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

Xanthine oxidase activity in the rat brain was measured by means of high-performance liquid chromatography with electrochemical detection of uric acid. Cerebral ischemia was produced by a four-vessel occlusion method. In the control rat, the enzyme activity was 0.87 +/- 0.13 nmol/gm wet weight/min at 25 degrees C (mean +/- standard deviation), of which 92.4% was associated with the nicotinamide adenine dinucleotide (NAD)-dependent dehydrogenase form and only 7.6% with the oxygen-dependent superoxide-producing oxidase form. However, the ratio of the latter form increased to 43.7% after 30 minutes of global ischemia, despite the total xanthine oxidase activity remaining the same. Thus, it was revealed that uric acid can be synthesized in the rat brain and that cerebral ischemia induced the conversion of xanthine oxidase from an NAD-dependent dehydrogenase to an oxygen-dependent superoxide-producing oxidase. Although the xanthine oxidase pathway has been proposed as a source of oxygen-derived free radicals in various ischemic organs other than brain, the results of the present study suggest the involvement of the oxygen free radicals generated from this pathway in the pathogenesis of the ischemic injury of the rat brain.
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PMID:Changes in xanthine oxidase in ischemic rat brain. 254 24

To clarify the mechanism of its effect on ischemic stroke, we investigated the effect of nimodipine, a dihydropyridine calcium antagonist, on changes in cytosolic free calcium, cortical blood flow, and histologic changes following focal cerebral ischemia and reperfusion in 14 cats. Using indo-1, a fluorescent intracellular Ca2+ indicator, we simultaneously measured changes in the Ca2+ signal ratio (400:506 nm), reduced nicotinamide adenine dinucleotide fluorescence (464 nm), and reflectance (340 nm) during an ultraviolet excitation (340 nm) directly from the cat cortex in vivo. In six cats treated with vehicle only, the calcium signal ratio increased from 5 minutes after middle cerebral artery occlusion to 30 minutes into reperfusion. The elevation of cytosolic free calcium was significantly attenuated by nimodipine, which was administered by intravenous infusion in eight cats starting 5 minutes after occlusion. Nimodipine had no effect on cortical blood flow during ischemia but induced a hyperperfused state following reperfusion. Nimodipine did not modify changes in the mitochondrial oxidation-reduction state. Nimodipine proved to have beneficial effects on recovery of the electroencephalogram following reperfusion as well as on the extent of focal histologic damage. Our results suggest that nimodipine, when administered during the early stage of focal ischemia, can favorably modify the outcome of stroke by reducing the Ca2+ entry during both the ischemic and reperfusion periods.
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PMID:Nimodipine attenuates both increase in cytosolic free calcium and histologic damage following focal cerebral ischemia and reperfusion in cats. 281 88

Excitatory amino acids have been implicated in ischemic neuronal injury. To test this hypothesis in neonatal hypoxia-ischemia, lesions of the cortex and striatum were induced in 7-day-old rats by unilaterally ligating their carotid arteries and subjecting them to hypoxic conditions for 2 hours. Brains examined 1 week later demonstrated, within the regions of ischemic damage, a striking preservation of neurons that stained histochemically for nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) activity. Concentrations of the neuropeptides somatostatin and neuropeptide Y, which colocalize in neurons containing NADPH-d, were unaffected in the areas of ischemic damage. The same pattern of injury with sparing of NADPH-d-reactive neurons was reproduced by focal microinfusion of the excitotoxin quinolinic acid, an endogenous N-methyl-d-aspartate (NMDA) agonist, into the striatum. These results support the hypothesis that neonatal hypoxic-ischemic injury is mediated through excitatory transmitters acting at the NMDA receptor and that the NADPH-d-reactive neurons in the neonate are resistant to excitotoxic damage. This pattern of cell vulnerability is unique to the developing striatum and may relate to the distinct pathological appearance of the basal ganglia that follows neonatal asphyxia.
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PMID:Selective sparing of NADPH-diaphorase neurons in neonatal hypoxia-ischemia. 290 92

An increase in cytosolic free calcium concentration ([Ca2+]i) may trigger irreversible cell injury following cerebral ischemia. We have measured changes in [Ca2+]i in cat cortex in vivo during ischemia produced by 1 hour of middle cerebral artery occlusion and during 30 minutes of reperfusion. Indo-1, a fluorescent Ca2+ indicator, was loaded into the exposed cortex by superfusion, and changes in the [Ca2+]i signal (400/506 nm ratio) were measured microfluorometrically during ultraviolet excitation (340 nm). The nicotinamide adenine dinucleotide/reduced nicotinamide adenine dinucleotide (NAD/NADH) redox state and hemodynamic changes were measured simultaneously. The animals showing severe deterioration in their electroencephalograms (EEG) showed a progressive increase in the [Ca2+]i signal during ischemia (baseline: 1.46 +/- 0.05; 60 minutes after occlusion: 2.99 +/- 0.37; n = 7). At 30 minutes following reperfusion, the animals showing little recovery in their EEG exhibited a further increase in [Ca2+]i (4.71 +/- 0.87, n = 3), whereas animals showing significant recovery in their EEG also showed recovery of [Ca2+]i (1.55 +/- 0.09, n = 4). By contrast, the moderate or mild stroke animals with less deterioration in their EEGs showed no increase in [Ca2+]i during either ischemia or reperfusion. These data suggest that the increase in [Ca2+]i might be closely related not only to deterioration of brain function during ischemia but also to poor recovery during the reperfusion period.
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PMID:In vivo measurement of cytosolic free calcium during cerebral ischemia and reperfusion. 314 14

We examined the possibility that in preeclampsia complicated by fetal growth retardation, placental energy state is low either because of impaired glycolysis or because of ischemia resulting from reduced maternal placental blood flow. Concentrations of pyruvate and lactate, but not of glycogen and glucose, were significantly low in placentas of mothers with severe preeclampsia, supporting previous indirect evidence of inhibited glycolysis. Nevertheless, direct measurements of adenine nucleotide concentrations did not indicate reduced placental energy level in the preeclamptic placentas. This along with a lack of change of the ratio of lactate/pyruvate concentration (an indication of the redox state of cytoplasmic reduced nicotinamide adenine dinucleotide/nicotinamide adenine dinucleotide) is also evidence against the hypothesis of general placental ischemia leading to energy deficiency. However, as glycolysis is an important source of precursors, particularly pyruvate, for synthesis of amino acids and lipids, these results suggest that there is a significant metabolic abnormality in placentas of mothers with severe preeclampsia.
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PMID:Placental glycolysis and energy metabolism in preeclampsia. 360 74

Recent evidence suggests that oxygen free radicals are largely responsible for the increased vascular permeability and early mucosal lesions associated with partial intestinal ischemia. It is postulated that oxygen radicals are produced by the reaction of the enzyme xanthine oxidase with hypoxanthine and molecular oxygen. In normal healthy cells, xanthine oxidase exists as a nicotinamide adenine dinucleotide-reducing dehydrogenase and not the oxygen radical-producing oxidase. In the intestine, dehydrogenase-to-oxidase conversion is nearly complete with less than 1 min of ischemia. Biochemical evidence from the intestine and liver indicate that ischemia-induced conversion of xanthine dehydrogenase to xanthine oxidase can be prevented by administration of protease inhibitors such as soybean trypsin inhibitor. In order to assess the role of proteases in oxygen radical-mediated ischemic injury to the small bowel, quantitative analyses of mucosal lesion development and vascular permeability were performed in autoperfused segments of cat ileum subjected to 1 or 3 h of ischemia and pretreated with 15 mg/kg (i.v.) soybean trypsin inhibitor. One hour of ischemia produced a significant increase in intestinal vascular permeability. The ischemia-induced increase in vascular permeability was significantly attenuated by soybean trypsin inhibitor pretreatment. Three hours of ischemia led to the development of mucosal lesions in untreated animals. Pretreatment with soybean trypsin inhibitor largely prevented the development of the mucosal lesions. The findings of our study are consistent with biochemical evidence that, during ischemia, proteases trigger the conversion of xanthine dehydrogenase to xanthine oxidase and thereby lead to oxygen radical production and subsequent tissue injury.
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PMID:Soybean trypsin inhibitor attenuates ischemic injury to the feline small intestine. 400 13

Experiments on mice with simulated isobaric hypoxia and anoxia have demonstrated marked antihypoxic action of a complex of vitamins with electron-acceptor activity (ascorbic acid, riboflavine mononucleotide, lipoic acid, nicotinamide). In dog experiments, the complex of vitamins reduced metabolic acidosis in the ischemia zone as shown by the lactate release test and increased the collateral coronary circulation. The protective action of the drug recorded in hypoxia and regional myocardial ischemia is regarded as linked with the ability of the vitamin complex to raise the conjugation of oxidation and phosphorylation in the mitochondria of a pathologically altered myocardium, as well as with its membrane-stabilizing action and inhibition of lipid peroxidation.
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PMID:[Action of a vitamin complex with oxidative-reductive properties on the course of acute myocardial hypoxia and ischemia]. 624 Apr 10

Various metabolic, cellular, and subcellular alterations in cell function and morphology occur during shock or low-flow conditions. In attempting to find treatment programs that would be beneficial following shock, various substrates have been used. Infusion of hypertonic glucose during shock has been shown to improve survival; however, it is unlikely that the effect of glucose is by provision of energy until the circulation is restored. Infusion of glucose--insulin--potassium during shock has also been reported to be beneficial in certain clinical situations. Controversies exist concerning the efficacy of infusions of cyclic AMP, nicotinamide, and Krebs cycle intermediates during shock. Pretreatment of kidneys with inosine or raising glycogen stores of the myocardium have been shown to have protective effects of kidneys and myocardium during ischemia and these procedures may be suitable for organ preservation. Pretreatment with allopurinol has been shown to be beneficial in shock; however, it is unlikely that allopurinol by itself if given following shock would have any salutary effects. Treatment with ATP-MgCl2 has been shown to be beneficial following hemorrhagic shock, sepsis, endotoxin shock, burns, postischemic hepatic failure, and postischemic renal failure. Thus, provision of energy directly in the form of ATP during adverse circulatory conditions appears to be the most advantageous and direct method for the treatment of shock.
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PMID:The use of substrates and energy in the treatment of shock. 627 59

We investigated if the loss of nicotinamide coenzymes in ischemic-infarcted myocardium may be responsible for the transition from reversibly ischemic to irreversibly infarcted cell damage. The LAD was occluded in 6 dogs for 4 h. Transmural needle biopsies were taken from he ischemic-infarcted region after 1/2, 1, 11/2, 2, and 4 h of ischemia and further divided into subepicardial and subendocardial halves. At each time interval the concentration of the nicotinamide coenzymes NAD, NADH, and NADPH were measured, and the degree of cellular injury was evaluated by electron microscopy. The glycohydrolase activity (EC 3.2.2.5), the enzyme which splits NAD, was determined in brain, myocardium, kidney, and skeletal muscle of 4 rats. Total NAD, the sum of NAD and NADH, started to decrease significantly in the ischemic subendocardium 1 h after onset of ischemia. Degradation of NADPH occurred later. Loss ot total NAD was about 60-70% when electron microscopy diagnosed irreversible cell injury. The glycohydrolase activity was the highest in brain followed by myocardium, kidney, and skeletal muscle, reflecting the different tolerances of these tissues towards ischemia. The key mechanism for ischemic injury seems to be the tissue acidosis which activates the glycohydrolase leading to a loss of the vital coenzymes.
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PMID:Loss of canine myocardial nicotinamide adenine dinucleotides determines the transition from reversible to irreversible ischemic damage of myocardial cells. 627 93

Direct recording of reduced nicotinamide adenine dinucleotide (NADH) fluorescence was conducted with an organ redoximeter in isolated perfused guinea pig heart. Cross-clamping of the aortic inflow line resulted in an increase in NADH fluorescence. After etafenone (10(-6) M), there was a significant prolongation of the time to the detectable or the maximum increase in NADH fluorescence. The magnitude of the increase in NADH fluorescence tended to be reduced (135% as compared with 145% in the control group). Supplemental chemical analyses revealed a significant increase in creatine phosphate, adenosine triphosphate (ATP) and total adenine nucleotide in the etafenone-pretreated group 15 min after postischemic reperfusion, although the ischemia-induced changes were not improved by this compound. It was suggested that the better recovery of myocardial high energy phosphate levels produced by etafenone was brought about by a decrease in oxygen consumption due to a decrease in mechanical performance of the heart and possibly by a better resynthesis of ATP.
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PMID:Effects of etafenone on myocardial energy metabolism as studied by an organ redoximeter and biochemical analyses. 648 88


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