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

The effects of a potent adenosine deaminase inhibitor, deoxycoformycin, on purine and amino acid neuro-transmitter release from the ischemic rat cerebral cortex were studied with the cortical cup technique. Cerebral ischemia (20 min) was elicited by four-vessel occlusion. Purine and amino acid releases were compared from control ischemic animals and deoxycoformycin-pretreated ischemic rats. Ischemia enhanced the release of glutamate, aspartate, and gamma-aminobutyric acid into cortical perfusates. The levels of adenosine, inosine, hypoxanthine, and xanthine in the same perfusates were also elevated during and following ischemia. Deoxycoformycin (500 micrograms/kg) enhanced ischemia-evoked release of adenosine, indicating a marked rise in the adenosine content of the interstitial fluid of the cerebral cortex. Inosine, hypoxanthine, and xanthine levels were depressed by deoxycoformycin. Deoxycoformycin pretreatment failed to alter the pattern of amino acid neurotransmitter release from the cerebral cortex in comparison with that observed in control ischemic animals. The failure of deoxycoformycin to attenuate amino acid neurotransmitter release, even though it markedly enhanced adenosine levels in the extracellular space, implies that the amino acid release during ischemia occurs via an adenosine-insensitive mechanism. Inhibition of excitotoxic amino acid release is unlikely to be responsible for the cerebroprotective actions of deoxycoformycin in the ischemic brain.
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PMID:Brain adenosine and transmitter amino acid release from the ischemic rat cerebral cortex: effects of the adenosine deaminase inhibitor deoxycoformycin. 167 Oct 90

This study was designed to clarify the mechanism of ischemia-reperfusion-induced rat liver injury and to evaluate the effect of long-acting superoxide dismutase (SOD-POE). Liver mitochondrial functional indices, i.e., the respiratory control index (RCI) and the rate of oxygen consumption in State III respiration (St. III O2), were decreased significantly to 1.33 +/- 0.06, mean +/- SD, and 54.4 +/- 3.7 natom/mg protein/min, respectively, after 120 min of ischemia, compared to respective preischemic values (3.94 +/- 0.21 and 80.2 +/- 3.9). These indices did not recover fully following 60 min of reperfusion (RCI, 3.25 +/- 0.17; St. III O2, 69.9 +/- 6.4). Tissue levels of adenosine triphosphate (ATP) were decreased to 2% of preischemic levels after 120 min of ischemia and remained at 39% of preischemic levels following 60 min of reperfusion. Increases in hypoxanthine and xanthine were observed after ischemia. SOD-POE improved the recovery of mitochondrial function (RCI, 3.70 +/- 0.20; St. III O2, 83.3 +/- 7.6) and also accelerated the recovery of ATP (53% of preischemic level). SOD-POE did not affect the decrease in ATP levels or the increase in purine nucleotide levels during ischemia. SOD-POE did not influence changes in tissue blood flow levels throughout the experiments. The leakage of adenine nucleotides immediately after reperfusion was observed (4.2 +/- 2.0 mumole/liter serum), and SOD-POE mitigated this leakage (1.3 +/- 0.5). Purine nucleotides are oxidizable substrates of xanthine oxidase, and an increase in superoxide radical generation by this enzyme might be expected in the ischemia-reperfusion process.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanism and prevention of ischemia-reperfusion-induced liver injury in rats. 188 Nov 38

The purpose of this study was to better characterize renal adenine nucleotide pool responses to different forms of shock, contrast the changes to those found in other intra-abdominal organs (the liver and small intestine), and assess whether these changes are closely mimicked by those produced by renal arterial occlusion, the usual method used to study ischemic acute renal failure. Rats were subjected to hemorrhagic shock, septic shock, or cardiopulmonary shock of varying severities and durations. The liver consistently had the greatest energy depletion, followed by the kidney, and then the small intestine. However, only the kidney developed clear morphological damage (S3 brush border sloughing). Kidney adenylate pools were better preserved during septic shock and cardiopulmonary shock than during hemorrhagic shock despite comparable blood pressures. Only profound hemorrhagic shock (35-40 mm Hg for 25 minutes) decreased total adenylate pools (ATP + ADP + AMP). However, the degree of renal catabolite (nucleosides plus purine base) accumulation did not correlate with the amount of renal total adenine nucleotide depletion, partially because circulating catabolites contributed to intrarenal catabolite pools. Purine base/uric acid ratios differed among shocked organs, consistent with different degrees of xanthine oxidase activity (small intestine greater than liver greater than kidney). Renal morphological damage decreased during the immediate (0-30 minutes) postshock period, and the extent of this improvement was not altered by xanthine oxidase inhibition (oxypurinol), suggesting that the immediate postshock period is not one of serious oxidative injury. Shock, in comparison with renal arterial occlusion, caused only modest ATP loss/catabolite accumulation, very low purine base/uric acid ratios, and no immediate-reperfusion (0-30 minutes) resynthesis of the total adenylate pool. Thus, ischemia-induced renal adenylate changes may differ considerably, depending on the nature of the ischemic event.
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PMID:Adenine nucleotide changes in kidney, liver, and small intestine during different forms of ischemic injury. 198 61

This study was designed to demonstrate the concentration-dependent effects of an exogenous free-radical-generating system on the functional characteristics of isolated perfused guinea pig hearts under normal conditions and in response to conditions associated with ischemia followed by reperfusion. Purine (0.0115-0.23 mM) and xanthine oxidase (0.05-1.0 U/L) were added to normal Tyrode's solution and perfused for 40 min. Purine (0.0575-0.23 mM)/xanthine oxidase (0.25-1.0 U/L) produced a decline in contractile force that ranged from 59 to 44% of initial values (p less than 0.05). Although all concentrations of the free-radical-generating system enhanced resting tension when compared to control, this increase was only significant in the presence of purine (0.0115 and 0.0575 mM)/xanthine oxidase (0.05 and 0.25 U/L), following a 20-40 min perfusion period (p less than 0.05). Significant correlations were found between the concentration of the free-radical-generating system and the depression in contractile force (p less than 0.05), as well as between the loss of force and the enhancement of resting tension (p less than 0.002) in the presence of all concentrations of purine/xanthine oxidase examined. Furthermore, purine/xanthine oxidase was a potent stimulus for release of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha). While this release was correlated significantly with the concentration of purine/xanthine oxidase (p less than 0.001), there was no significant relationship between the decline in contractile force and the release of 6-keto-PGF1 alpha per se.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Concentration-dependent effects of purine/xanthine oxidase on release of 6-keto-PGF1 alpha and contractile function of isolated guinea pig hearts: response to "ischemic" conditions followed by reperfusion. 247 69

Hypoxia and ischemia are potent stimuli to vascular growth. The mechanisms by which vascular growth is induced are unknown. During ischemia, such as that which occurs in the heart, purine and pyridine nucleotides are degraded and their metabolites accumulate. At least two of these metabolites, adenosine and nicotinamide, have previously been demonstrated to induce vascular growth. The goal of this study was to determine whether other purine and pyridine metabolites have the potential to stimulate angiogenesis in vivo, to determine the relative angiogenic potency of these metabolites, and to determine if their angiogenic effects is mediated through a direct effect on endothelial cell proliferation. Purine metabolites (adenosine, inosine, hypoxanthine, xanthine, guanosine, uric acid), the pyridine metabolite nicotinamide, and chemical derivatives of nicotinamide, were tested at various concentrations for their ability to stimulate angiogenesis in the chick choriollantoic membrane assay. Although none of the purine metabolites were effective in promoting the angiogenic response, nicotinamide as well as several derivatives of nicotinamide induced an angiogenic response in a dose-dependent manner. Nicotinamide was then evaluated to determine if its angiogenic effect is a result of a direct effect on capillary endothelial cell proliferation. In concentrations of 100 microM to 1 mM nicotinamide was not demonstrated to be mitogenic for bovine capillary endothelial cells. These results demonstrate that pyridine nucleotides are indirect angiogenic agents that do not exert a primary effect on endothelial cell proliferation. The results of this study suggest that increases in vascular growth induced by ischemia and hypoxia might be mediated, at least in part, by pyridine metabolites released from ischemic tissues.
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PMID:Angiogenic potency of nucleotide metabolites: potential role in ischemia-induced vascular growth. 252 26

Purine degradation products were determined in the human heart coronary sinus effluent collected from patients undergoing cardiac surgery, during infusion of a cardioplegic solution. At the onset of cardiopulmonary bypass the mean concentrations of adenosine, inosine and hypoxanthine were 0.1, 0.5 and 0.3 mumol/l, respectively. Ischemic arrest leads to a progressive increase of the respective levels to 1.4 17.8 and 9.6 mumol/l after 60-80 min of ischemia. Xanthine concentration was undetectable (less than 0.2 mumol/l) throughout. A substantial urate release (20 mumol/l) was observed which decreased with the duration of ischemia. Xanthine oxidoreductase activity in human myocardium was found to be below the detection limit (0.1 mU/g wet weight). Thus, urate release represented wash out of urate which had accumulated in the tissue.
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PMID:Adenylate degradation products release from the human myocardium during open heart surgery. 275 81

The effect of blocking N-methyl-D-aspartate (NMDA)-sensitive excitatory amino acid (EAA) receptors during brain ischemia was studied in order to test a link between EAAs and neuronal energy metabolism. The receptors were blocked unilaterally in the rat striatum before, during and after an ischemic insult. The receptor blocker, D-2-amino-5-phosphonovalerate (D-APV) was administered by dialysis perfusion, which also allowed continuous sampling for analysis of adenosine triphosphate degradation products, i.e. purine catabolites, in control and D-APV-treated striata. Purine catabolites were analysed with reversed-phase liquid chromatography. Hypoxanthine, xanthine, inosine and adenosine increased dramatically in the striatum during ischemia and reached maximum levels during early reperfusion. D-APV reduced the extracellular accumulation of all measured purine catabolites during ischemia/reflow and improved to some extent the recovery of the striatal electroencephalographic activity in the majority of the animals. The results suggest that NMDA receptor blockade attenuates acute changes in energy metabolism during ischemia.
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PMID:Blockade of N-methyl-D-aspartate-sensitive acidic amino acid receptors inhibits ischemia-induced accumulation of purine catabolites in the rat striatum. 287 23

Ischemia gives rise to severe energy depletion and influx of Ca from the extracellular space, and it is suggested that increased intracellular Ca leads to the activation of phospholipase C and A, and to liberation of free fatty acids (FFA) in particular arachidonic acid. Phenytoin has been reported not only to maintain the intra- and extracellular cation balance but blockade the Ca channel. The purpose of the present study is to investigate the effect of phenytoin on the liberation of FFA, energy metabolism and mononucleotide metabolism in ischemic brain. Male Wistar rats were subjected to global cerebral ischemia induced by the occlusion of basilar and bilateral common carotid arteries. The brains were frozen in situ by the funnel technique after 5 or 30 min of ischemia or after 10, 30, or 60 min of recirculation following 30 min of ischemia. Purine and pyrimidine nucleotides, FFA, and glycolytic intermediates were measured by HPLC, GLC, and fluoro-enzymatic method. In non-treated rats, ATP reached a nadir after 5 and 30 min of ischemia. Phenytoin significantly attenuated ATP depletion after 5 and 30 min of ischemia. And also E.C. is higher in phenytoin treated rats than in non-treated rats in ischemia. After 60 min of recirculation, ATP recovered to 1.93 +/- 0.02 mumol (72.3% of pre-ischemia) in treated rats but 1.60 +/- 0.07 mumol/g (60% of pre-ischemia) in non treated rats. In E.C., there are significant differences between non-treated and treated rats after 10 and 30 min of recirculation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The effect of phenytoin on free fatty acid liberation and mononucleotide metabolism in transient ischemia]. 321 41

Purine nucleotides, nucleosides, nucleobases, dinucleotides and nucleosides derivatives from acid-extracted rat liver and diaphragm were separated and quantitated by reversed-phase ion-pair high-performance liquid chromatography with a mobile phase composed of 90 mM potassium phosphate, 15 mM tetrabutylammonium hydroxide and a 1-30% methanol gradient. During 5 min of ischemia, adenine and guanine nucleotides decreased along with significant declines in NAD and increases in adenosine, inosine, hypoxanthine, xanthine, NADP and adenylosuccinate. Nitrobenzylthioinosine by gavage (5 mg/kg per day for five days) increased adenosine levels but without any alteration in nucleobase levels. Adenosine was shuttled to every available intracellular reservoir which included in declining order of magnitude GDP greater than adenosylhomocysteine greater than adenosine greater than ADP greater than AMP greater than IMP = XMP = GMP.
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PMID:Demonstration of the adenosine reservoirs with nitrobenzylthioinosine in liver and diaphragm by high-performance liquid chromatography. 339 39

Nucleotide metabolism was studied in rats during and following the induction of 10 min of forebrain ischemia (four-vessel occlusion model). Purine and pyrimidine nucleotides, nucleotides, and bases in forebrain extracts were quantitated by HPLC with an ultraviolet detector. Ischemia resulted in a severe reduction in the concentration of nucleoside triphosphates (ATP, GTP, UTP, and CTP) and an increase in the concentration of AMP, IMP, adenosine, inosine, hypoxanthine, and guanosine. During the recovery period, both the phosphocreatine level and adenylate energy charge were rapidly and completely restored to the normal range. ATP was only 78% of the control value at 180 min after ischemic reperfusion. Levels of nucleosides and bases were elevated during ischemia but decreased to values close to those of control animals following recirculation. Both the decrease in the adenine nucleotide pool and the incomplete ATP recovery were caused by insufficient reutilization of hypoxanthine via the purine salvage system. The content of cyclic AMP, which transiently accumulated during the early recirculation period, returned to the control level, paralleling the decrease of adenosine concentration, which suggested that adenylate cyclase activity during reperfusion is modulated by adenosine A2 receptors. The recovery of CTP was slow but greater than that of ATP, GTP, and UTP. The GTP/GDP ratio was higher than that of the control animals following recirculation.
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PMID:Mononucleotide metabolism in the rat brain after transient ischemia. 370 29


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