the E glycerophospholipid molecules were reduced by the free radical reaction. Similarly, a reduction in Na+-K+-ATPase activity and the formation of MDA and conjugated dienes, together with a decrease in E glycerophospholipids, were observed when the membrane fraction was exposed to ultraviolet irradiation (254 nm) for 30 min at 4 degrees C. Administration of 10 mM dithiothreitol alleviated the reductions in enzyme activity, in turnover rate, and in SH content without suppressing MDA formation. Addition of 2 mM butylated hydroxytoluene to the incubation mixture prevented the lipid peroxidation without totally normalizing the enzyme activity in the H2O2 experiment, whereas this antioxidant restored the ATPase activity to normal in the ultraviolet experiment. Microsomal fractions, prepared from the outer medulla of canine kidney after 1 h of unilateral ischemia and 1 h of reperfusion, showed a decreased Na+-K+-ATPase activity, a reduced amount of SH groups, and an increased MDA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Depression of membrane-bound Na+-K+-ATPase activity induced by free radicals and by ischemia of kidney. 283 28

The hypothesis that mitochondria damaged during complete cerebral ischemia generate increased amounts of superoxide anion radical and hydrogen peroxide (H2O2) upon postischemic reoxygenation has been tested. In rat brain mitochondria, succinate supported H2O2 generation, whereas NADH-linked substrates, malate plus glutamate, did so only in the presence of respiratory chain inhibitors. Succinate-supported H2O2 generation was diminished by rotenone and the uncoupler carbonyl cyanide m-chlorphenylhydrazone and enhanced by antimycin A and increased oxygen tensions. When maximally reduced, the NADH dehydrogenase and the ubiquinone-cytochrome b regions of the electron transport chain are sources of H2O2. These studies suggest that a significant portion of H2O2 generation in brain mitochondria proceeds via the transfer of reducing equivalents from ubiquinone to the NADH dehydrogenase portion of the electron transport chain. Succinate-supported H2O2 generation by mitochondria isolated from rat brain exposed to 15 min of postdecapitative ischemia was 90% lower than that of control preparations. The effect of varying oxygen tensions on H2O2 generation by postischemic mitochondrial preparations was negligible compared with the increased H2O2 generation measured in control preparations. Comparison of the effects of respiratory chain inhibitors and oxygen tension on succinate-supported H2O2 generation suggests that the ability for reversed electron transfer is impaired during ischemia. These data do not support the hypothesis that mitochondrial free radical generation increases during postischemic reoxygenation.
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PMID:Generation of hydrogen peroxide by brain mitochondria: the effect of reoxygenation following postdecapitative ischemia. 291 86

To investigate the specific nature and timing of oxygen (O2) metabolite reperfusion injury, we used a rat-heart model (Langendorff's solution, 37 degrees C) and hydrogen peroxide (H2O2)-dependent aminotriazole inactivation of catalase as a measure of myocardial H2O2 before, during, and after ischemia. We found that after ischemia (20 minutes, global, 37 degrees C), ventricular functional loss--as assessed by measurement of developed pressure (DP), +dp/dt, and -dp/dt with a ventricular balloon--occurred at 10 minutes of reperfusion and that myocardial H2O2 production was maximal by this time. Furthermore, H2O2 production did not occur during ischemia, and inhibition of xanthine oxidase by tungsten feeding or infusing a permeable O2 metabolite scavenger during reperfusion (dimethylthiourea) prevented ventricular functional loss. We conclude that (1) reperfusion injury is in part mediated by toxic oxygen metabolites, (2) H2O2 is the central O2 metabolite responsible for reperfusion injury, and (3) the timing of H2O2 production coincides with the timing of ventricular functional loss.
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PMID:The coincidence of myocardial reperfusion injury and hydrogen peroxide production in the isolated rat heart. 292 52

The pathways for the metabolism of molecular oxygen involve one electron-transfer reaction with the subsequent production of reduced-oxygen intermediates. These reduced-oxygen intermediates include the superoxide anion (.O2-), hydrogen peroxide (H2O2), and the hydroxyl radical (.OH), which are highly reactive, short-lived species. Normally intracellular enzyme systems that include superoxide dismutase, catalase, and glutathione peroxidase are responsible for "scavenging" these products of oxygen metabolism. However, in many pathological states such as inflammation, ischemia, and reperfusion, there is an increased production of these reduced-oxygen intermediates, which are capable of extensive tissue damage. It is the purpose of this symposium to examine, in depth, the role of oxygen free radical systems as mediators of myocardial dysfunction and expand our knowledge of myocardial ischemia, ischemia-reperfusion injury, and the inflammatory response of the myocardium.
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PMID:The oxygen free radical system and myocardial dysfunction. 298 5


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