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

In a global model of brain ischemia, accumulation of amino acids was studied in the extracellular space of the auditory cortex and the internal capsule using microdialysis, and in CSF of halothane anesthetized cats. In both brain regions, blood flow determined by hydrogen clearance decreased below 10 ml/100 g/min after extracranial multiple-vessel occlusion, and extracellular potassium activity (Ke) measured in the dialysate increased significantly. A delayed rise in Ke was observed in CSF. In contrast, ischemic amino acid accumulation differed markedly between the two brain regions investigated. In cortex, transmitter amino acids glutamate, aspartate, and gamma-aminobutyric acid (GABA) rose almost immediately after onset of ischemia, and increased 30-, 25-, and 250-fold, respectively, after 2 h of ischemia. The nontransmitter amino acids taurine, alanine, and serine increased 10-, seven-, and fourfold, respectively, whereas glutamine and essential amino acids (valine, phenylalanine, isoleucine, and leucine) increased only 1.5-fold. In the internal capsule, increases in amino acids, if any, were delayed and much smaller than in cortex. The largest alteration was a fivefold elevation of GABA. In CSF, changes in amino acids were small and comparable to those in the internal capsule. Our results demonstrate that ischemia-induced extracellular amino acid accumulation is a well localized phenomenon restricted to gray matter structures that possess release and reuptake systems for these substances. We assume that amino acids diffuse slowly into adjacent while matter structures, and into CSF.
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PMID:Ischemia-induced accumulation of extracellular amino acids in cerebral cortex, white matter, and cerebrospinal fluid. 841 67

By studying early postmortem changes in cerebrospinal fluid (CSF) it is possible to draw conclusions as to premortem focal brain cell injury and terminal brain ischemia. Cisternal fluid (CF) from 40 different adult cadavers with no known neurological disorder was analyzed and compared with known in vivo values. They were divided into four groups (n = 10 in each group), CF samples taken 2, 4, 10, and 24 h after death. The enzyme activity of CK and CK-BB (EC 2.7.3.2) increased linearly and statistically significantly 4-24 h postmortem (P < 0.001) the 2 h values being already 10 to 20 times higher than in vivo, LD and its isoenzymes 1 to 3 (EC 1.1.1.27) distinctly 10 to 24 h after death. Glucose and pyruvate concentrations in the CF declined, as did Na+ and Cl-. Lactate and K+ increased over time. The earliest statistically significant changes between different timepoints were seen in lactate, pyruvate and K+ concentrations. The GABA concentration was already more than 170 times at 2 h postmortem, and glutamate more than 20 times higher than in vivo. The concentrations of alanine, glycine, lysine, histidine, isoleucine, phenylalanine, and tyrosine were 2 to 3 times higher at 2 h postmortem than during life. The concentrations of all amino acids and ammonia increased linearly and statistically significantly (P < 0.001) in the CF 4 to 24 h postmortem.
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PMID:Critical evaluation of postmortem changes in human autopsy cisternal fluid. Enzymes, electrolytes, acid-base balance, glucose and glycolysis, free amino acids and ammonia. Correlation to total brain ischemia. 851 12

Although accounting for 2% of body weight, brain has one of the greatest metabolic rates compared with other organs and systems. The energy metabolic consum is expended mainly in the maintenance of ionic gradient, essential to neuronal activity. Brain receives energy substrates from circulation, with interference of blood brain barrier (BBB). Glucose is the main substrate and has a metabolic rate so high as 150 g/day (0.7 mM/G/min). At cellular level, metabolism of glucose seems to be controlled by phosphofructokynase. If the cellular level were high enough, manose and other products like fructose 1,6 biphosphate, pyruvate, lactate and acetate can be used in the place of glucose. Lactate, when oxyded, consums at least 21% of the cerebral needs of O2. In ischemia and inflammatory infections, brain tissue produces lactate instead of use it. Ketone bodies reduce cerebral needs of glucose; in view of the disturbances that occur in cerebral production of succinyl CoA and guanosine 3 phosphate (GTP), they must be considered as complementary substrate but not as an alternative one. Although they can be metabolized, there are no evidences that brain could produce energy from systemic free fatty acids, even when hypoglicemia is present. Ethanol and glycerol are considered only at experimental level. Brain uptake of aminoacids occur better for long chain aminoacids, specially valine. The aminoacids that are synthetised in the brain (aspartate, gluconate and alanine) show the lower absortion rates. All aminoacids should be oxided to CO2 and H2O. Even when glucose consum is reduced to 30%, aminoacid accounts for only 10% of the energetic expenditure of the brain. To maintain cerebral glucose and oxygen supply to the brain, blood flow must be at least 800 ml/min. The regulation of supply and consumption of energy substrate by the brain is changed in few situations. Among them, are included the oxidation of lactate immediately before milk diet early in development and utilization of ketone bodies at the beginning of lactation. This review includes a brief discussion about the relevance of glucose as the main energy substrate for cerebral tissue in different ages and ischemia or hypoxia.
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PMID:[Control of supply and use of energy substrates in the encephalon]. 858 33

The suitability of two-dimensional (2D) proton spectroscopy for monitoring, in vivo, the changes in levels of brain metabolites induced by cerebral ischemia was investigated in an experimental model of 30-min reversible ischemia induced by four-vessel occlusion in the rat. The resulting data were compared with those obtained by one-dimensional (1D) proton and phosphorus spectroscopy. Phosphorus spectra obtained during ischemia showed significant drops in levels of phosphocreatine (-73%), beta-ATP (-60%), and intracellular pH (to 6.30) and an increase in inorganic phosphate level (905%). 1D and 2D proton spectra showed decreases in the N-acetylaspartate/creatine-phosphocreatine ratio that were not significantly different [-21% (1D) and -32% (2D)]. Similarly, the increases in lactate/creatine-phosphocreatine ratio were not significantly different [2,546% (1D) and 3,020% (2D)]. 2D spectroscopy also indicated a decrease in aspartate (-66%) and an increase in the inositol-choline derivative (+124%) pools during ischemia and an increase in alanine pool (+516%) during reperfusion. The glutamate-glutamine pool and taurine content did not change significantly during ischemia but decreased during reperfusion. The glucose level transiently decreased (-67%) during ischemia and increased immediately after (+261%). The levels of all the metabolites investigated returned to control values within 175 min after ischemia. 2D spectroscopy seems to be a reliable method of monitoring the changes in levels of cerebral compounds known to be involved in ischemia.
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PMID:A one-dimensional (proton and phosphorus) and two-dimensional (proton) in vivo NMR spectroscopic study of reversible global cerebral ischemia. 863 74

The aim of this study was to elucidate the mechanisms by which retinal cells release endogenous amino acids in response to ascorbate/Fe(2+)-induced oxidative stress, as compared with chemical hypoxia or ischemia. In the absence of stimulation, oxidative stress increased the release of aspartate, glutamate, taurine, and GABA only when Ca2+ was present. Under hypoxia or ischemia, the release of aspartate, glutamate, glycine, alanine, taurine, and GABA increased mainly by a Ca(2+)-independent mechanism. The increased release observed in N-methyl-D-glucamine+ medium suggested the reversal of the Na+-dependent amino acid transporters. Upon oxidative stress, the release of aspartate, glutamate, and GABA, occurring through the reversal of the Na(+)-dependent transporters, was reduced by about 30%, although the release of taurine was enhanced. An increased release of [3H]arachidonic acid and free radicals seems to affect the Na+-dependent transporters for glutamate and GABA in oxidized cells. All cell treatments increased [Ca2+]i (1.5 to twofold), although no differences were observed in membrane depolarization. The energy charge of cells submitted to hypoxia or oxidative stress was not changed. However, ischemia highly potentiated the reduction of the energy charge, as compared with hypoglycemia or hypoxia alone. The present work is important for understanding the mechanisms of amino acid release that occur in vivo upon oxidative stress, hypoxia, or ischemia, frequently associated with the impairment of energy metabolism.
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PMID:Oxidative stress, hypoxia, and ischemia-like conditions increase the release of endogenous amino acids by distinct mechanisms in cultured retinal cells. 863 76

We investigated changes in vascular reactivity to endothelin (ET) and local release of ET-like immunoreactivity (ET-LI) induced by myocardial ischemia and reperfusion in a pig model of coronary thrombosis and thrombolysis and studied the possible mechanisms producing the changed vascular reactivity to ET-1. We induced coronary thrombosis by inserting a copper coil into the left anterior descending coronary artery (LAD) and achieved thrombolysis with tissue plasminogen activator (t-PA). Vascular reactivity to ET-1 in the nonischemic and ischemic/reperfused LAD diagonal branches was evaluated in vitro. ET-LI was analyzed in plasma from the great cardiac vein and aorta for estimation of local release. The vasoconstrictor response to ET-1 was enhanced twofold (p < 0.01) in the ischemic/reperfused arteries as compared with the nonischemic arteries. The vasoconstriction induced by the ETB receptor agonist [Ala 1,3,11,15] ET-1 or serotonin was not significantly affected by ischemia/reperfusion. The ETA receptor antagonist BQ-123 reversed the ET-1-induced vascular contraction to a similar degree in ischemic/reperfused and control arteries. The ET-1-induced vasoconstriction of control arteries was not affected by inhibition of nitric oxide (NO) synthase with NG-nitro-L-arginine (L-NNA) or cyclooxygenase with indomethacin. During reperfusion, the myocardial venoarterial plasma concentration difference of ET-LI and blood flow increased, resulting in an increased overflow of ET-LI. Our results demonstrate that coronary thrombosis and thrombolysis evokes enhanced local release of ET-LI during the reperfusion period and increases the vasoconstrictor effects of ET-1 through a mechanism related to ETA receptor activation but unrelated to altered endothelial function. These changes may play a role in the development of ischemic/reperfusion injury and no-reflow phenomenon.
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PMID:Myocardial release of endothelin (ET) and enhanced ET(A) receptor-mediated coronary vasoconstriction after coronary thrombosis and thrombolysis in pigs. 863 92

Lactate-edited 1H NMR difference spectra have been acquired from intact rat liver tissue following flushing and preservation in ice. A peak, initially at 1.26 ppm, was seen to increase in the liver tissue with preservation time. This peak was assigned to lactate, despite the fact that its chemical shift was initially shifted by approximately -0.1 ppm relative to an externally added standard. The assignment was based on the following: (a) the peak increased over a 24-h ischemic storage period; (b) it was coupled to a signal 2.78 +/- 0.02 ppm upfield; and (c) a parallel increase in lactate was noted in perchloric acid extracts of tissue from the same liver. An additional peak, assigned to alanine, was also observed during storage and was also shifted by approximately -0.1 ppm. Inclusion of dimethyl sulfoxide, which readily permeates liver tissue, demonstrated that this chemical shift alteration was a tissue-specific effect. These results demonstrate that 1H NMR spectroscopy of intact liver tissue during hypothermic ischemia is possible, though chemical shift assignments should be made with caution.
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PMID:Proton nuclear magnetic resonance spectroscopy of lactate production in isolated rat liver during cold preservation. 867 59

Myocardial regions perfused through a coronary stenosis may cease contracting, but remain viable. Clinical observations suggest that increased glucose utilization may be an adaptive mechanism in such "hibernating" regions. In this study, we used a combination of 13C-NMR spectroscopy, GC-MS analysis, and tissue biochemical measurements to track glucose through intracellular metabolism in intact dogs infused with [1-13C]glucose during a 3-4-h period of acute ischemic hibernation. During low-flow ischemia [3-13C]alanine enrichment was higher, relative to plasma [1-13C]glucose enrichment, in ischemic than in nonischemic regions of the heart, suggesting a greater contribution of exogenous glucose to glycolytic flux in the ischemic region (approximately 72 vs. approximately 28%, P < 0.01). Both the fraction of glycogen synthase present in the physiologically active glucose-6-phosphate-independent form (46 +/- 10 vs. 9 +/- 6%, P < 0.01) and the rate of incorporation of circulating glucose into glycogen (94 +/- 25 vs. 20 +/- 15 nmol/gram/min, P < 0.01) were also greater in ischemic regions. Measurement of steady state [4-13C)glutamate/[3-13C]alanine enrichment ratios demonstrated that glucose-derived pyruvate supported 26-36% of total tricarboxylic acid cycle flux in all regions, however, indicating no preference for glucose over fat as an oxidative substrate in the ischemic myocardium. Thus during sustained regional low-flow ischemia in vivo, the ischemic myocardium increases its utilization of exogenous glucose as a substrate. Upregulation is restricted to cytosolic utilization pathways, however (glycolysis and glycogen synthesis), and fat continues to be the major source of mitochondrial oxidative substrate.
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PMID:Glucose metabolism distal to a critical coronary stenosis in a canine model of low-flow myocardial ischemia. 869 Aug 5

Glucose and energy metabolism in rat liver after ischemic damage was investigated by in vivo 31P NMR spectroscopy, 1H-detected 13C NMR spectroscopy, and in vitro 13C NMR spectroscopy using [1-13C]glucose as a tracer. Arterial ketone body ratio (AKBR; acetoacetate/beta-hydroxybutylate) and oxygen consumption of isolated mitochondria were also examined to evaluate hepatic function. The rats were divided into three groups: (A) without ischemia, (B) 10-min ischemia, and (C) 30-min ischemia. ATP was almost depleted at 10 min of ischemia and recovered after reperfusion, but the recovery was not complete. The recovery after 30-min ischemia was smaller than that after 10-min ischemia. [13C]Glucose was infused immediately after the reperfusion, and in vivo 1H-detected 13C NMR demonstrated sequential glucose incorporation into the liver. However, the incorporation depended on the blood sugar levels and did not reflect hepatic function. In vitro 13C NMR disclosed the glycogen C-1 signal in the nonischemic group and alanine C-3 and lactate C-3 signals in the ischemic groups. The intensity of glycogen was correlated positively (r = 0.648, P = 0.002) and those of alanine and lactate were correlated negatively (r = -0.831, P < 0.005 and r = -0.710, P = 0.005, respectively) to the ATP levels as measured by in vivo 31P NMR. These results suggested that ATP level participates in glycogenesis and gluconeogenesis in the liver. The AKBR and oxygen consumption of isolated mitochondria were the highest in the 10-min ischemia group, which might reflect mitochondrial compensatory response to the decreased ATP level.
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PMID:Glucose and energy metabolism in rat liver after ischemic damage assessed by 13 C and 31 P NMR spectroscopy. 876 41

Periods of ischemia followed by reperfusion of the ischemic tissue are associated with myocardial damage and ventricular arrhythmia. Angiotensin converting enzyme inhibitors limit the occurrence of these arrhythmias. The protective effects of angiotensin converting enzyme inhibitors may be due to inhibition of bradykinin (BK) degradation, rather than inhibition of angiotensin II formation. Other enzymes which catabolize BK include the endopeptidases EP24.11 and EP24.15. The purpose of this study was to determine if inhibitors of EP24.11 and EP24.15 decrease ischemia/reperfusion injury and if this protection is mediated by BK receptors. Rabbits were anesthetized and prepared for recording of cardiovascular parameters. The chest was opened and a left ventricular artery occluded for 30 min, followed by a 2-hr reperfusion period. Infarct size was determined using triphenyl tetrazolium chloride staining immediately after reperfusion. The enzyme inhibitors, ramiprilat, N-[1-(R,S)-carboxy-3-phenylpropyl]-Phe-pAB, and N[1-(R,S)-carboxy-3-phenylpropyl]-Ala-Ala-Phe-pAb, singly and in combinations were administered 3 min before reperfusion. Compared to saline (32.1 +/- 2.1), ramiprilat (18.3 +/- 2.8) and the EP inhibitors (14.4 +/- 1.4 for the combination) significantly decreased infarct size, with the greatest decrease occurring when all three inhibitors were combined (10.6 +/- 1.5). The protective effect of the EP inhibitors was blocked by the BK2 receptor antagonist, HOE 140 (30.1 +/- 2.6). Enzyme assays demonstrated EP24.11 and EP24.15 in the rabbit heart. We conclude that the EP inhibitors decreased ischemia/reperfusion injury by protecting BK from metabolism and that a combination of inhibitors provides superior protection to that given by a single agent.
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PMID:Endopeptidase inhibitors decrease myocardial ischemia/reperfusion injury in an in vivo rabbit model. 881 83


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