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

The exchange of purines in liver and active skeletal muscle with short-term exhaustive exercise was investigated. Eight male subjects performed two similar 10-min bouts of exhaustive supine cycling, separated by 75 min of rest. Immediately after termination of the second bout, a tourniquet was applied to the upper part of the thigh for 10 min. After the first bout, the arterial concentration of hypoxanthine and uric acid increased from 4.1 +/- 0.3 (SE) to a peak value of 36.3 +/- 7.9 mumol/l (P < 0.05) and from 335 +/- 23 to a peak value of 421 +/- 28 mumol/l (P < 0.05), respectively. There was a net release of hypoxanthine from the muscle at 12 and 45 min postexercise and an uptake of hypoxanthine and inosine in the liver at 7 and 42 min postexercise. Uric acid was released from the liver at 7 and 42 min after exercise. Before the second exercise bout and at 2 and 10 min after the release of the tourniquet, there was a significant net uptake of uric acid by the muscle. The present study demonstrates that, after strenuous short-term exercise, the main source of plasma hypoxanthine is the muscle, with no net contribution of this purine from the liver. Hypoxanthine in the blood is taken up by the liver where most of it is converted to uric acid. After exercise and a short period of ischemia, uric acid is taken up by the muscle.
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PMID:Exchange of purines in human liver and skeletal muscle with short-term exhaustive exercise. 830 59

The aim of the study was to determine the pathways and site of adenosine triphosphate (ATP) catabolism during lung ischemia, which thus far are largely unknown. For this purpose we used the isolated rabbit lung. Rabbit lungs were flushed in situ with a modified Krebs-Henseleit solution (60 ml/kg), the deflated heart lung blocks were isolated, immersed in saline solution, and stored at 37 degrees C. In group I (normothermic ischemia; n = 6) tissue content of ATP decreased progressively from 9.42 +/- 0.58 mumol/g dry wt to 3.42 +/- 0.24 mumol/g dry wt after 30 min of ischemia and further to 0.51 mumol/g dry weight after 4 h. Hypoxanthine was the major catabolite (92% of the nucleoside and purine base fraction at 4 h ischemia). Adenosine did not accumulate (preischemic 0.08 +/- 0.02 mumol/g dry weight vs. 0.13 +/- 0.01 mumol/g dry weight; P > 0.05). AMP accumulated, but also inosine monophosphate (IMP), which was undetectable before ischemia, increased significantly during ischemia. To determine the breakdown pathway of AMP, 400 microM of the adenosine deaminase inhibitor EHNA was added to the flush solution in group II (n = 6). During ischemia, ATP breakdown was unaltered but adenosine became the major catabolite (2.8 times the concentration of hypoxanthine at 4 h ischemia). By pretreatment of the rabbits with the nucleoside transport inhibitor R 75231 (group III; n = 6) no effect was observed on the concentrations during ischemia of inosine and hypoxanthine and only a minor increase of adenosine was found. Cytochemical localization of nucleoside phosphorylase revealed activity predominantly in the endothelial cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenine nucleotide degradation in ischemic rabbit lung tissue. 847 63

Xanthine dehydrogenase (XDH) and xanthine oxidase (XO) are enzymes involved in the metabolism of purines in various organisms. XO produces superoxide radicals, suggesting that is responsible for tissue ischemia-reperfusion injury. To test this notion further studies were performed on rat kidneys and the time course of changes in purine nucleotides, oxypurines and XDH and XO activity was determined. At 24 hours after reperfusion subsequent to 30-minute ischemia, serum creatinine increased to 0.83 +/- 0.74 mg/dl from 0.28 +/- 0.06 mg/dl (the level prior to ischemia, the control). Renal ATP and ADP contents were reduced after ischemia lasting for 30 minutes and restored 10 minutes after reperfusion following 30 minutes of ischemia. The renal AMP content increased after 30 minutes of ischemia and recovered within 10 minutes after reperfusion. The total adenine nucleotide (TAN) content was reduced gradually during ischemia-reperfusion in the rat kidney. Although the energy charge was reduced following 30 minutes of ischemia, it was restored to the control level 10 minutes following reperfusion. Hypoxanthine (HX) and xanthine (X), which had accumulated at 30 minutes after ischemia, were reduced to the control levels 10 minutes after reperfusion. There were no significant changes in the pre-ischemia values of total XDH and XO activities or XDH/XO ratio during the period nor at various time intervals (up to 24 hours) during reperfusion. It was shown that HX and X accumulate without significant conversion of XDH to XO during ischemia. Therefore the putative role of XO in ischemia-reperfusion injury seems to more complex than initially predicted.
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PMID:[The role of xanthine dehydrogenase (xanthine oxidase) in ischemia-reperfusion injury in rat kidney]. 901 77

Lactate accumulation, amino acid aspartate and glutamate levels, and hypoxanthine, xanthine and malondialdehyde (MDA) concentrations were compared in neonate rat brain after transient global hypoxia induced alone or in association with unilateral ligation of a carotid artery. Lactate production in both hemispheres was higher in cerebral hypoxia-ischemia (CHI) than in cerebral hypoxia (CH), and was lower in CHI after 2 h than at 15 min of recovery. Aspartate and glutamate levels were reduced 15 min after CHI in both hemispheres, but aspartate alone was decreased 2 h after CHI in the ipsilateral (left) hemisphere and 15 min after CH in both hemispheres. Hypoxanthine was increased 15 min after CHI in the ipsilateral hemisphere but decreased at 2 h, whereas xanthine was increased. MDA production was not modified after CH or CHI. These data, compared to those obtained in adult animals suggest that glutamate release and the capacity to generate oxygen-derived radicals are lower in neonates after ischemia. These differences might explain why the brain of the mammalian neonate is much more resistant to CH and CHI than that of the adult.
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PMID:Changes in excitatory amino acid levels and tissue energy metabolites of neonate rat brain after hypoxia and hypoxia-ischemia. 948 82

Ischemia leads to impaired ATP metabolism, with increased production of purine degradation products, such as hypoxanthine and xanthine, which are useful markers of tissue hypoxia. These extracellular markers of ischemia have been studied extensively in many clinical conditions of oxidative stress, including perinatal asphyxia, acute respiratory distress syndrome, cerebral ischemia, and preeclampsia. The aim of this study was to explore the usefulness of urinary hypoxanthine and xanthine as ischemia markers in acute coronary syndromes. Urinary excretion of hypoxanthine and xanthine was assessed by high-performance liquid chromatography in 30 patients with acute coronary syndromes and in 30 age- and sex-matched controls. Serum and urine uric acid, creatinine, and urea concentrations were also determined. Hypoxanthine excretion was significantly elevated in patients compared with healthy controls (84.37+/-8.63 and 42.70+/-3.97 nmol/mg creatinine, mean+/-SEM, P<0.0001). Urinary xanthine levels were also increased in patients with acute coronary syndromes (100.13+/-12.14 and 34.74+/-4.07 nmol/mg creatinine patients and controls, respectively; P<0.0001). Hypoxanthine and xanthine excretion showed a strong positive correlation in both groups. Significant negative correlations between urinary hypoxanthine and uric acid and xanthine and uric acid were observed in the patients, but not in controls. In conclusion, increased levels of ATP degradation products hypoxanthine and xanthine are observed in various hypoxic clinical conditions. This study suggests that these parameters may be useful markers of ischemia in patients with acute coronary syndromes.
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PMID:Urinary hypoxanthine and xanthine levels in acute coronary syndromes. 1078 78

A transition zone between well-perfused proximal tissue and inadequately perfused distal tissue was evaluated histologically and biochemically in skin flaps. Cranially based pedicle flaps, 3 x 7.5 cm, were made on the backs of female Sprague-Dawley rats. Flap survival was 22% of the original flap area at 7 days and 40% at 14 days after flap elevation (p < 0.001). The transition zone consisted of full-thickness skin survival proximally and partial-thickness wound distally. It is evident that skin wounds induced by ischemia or reperfusion repair continuously between 7 and 14 days after flap elevation. Tissue glucose, lactate, and hypoxanthine levels were measured to assess capillary perfusion in the transition zone on postoperative day 3. The proximal full-thickness skin 5 mm from the wound margin demonstrated no significant changes in glucose and lactate levels compared with normal skin. The partial-thickness wounds exhibited no change in glucose (a 33% decrease was not statistically significant) but a significant increase (319% of normal) in lactate level (p < 0.05). Hypoxanthine levels increased to 453% of normal in full-thickness skin (p < 0.01) and to 787% in partial-thickness wounds (p < 0.001). Metabolic response was evaluated by enzyme assays in the transition zone. Hexokinase activity increased by 251% of normal (p < 0.05), glucose 6-phosphate dehydrogenase by 245% (p < 0.01), and glutathione reductase by 184% (p < 0.05) in the proximal full-thickness skin. Hexokinase activity further increased by 482% of normal (p < 0.01), glucose 6-phosphate dehydrogenase by 379% (p < 0.05), and glutathione reductase by 346% (p < 0.01) in partial-thickness wounds. The results suggest that partial-thickness wounds have less capillary circulation but greater antioxidant enzyme activities than does the survival area with full-thickness skin.
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PMID:Microanalyses of enzymes and metabolites in ischemia/reperfusion-induced partial-thickness skin wounds. 1716 2

Marine mammals are exposed to ischemia/reperfusion and hypoxia/reoxygenation during diving. During oxygen deprivation, adenosine triphosphate (ATP) breakdown implies purine metabolite accumulation, which in humans is associated with pathological conditions. Purine recycling in seals increases in response to prolonged fasting and ischemia. Concentrations of metabolites and activities of key enzymes in purine metabolism were examined in plasma and red blood cells from bottlenose dolphins (Tursiops truncatus) and humans. Hypoxanthine and inosine monophosphate concentrations were higher in plasma from dolphins than humans. Plasma hypoxanthine-guanine phosphoribosyl transferase (HGPRT) activity in dolphins suggests an elevated purine recycling rate, and a mechanism for avoiding accumulation of non-recyclable purines (xanthine and uric acid). Red blood cell concentrations of hypoxanthine, adenosine diphosphate, ATP and guanosine triphosphate were lower in dolphins than in humans; adenosine monophosphate and nicotinamide adenine dinucleotide concentrations were higher in dolphins. HGPRT activity in red blood cells was higher in humans than in dolphins. The lower concentrations of purine catabolism and recycling by-products in plasma from dolphins could be beneficial in providing substrates for recovery of ATP depleted during diving or vigorous swimming. These results suggest that purine salvage in dolphins could be a mechanism for delivering nucleotide precursors to tissues with high ATP and guanosine triphosphate requirements.
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PMID:Plasma Hypoxanthine-Guanine Phosphoribosyl Transferase Activity in Bottlenose Dolphins Contributes to Avoiding Accumulation of Non-recyclable Purines. 2737 92

Ischemia-reperfusion injury(IRI), described as tissue damage caused by reversible ischemic injury or hypoxia prior to the blood supply restoration, is a common pathological phenomenon. In recent study, a hypoxia-reoxygenation (H/R) in the presence or absence of propofol posthypoxia treatment (P-PostH) cell model was built to simulate the condition of IRI, and researchers found propofol may protect cells by suppressing autophagic cell death. To investigate the mechanism underling the protective effect of propofol. A metabolomic analysis was performed in this study using ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF- MS) to compare the metabolism during the process of H/R in the presence or absence of P-PostH. A total of 22 metabolites were detected varied after propofol posthypoxia treatment. Pathway analysis revealed these metabolites were mainly involved in the purine metabolic pathway, three carboxylic acid metabolic pathways, alanine, aspartate and glutamate metabolism pathway and lipid metabolism pathway. We measured the level of Hypoxanthine to verify the metabolomics work, for pathway analysis, we detect the level of reactive oxygen species with H/R and P-PostH treatment. Our study achieved a global comparison of metabolism profiling of H/R cell model with or without propofol posthypoxic treatment. The result indicated that propofol can attenuate endothelial injury caused by IRI by reducing oxidative damage.
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PMID:Protective effect of propofol on ischemia-reperfusion injury detected by HPLC-MS/MS targeted metabolic profiling. 2980 30


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