Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

2D COSY 1H NMR with surface coil has been used to resolve and assign cerebral metabolites which had previously been detected but could not be resolved or assigned in situ in the living animal by conventional 1D 1H NMR. A wide range of cerebral metabolites, including alanine, N-acetyl aspartate, aspartate, choline derivatives, creatine/phosphocreatine pool, GABA, glucose, glutamate/glutamine pool, inositol, lactate and taurine were simultaneously resolved and assigned in situ in the whole animal using the 2D COSY correlation graphs. Global irreversible ischemia caused the appearance and the disappearance of cross-peaks in the 2D COSY 1H NMR map, corresponding to increases in alanine, GABA and lactate and glucose depletion.
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PMID:2D COSY 1H NMR: a new tool for studying in situ brain metabolism in the living animal. 235 67

Rats with a portacaval anastomosis and ligation of the hepatic artery 2 days later were infused for 6 hr with a 10% glucose solution (group I) or the same solution combined with 0.24 M/liter branched-chain amino acids (BCAA, group II). Control animals with portacaval anastomosis and sham-operation (group III) or two sham-operations (group IV) were infused with a 10% glucose solution. The rats were killed by decapitation and indoleamines and amino acids were determined in the brain. Rats with liver ischemia were stuporous at the end of the experiment irrespective of treatment. The concentrations in the cortex of lysine, methionine, phenylalanine, threonine, alanine, glutamine, glycine, histidine, and tyrosine were significantly increased in group I compared to group IV. Infusion of BCAA to rats with liver-ischemia (group II) resulted in significantly lower concentrations of lysine, methionine, phenylalanine, threonine, histidine and tyrosine and increased concentrations of isoleucine, leucine, valine, and arginine compared to group I. The content of serotonin in the cortex and brain stem was significantly increased in group I compared with the BCAA-treated animals (group II) and the control groups III and IV. The concentrations of 5-hydroxyindoleacetic acid (5-HIAA) in the cortex and brain stem were higher in group I than in group IV. Infusion of BCAA to rats with liver ischemia normalized the concentrations of 5-HIAA in the cortex and brain stem.
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PMID:Amino acids and indoleamines in the brain after infusion of branched-chain amino acids to rats with liver ischemia. 242 87

The present study investigated the conversion of amino acids to succinate and the contribution of this pathway to anaerobic energy production during regional ischemia in the dog heart in situ. The relation between regional myocardial blood flow, estimated by the tracer microsphere technique, and myocardial contents of metabolites (glutamate, alanine, succinate, lactate) as well as their local arterio-venous differences (A-V) were determined. During 30 min of coronary artery occlusion, myocardial glutamate decreased from 2.3 mumol/g wet wt in control tissue to 1.2 mumol/g wet wt in severely ischemic areas, while aspartate was unaffected. Myocardial alanine increased in a 1: 1 stoichiometry compared to glutamate, and succinate accumulated. During control perfusion (118 mmHg), A-V of lactate, succinate and glutamate were +470, -0.7 and -3.9 nmol/ml, respectively. Stepwise reduction of perfusion pressure led to the release of lactate and succinate from the underperfused area; extraction of glutamate occurred at the lowest perfusion pressure investigated (34 mmHg; A-V: -500, -10.4 and +4.2 nmol/ml, respectively). The data indicate that during regional ischemia in vivo, succinate is synthetized exclusively from glutamate via 2-oxo-glutarate, following transamination with glycolytic pyruvate yielding alanine, while the contribution of aspartate is negligible. Using tissue levels of glutamate and lactate together with the local arterio-venous concentration differences of these compounds, it can be estimated that degradation of glutamate delivers 20% of the ATP generated by substrate level phosphorylation reactions. Thus energy production by the glutamate degradation pathway is significant in vivo under conditions of flow deprivation.
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PMID:Glutamate degradation in the ischemic dog heart: contribution to anaerobic energy production. 256 82

The effect of low flow ischemia and subsequent reperfusion with 5.5 mM glucose or 5 mM acetate on energy metabolism and catabolism of myocardial glutamate and aspartate was studied in isolated perfused guinea pig hearts. Reperfusion with acetate was followed by low recovery of the cardiac contractile function associated with a great rise in isovolumic end-diastolic pressure. It was combined with more profound losses of tissue adenine nucleotides and the total Cr compared to reperfusion with glucose. The total glutamate and aspartate pool decreased more than two-fold compared to the initial one regardless of substrate. However, glutamate content was reduced by 58 and 38% with acetate and glucose, respectively. The expenditure of both amino acids was caused by alanine formation stimulated by glycolysis/glycogenolysis. The remaining glutamate and aspartate pool in the reperfused hearts positively correlated with adenine nucleotides (r = 0.62), the total creatine (r = 0.65), and the recovery of contractile function (r = 0.64). The results suggest that the glutamate and aspartate pool may be of critical importance for postischemic functional and metabolic recovery of the heart.
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PMID:Association of myocardial glutamate and aspartate pool and functional recovery of postischemic heart. 257 52

Anginal threshold and cardiac metabolism during infusion of glucose, 350 mg/min, were compared with control values before, during, and after pacing in nine patients with coronary artery disease (CAD) and nine patients without coronary artery disease (non-CAD). Pacing induced no ischemia in non-CAD patients; in CAD patients, intolerable angina developed in less than 5 minutes. However, glucose infusion in the latter group increased the time to onset of angina (110 +/- 24 seconds before infusion versus 140 +/- 24 seconds following infusion) and decreased the extent of ST segment depression (1.8 +/- 0.3 mm before infusion versus 0.9 +/- 0.2 mm following infusion, p less than 0.01) following pacing. In all subjects, arterial levels and cardiac uptake of glucose rose by 100% (p less than 0.001) and those of free fatty acids fell by 50% (p less than 0.01). Arterial lactate and uptake of lactate by nonischemic myocardium increased by 30% (p less than 0.05). During pacing in CAD patients, this elevated uptake was outweighed by similar increases of lactate release from ischemic areas, leaving mean negative global exchanges unaltered. In CAD patients solely, rebuilding of cardiac glycogen after pacing was suggested from augmented citrate efflux in the control period but not during glucose infusion, suggesting a glycogen-sparing effect. Arterial concentrations and net cardiac fluxes of oxygen, glutamate, and alanine remained unaltered. In conclusion, beneficial effects of glucose during ischemia are associated with increased aerobic and anaerobic glycolysis, saving of glycogen, and decreased lipolysis.
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PMID:Antianginal and cardiac metabolic effects of low-dose glucose infusion during pacing in patients with and without coronary artery disease. 266 29

To assess the effects of insulin in stable coronary artery disease (CAD), 2 U i.v. insulin was given to 9 control and 10 CAD patients during coronary sinus catheterization. Hemodynamic and metabolic data were obtained before and for 90 min after insulin injection. Insulin induced no changes in heart rate, mean aortic pressure, rate-pressure product, coronary sinus flow, or coronary resistance. Metabolic changes were similar in both groups and included 1) 30% decrease of arterial glucose (P less than .001) and 3-fold increase of myocardial glucose uptake (P less than .001), 2) 1.5- to 2.5-fold elevation of arterial lactate (P less than .001) and myocardial lactate usage (P less than .001), respectively, 3) 50-70% suppression of arterial levels (P less than .001) and myocardial uptake of free fatty acids (P less than .01), and 4) 10% reduction of myocardial net oxygen consumption (P less than .05). Myocardial citrate efflux increased in the CAD patients (P less than .05), whereas alanine release rose only in control patients (P less than .01), suggesting that glucose enters glycogen production in the CAD patients and pyruvate production in the control patients to a high degree. Myocardial glutamate uptake remained unchanged. In conclusion, insulin sensitivity was not altered in CAD. The insulin-induced shift from myocardial free fatty acid to carbohydrate usage may be beneficial to the ischemic heart by increasing glycogen stores, saving oxygen, and inhibiting an excess free-fatty acid concentration, which may be toxic during ischemia.
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PMID:Cardiac metabolic and hemodynamic effects of insulin in patients with coronary artery disease. 267 Jun 46

The human heart in the fasting state extracts FFA, glucose, lactate, pyruvate, and ketone bodies from the systemic circulation. Of these substrates, FFA utilization accounts for the greater part of oxygen consumption and energy production. The oxidative use of lipid (FFA) and carbohydrate (glucose and lactate) fuels is reciprocally regulated through the operation of Randle's cycle. Feeding, by increasing both insulin and glucose concentration, shifts myocardial metabolism towards preferential carbohydrate usage, both for oxidative energy generation and for glycogen synthesis. During conditions of reduced oxygen supply, the oxidation of all substrates is decreased while anaerobic metabolism is activated. In patients with coronary artery disease and stable angina pectoris, lactate release in the CS can be demonstrated during pacing stress. However, this occurs in only 50% of patients, and no relationship can be demonstrated between lactate production and the severity of ischemia. In patients with chronic angina, a significant release of alanine in the CS and an increased myocardial uptake of glutamate could be demonstrated at rest and following pacing. These two phenomena result from increased transamination of excess pyruvate to alanine with glutamate serving as NH2 donor. In addition, release of citrate (a known inhibitor of glycolysis) in the CS can be demonstrated following pacing in patients with stable angina. The introduction of PET has made it possible to study regional myocardial perfusion and metabolism in humans noninvasively. Two basically different patterns of myocardial glucose utilization have been observed in patients with coronary artery disease studied at rest using 18F-flurodeoxyglucose. In patients with stable angina on exercise but studied at rest, regional myocar- dial glucose utilization was homogeneously low and comparable with that of a group of normals. In contrast, in patients with unstable angina, myocardial glucose utilization at rest was increased even in the absence of symptoms and ECG signs of acute ischemia. In patients with stable angina, a prolonged increase in glucose uptake could be demonstrated in the post-ischemic myocardium in the absence of perfusion abnormalities, and a state of chronic metabolic ischemia is proposed. PET imaging has also allowed prospective differentiation between viable and nonviable segmental function in patients with recent myocardial infarction and in those undergoing coronary artery surgery; in both cases viable segments have relatively maintained glucose uptakes, whereas nonviable segments have depressed glucose uptakes.
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PMID:Myocardial metabolism in ischemic heart disease: basic principles and application to imaging by positron emission tomography. 268 79

Proton nuclear magnetic resonance (NMR) spectroscopy of perchloric acid tissue extracts has been used to follow serial postischemic changes in the levels of metabolites in the hippocampus, cerebellum, frontal lobes, and parietal/occipital lobes in a rat model of short-duration (10 minutes) forebrain ischemia. Shortly (10 minutes, 1 hour) after the ischemic insult, the levels of the amino acids alanine and gamma-aminobutyric acid are elevated and that of glutamate is depressed in all regions except the cerebellum. The levels of these species return to control values by 24 hours postischemia. No changes are observed in the levels of aspartate or N-acetylaspartate. Greatly elevated levels of acetate 10 minutes postischemia, particularly in the hippocampus, may be due in part to metabolic degradation of fatty acids released due to membrane breakdown. Elevated levels of lactate persist for up to 7 days postischemia, suggesting that normal mitochondrial functioning is not fully restored following the ischemic insult.
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PMID:Nuclear magnetic resonance study of regional metabolism after forebrain ischemia in rats. 271 4

The aim of this study was to measure changes in the extracellular fluid (ECF) concentration of lactate, pyruvate, purines, amino acids, dopamine, and dopamine metabolites in the striatum of rats subjected to focal cerebral ischemia, using intracerebral microdialysis as the sampling technique. Microdialysis probes were inserted into the lateral part of the caudate-putamen bilaterally 2 h before the experiment. Ischemia was induced by permanent middle cerebral artery occlusion (MCAO) on the left side. Microdialysis samples were analyzed by high performance liquid chromatography. Following MCAO, the concentration of lactate, adenosine, inosine, and hypoxanthine rose markedly in the ECF on the occluded side, while there was no significant change in pyruvate. These changes were accompanied by dramatically elevated levels of aspartate, glutamate, taurine, gamma-aminobutyric acid, and dopamine. There was also a marked increase in alanine/tyrosine, while minor or no changes occurred with other amino acids. Concomitantly, the ECF level of the dopamine metabolites 3,4-dihydroxyphenylacetate and homovanillic acid decreased. There was no significant increase in any of the metabolites measured on the right, nonoccluded side. In relation to the concept of excitotoxicity in brain ischemia, it is concluded that during the acute stage of focal cerebral ischemia, the ECF is flooded with both potentially harmful (e.g., aspartate, glutamate, and DA) and protective (e.g., taurine, GABA, and adenosine) agents. The relative importance of these events for the development of cell death in the ischemic penumbra needs to be elucidated. In addition, lactate, inosine, and hypoxanthine, measured in the ECF by intracerebral microdialysis, may prove to have diagnostic and/or prognostic value in neurometabolic monitoring of the ischemic brain.
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PMID:Dynamics of extracellular metabolites in the striatum after middle cerebral artery occlusion in the rat monitored by intracerebral microdialysis. 277 32

The effect of intravenous glutamic acid infusion (3 mg/kg/min) was studied during myocardial ischemia and reperfusion in anesthetized dogs. Left ventricular ischemia was induced by underperfusion of the anterior descending and circumflex coronary arteries. Glutamic acid reduced the ischemic contractile depression 2 min after a 60%-reduction of the coronary blood flow. The left ventricular systolic pressure was decreased by 9% versus 22%, dP/dt by 16% versus 29%, left ventricular systolic pressure heart rate product by 16% versus 31%. Reperfusion with glutamic acid improved the recovery of cardiac performance without any increase in myocardial oxygen consumption. Glutamic acid infusion resulted in a 2-fold augmentation of glutamate uptake by the ischemic myocardium. It led to cessation of ammonia release by the heart due to activation of glutamine synthesis, enhancement of alanine formation coupled with pyruvate utilization and did not change lactate production. The mechanisms of the protective action of glutamic acid are discussed.
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PMID:[Correction of contractile function and metabolism in canine ischemic myocardium due to exogenous glutamic acid]. 286 92


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