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

Since only little xanthine oxidase (XO) activity in mammalian brain was detected in earlier reports, the major end product of AMP degradation in the brain has been believed to be hypoxanthine. Our recent experimental study however, has indicated the presence of uric acid in the rat brain subjected to focal ischemia or cold injury. Allopurinol, a xanthine oxidoreductase inhibitor, has been found to markedly suppress the uric acid production in the same experimental settings. These results suggested that uric acid is generated from hypoxanthine by enzymatic reaction in injured brain tissue. The aim of this experiment is to prove the existence of xanthine oxidoreductase activity in brain tissue. Xanthine oxidoreductase activity in rat cerebral tissue was measured immediately or at 24-hour after decapitation. Under pentobarbital anesthesia, twenty Sprague-Dawley rats were killed by decapitation following washout of the blood by trans-cardiac perfusion with cold physiological saline. Immediately or after 24 hours of decapitation ischemia, the forebrain was removed and homogenized in 6 ml ice cold 0.05 M potassium phosphate buffer (pH 7.8) containing 1 mM phenylmethylsulfonyl fluoride, 0.3 mM EGTA, and 10 mM dithiothreitol. The homogenate was centrifuged at 100,000 g for 60 min and then the supernatant was dialyzed overnight against 0.05 M potassium phosphate buffer (pH 7.8). Aliquot of each dialyzed supernatant (sample) and standard xanthine solution with NAD was reacted at 37 degrees C for 15 min to measure the combined activity of xanthine dehydrogenase (XDH) and XO. For the measurement of XO, standard xanthine solution without NAD was used.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Xanthine oxidoreductase activity in rat brain tissue: the changes after decapitation]. 280 24

In this lecture, evidence is presented to support the following hypothesis regarding the roles of xanthine oxidase-derived oxidants and granulocytes in ischemia-reperfusion-induced microvascular injury. During the ischemic period, ATP is catabolized to yield hypoxanthine. The hypoxic stress also triggers the conversion of NAD-reducing xanthine dehydrogenase to the oxygen radical-producing xanthine oxidase. During reperfusion, molecular oxygen is reintroduced into the tissue where it reacts with hypoxanthine and xanthine oxidase to produce a burst of superoxide anion and hydrogen peroxide. In the presence of iron, superoxide anion and hydrogen peroxide react via the Haber-Weiss reaction to form hydroxyl radicals. This highly reactive and cytotoxic radical then initiates lipid peroxidation of cell membrane components and the subsequent release of substances that attract, activate, and promote the adherence of granulocytes to microvascular endothelium. The adherent granulocytes then cause further endothelial cell injury via the release of superoxide and various proteases.
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PMID:Role of xanthine oxidase and granulocytes in ischemia-reperfusion injury. 305 26

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

Thirty minutes of warm hepatic ischemia produced by portal triad cross-clamping was repeated five times at 30-minute intervals in three groups of five dogs each: Group A was subjected only to portal triad cross-clamping; Group B received simultaneous clamping of the celiac axis and the superior mesenteric artery; and Group C had a simultaneous splenojugular shunt. The arterial blood ketone body ratio (acetoacetate/beta-hydroxybutyrate: KBR), reflecting the NAD+/NADH ratio in liver mitochondria, decreased significantly after each cross-clamping in all groups. After the first declamping, there was no significant difference in the recovery rate of the KBR among the three groups. After the second declamping, the recovery rate in Group A decreased significantly compared with the rates of Groups B and C (P less than 0.05). After the fourth declamping, the recovery rate in Group B was significantly lower than that of Group C (P less than 0.05). The hepatic energy charge [(ATP + 1/2ADP)/(ATP + ADP + AMP)] 30 minutes after the fifth declamping decreased significantly to 0.75 +/- 0.01 in Group A, compared with 0.84 +/- 0.01 in Group C (P less than 0.01). The lactate and total free plasma amino acid levels in the arterial blood increased significantly in the order of Groups A, B, and C. It is suggested that the inflow of stagnant portal venous blood to ischemic liver impairs hepatic energy metabolism.
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PMID:Deleterious effects of splanchnic congestion on hepatic energy metabolism following repeated portal triad cross-clamping in dogs. 319 65

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

Xanthine oxidase activities of pig myocardium and blood during and following myocardial ischemia were measured using HPLC, and electrochemical detection of hypoxanthine, xanthine and uric acid. Myocardial ischemia was produced by occluding the anterior descending coronary artery two-thirds of the way from its origin. There was no accumulation of either xanthine or urate in the ischemic pig myocardium during occlusion periods of 90 min, but there was a substantial accumulation of hypoxanthine. Similarly, there was no increase in myocardial xanthine or urate during the 30 min reperfusion following coronary artery occlusion periods of 15, 30, 60 or 90 min. Following in vitro incubation at pH 8 of myocardial homogenates or blood with either hypoxanthine or xanthine and NAD, no urate production was detectable. In contrast, significant amounts of xanthine and/or urate were produced, following addition of xanthine oxidase to the reaction mixtures. Additional in vitro experiments showed that the following pig tissues were lacking xanthine oxidase activity: left and right atrial appendage, left and right ventricle, interventricular septum, anterior descending and circumflex coronary arteries, ascending aorta, lung, and blood. Large amounts of xanthine oxidase (9.3 +/- 1.8 SEM mU/g wet weight, n = 7) were found in pig liver. In the ischemic pig heart, transmural infarction developed within 60 min of ischemia. Ventricular arrhythmias and fibrillation occurred most frequently within 45 min of ischemia and within seconds after reperfusion. These results showed that the pig heart and blood were xanthine oxidase deficient, suggesting that xanthine oxidase-derived free oxygen radicals were not involved in the cytotoxic and arrhythmogenic effects brought about by myocardial ischemia and/or reperfusion in the pig.
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PMID:Arrhythmias and infarction in the ischemic pig heart are not mediated by xanthine oxidase-derived free oxygen radicals. 342 28

The enzyme xanthine: acceptor oxidoreductase found in rat heart equilibrates between three forms differing in electron acceptor specificity. Form D transfers electrons exclusively to NAD+ and accounts for 85% of total oxidoreductase activity. Form O transfers electrons to molecular oxygen and accounts for 8%. The D/O form prefers NAD+, but without NAD+ transfers electrons to oxygen. Interconversion from D to O and O to D forms is catalyzed by sulfhydryl group-modifying reagents: Cd2+, Cu2+, disulfiram, and heating with dithiothreitol. This suggests that sulfhydryl groups participate in the first stage of enzyme conversion. The NADH/NAD+ concentration ratio may regulate the dehydrogenase activity of xanthine:acceptor oxidoreductase (NAD+-dependent activity of D and D/O forms). Accumulating NADH inhibits hypoxanthine hydroxylation. The amount of form O increases during cardiac ischemia, facilitating superoxide radical-ion generation. Also, NADH/NAD+ does not regulate form O, promoting adenylate nucleotide pool depletion, especially in the heart which has low de novo purine nucleotide synthesis.
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PMID:Three forms of xanthine: acceptor oxidoreductase in rat heart. 346 36

To assess the applicability of phosphorus-31 magnetic resonance spectroscopy (31P-MRS) in the analysis of renal transplant viability and preservation techniques with respect to pre-transplant ischemia, we studied two rat groups. Twenty-five rat kidneys were subjected to various time increments of warm ischemia (Group A), and 31P-MRS was performed on each kidney at time intervals of up to 72 hours during simple hypothermic storage. We correlated findings of 31P-MRS with simultaneous findings of electron microscopic (EM) ultrastructural viability parameters (in Group A) and subsequent survival and renal function in 30 rats (Group B) subjected to similar amounts of variable ischemia. Intracellular phosphorus metabolite levels were nondestructively monitored by 31P-MRS via spectral peaks of NAD, sugar monophosphates (SP), and inorganic phosphate (Pi). We concluded: SP/Pi and NAD/Pi ratios decay in a time-dependent manner for both warm and cold ischemia, although this process is much slower during cold storage; EM viability parameters correlate with the development of acute tubular necrosis (irreversible damage) versus nonviability (gross cell death) on a qualitative basis only; and 31P-MRS enables a quantitative assessment of renal viability and ischemic renal damage and can predict the degree of acute tubular necrosis and post-ischemic renal function. 31P-MRS is potentially a noninvasive, nondestructive method of assessing viability during simple hypothermic storage of the rat kidney. Preliminary evidence shows that this MRS method can be applied to human kidney viability studies for clinical renal transplantation and urologic research concerning renal preservation.
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PMID:Assessment of renal viability by phosphorus-31 magnetic resonance spectroscopy. 351 65

Mitochondrial function was examined in cats after 1 h of complete cerebral ischemia and subsequent recirculation periods from 15 min to 56 h. During ischemia the NAD-linked respiratory control ratio and the maximal phosphorylation capacity of "free" and synaptosomal mitochondria decreased to 53% to 76% of control values. During postischemic reperfusion to 6 h, mitochondrial function was restored to 80%, remaining less than control throughout the entire investigated recirculation period with a tendency of secondary deterioration from 12 h of reperfusion onward. ADP: O ratios were unaffected during ischemia, but decreased significantly during early recirculation (15 to 30 min), and were completely restored from 45 min reperfusion onward. Correlation with electrophysiologic recordings revealed that mitochondrial dysfunction was not a limiting factor for neurophysiologic recovery during early recirculation (15 to 90 min). When the recirculation period was extended (greater than 3 h), good neurophysiologic recovery was associated with a return of mitochondrial function to control levels; inversely, poor mitochondrial function was correlated with poor neurophysiologic recovery.
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PMID:Mitochondrial respiration during recirculation after prolonged ischemia in cat brain. 356 58

Brain levels of NADH and NAD+ were measured in three models of cerebral ischemia to determine whether degradation of the pyridine nucleotides is enhanced in models that generate high concentrations of lactic acid. Complete ischemia (decapitation), in which lactate increased to 14 mmol/kg, caused a gradual decrease in the NAD pool to 50% of control by 2 h. During focal ischemia (occlusion of the middle cerebral artery), the decrease in the NAD pool was less pronounced (82% of control at 2 h) despite the accentuated accumulation of lactate to 33 mmol/kg. In a third model (unilateral hypoxia-ischemia), pretreatment of animals with glucose augmented the ischemic elevation of lactate from 30 mmol/kg to 40 mmol/kg and greatly impaired restoration of energy metabolites during recirculation. However, glucose pretreatment had no effect on the size of the NAD pool during ischemia or early recovery. These results, therefore, demonstrate that the pyridine nucleotide pool is not rapidly degraded during ischemic insults that accumulate high concentrations of lactic acid. The stability of the NAD pool may have been enhanced by the limited increase in brain levels of NADH that occurred in these models of incomplete ischemia.
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PMID:Effect of lactacidosis on pyridine nucleotide stability during ischemia in mouse brain. 361 29


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