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)

A uniform, predictable pattern of cellular abnormalities is seen after complete, irreversible ischemic injury to the central nervous system. This is in contrast to the heterogeneous, multifocal picture which characterizes incomplete ischemia. The range of abnormalities in neuronal soma after an arterial occlusion changes considerably as a function of time and site. There is no single pattern of neuronal alteration that can be ascribed exclusively to ischemia. Red neurons are a relatively late (about 18 h) indicator of ischemia and are seen only in areas where blood supply is marginal. In addition to depletion of high-energy-phosphate reserves, brain ischemia results in characteristic alterations of amino acid concentrations in the ischemic tissue. Glutamate, glutamine, and aspartate either decrease or remain constant while alanine increases. Proportional decreases in the former three amino acids may be explained by simple dilution due to edema. Increases in alanine relative to glutamate and aspartate may be utilized as a biochemical index of perfusion to various brain regions.
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PMID:Neuronal ischemic injury: light microscopy, ultrastructure and biochemistry. 9 17

After the middle cerebral artery of rats was occluded, changes in the content of 14 free amino acids and the activity of antioxidant enzymes in the ischemic striatum were assessed with respect to the duration of ischemia. Glu and Asp levels were significantly reduced by 60 min of ischemia, GABA was increased by 30 and 60 min and Ala was increased by 5, 15, and 30 min. During ischemia, the levels of striatal Gln, Asn, Ser, Tau, Gly and Pro were found to be normal. In comparison with the sham-operated rats, the changes in the content of Thr, His, Arg and Tyr were inconclusive, since the effect of operative stress could not be ruled out on such occasion. Concomitantly, the Zn-Cu superoxide dismutase and glutathione peroxidase activity were significantly reduced by 30 min of ischemia. It revealed that the reduced capacity to scavenge the oxygen free radicals occurred during the early stage of cerebral ischemia. The above changes of Glu, Gln, GABA and Pro level might be considered as the final outcome of the decrease of glutamate synthesis, the acceleration of its conversion to GABA, and the extracellular leakage of glutamate. According to our data, the oxygen free radicals might be involved in the evolution of primary neuronal damage at the ischemic striatum.
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PMID:[Mechanism of neuronal damage caused by cerebral ischemia]. 133 25

Renal metabolism has been studied in eight dogs before and 48 hr after a 60-min period of renal ischemia induced by clamping the left renal artery with the simultaneous removal of the right kidney, and in 12 sham-operated animals. The study involved the measurement of renal uptake and production of lactate, glutamine, glutamate, alanine, ammonium, and oxygen, and the measurement of the tissue concentrations of ATP, glutamine, lactate, alpha-ketoglutarate, aspartate, and alanine in the renal cortex. Two days after a temporary renal ischemia, the remaining kidney showed a 22% decrease in glomerular filtration rate (GFR) and a 25% decrease in renal plasma flow. Fractional sodium and potassium excretions were similar to those of control dogs. Renal production or extraction of glutamine, glutamate, alanine, ammonium, and oxygen (all expressed by 100 ml of GFR) was not significantly different in basal conditions or 2 days after ischemia, but lactate extraction was reduced in postischemic kidneys (-101 +/- 29 vs -204 +/- 38 mumol/100 ml GFR in control dogs). The cortical concentrations of glutamine and glutamate were lower in postischemic than in control kidneys. No differences were found in cortical concentration of alpha-ketoglutarate, aspartate, lactate, pyruvate, or ATP, but total nucleotides and inorganic phosphate were decreased in postischemic kidneys. It is concluded that in the recovery phase of the ischemia, a decreased lactate uptake is the main metabolic change, and total ATP production is adapted to the decrease of GFR and sodium reabsorption.
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PMID:Renal cortical intermediary metabolism in the recovery phase of postischemic acute renal failure in the dog. 153 34

University of Wisconsin solution is currently recognized as the best solution for long-term organ preservation. It is recommended that UW solution be used as the in situ flush prior to organ explantation. The purpose of our study was to determine if hepatic allograft function was impaired by flushing the graft in situ with Euro-Collins and later flushing the graft ex vivo with UW solution, prior to cold storage. Fifty-six donors were randomly assigned to either an EC (n = 24) or UW (n = 32) in situ flush. The livers flushed with EC in situ were later flushed with 1 L of UW on the back table and stored in UW solution. Livers flushed with UW in vivo were similarly flushed and stored in UW on the back table. Concerning the donor allograft, there was no statistical difference (P greater than 0.05) between groups in sex, race, blood type, arterial anatomy, age, prothrombin time (PT), partial thromboplastin time (PTT), total bilirubin (TBR), direct bilirubin (DBR), aspartate amino transferase (AST), or alanine amino transferase (ALT). In addition, the recipients were compared for differences in sex, race, blood type, preoperative status, number of rejections, recipient age, length of surgery, and ischemia time and patient survival. There was no significant difference between groups (P greater than 0.05). There was no significant difference in patient survival (P = 0.238). Values for TBR, AST, ALT, PT, PTT, and AP were collected immediately preoperatively and postoperatively and on postoperative days 1, 3, 7, 14, and 28. There was no difference between groups in these values (P greater than 0.05). In our study there was no difference between the groups with respect to graft performance. This would justify the use of EC as an in situ flush during solid organ procurement and flushing with UW solution on the back table with an estimated savings of $400 to $1200 per procurement.
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PMID:A prospective randomized trial between Euro-Collins and University of Wisconsin solutions as the initial flush in hepatic allograft procurement. 158 93

Coronary artery disease causes an increase in glutamate uptake and alanine output by the heart. We assessed the effects of acute myocardial ischemia on alanine and glutamate exchange and ammonia production in 10 anesthetized open-chest domestic swine (46.9 +/- 0.7 kg). Coronary blood flow was controlled through an extracorporal perfusion circuit. After a nonischemic control period (aerobic) the blood flow in the left anterior descending coronary artery was reduced by 60%. Arterial and anterior interventricular venous samples where drawn before and during 35 min of ischemia. Subendocardial blood flow, measured using radiolabeled microspheres, decreased from 1.27 +/- 0.16 to 0.25 +/- 0.09 (ml/g)/min, and left-ventricular wall-thickening fell to 47% of aerobic values. Ischemia resulted in a significant increase in the rate of glucose uptake (p less than 0.05) and a switch to net lactate production (p less than 0.01). Ischemia did not affect the rates of alanine output (-0.9 +/- 1.0 vs. -0.3 +/- 0.3 mumol/min) or glutamate uptake (-0.4 +/- 1.1 vs. 0.3 +/- 0.6 mumol/min), but did increase the venous-arterial difference for ammonia (-4.1 +/- 4.1 to 52.7 +/- 5.5 microM, p less than 0.0001) and the ammonia output (-0.33 +/- 0.24 to 1.34 +/- 0.14 mumol/min, p less than 0.0001). In conclusion, acute ischemia did not stimulate greater alanine output or glutamate uptake. However, acute ischemia did cause an increase in anaerobic glycolysis rate and ammonia output, which reflects a profound disruption in myocardial energy metabolism.
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PMID:Alanine, glutamate, and ammonia exchanges in acutely ischemic swine myocardium. 159 Jul 40

Excitatory amino acids (EAAs) have been implicated to play a part in the development of hypoxic-ischemic brain injury in the neonate. The aim of the present study was to follow changes of intra- and extracellular (microdialysis) amino acids in the cerebral cortex in a model where cortical hypoxic-ischemic damage is produced consistently. Hypoxic-ischemia (unilateral ligation of the carotid artery + 2 h of exposure to 7.8% oxygen) caused a depletion of tissue ATP, phosphocreatine and glucose with a concomittant accumulation of AMP and lactic acid in cortical tissue. These changes were accompanied by a decrease of tissue aspartate and glutamine whereas the contents of gamma-aminobutyric acid (GABA), phenylalanine, leucine, isoleucine, valine and alanine increased. In the extracellular fluid GABA, glutamate, aspartate, taurine, glycine and alanine all increased multi-fold during hypoxic-ischemia. Aspartate and glutamate returned to near initial levels 2 h after the end of the insult, whereas the elevation of glycine persisted during recovery. In conclusion, the high extracellular levels of EAAs and glycine may exert injurious effects during and after hypoxic-ischemia.
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PMID:Intra- and extracellular changes of amino acids in the cerebral cortex of the neonatal rat during hypoxic-ischemia. 178 36

We used in vivo microdialysis to determine the impact of a focal hypoxic-ischemic insult on striatal amino acid efflux in the immature brain. Microdialysis probes were inserted into the right striatum of postnatal day 7 rats. To induce hypoxic-ischemic injury, the right carotid artery was ligated and the animals were exposed to 8% oxygen for 2.5 hours (n = 22). Rats exposed to ligation alone (n = 10) or hypoxia alone (n = 8) and untreated controls (n = 17) were also studied. Two hours after probe insertion, a 30-minute baseline microdialysis sample was obtained. After arterial ligation, two additional baseline samples were collected. Five more samples were collected over the next 2.5 hours (in 8% oxygen or room air). Eight amino acids (glutamate, aspartate, taurine, glutamine, alanine, serine, glycine, and asparagine) were consistently detected in dialysates using a high-performance liquid chromatography assay with electrochemical detection. In untreated controls, amino acid efflux did not change over 4 hours. During hypoxia-ischemia, efflux values fluctuated widely, with marked intra-animal and interanimal variability. Efflux peaks for each amino acid were defined as values greater than the highest control mean value plus two standard deviations. Glutamate efflux peaks (greater than 7 pmol/min compared with 2 pmol/min at baseline) were detected in no controls and in eight hypoxic-ischemic rats (p = 0.006, Fisher's two-tailed exact test). Taurine efflux peaks (greater than 75 pmol/min compared with 10 pmol/min for controls at baseline) were detected in 10 hypoxic-ischemic rats and one control (p = 0.01) and in seven of the eight animals in which glutamate efflux peaks occurred (p = 0.006).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of perinatal stroke on striatal amino acid efflux in rats studied with in vivo microdialysis. 185 13

The effects of glutamate on anginal threshold, cardiac metabolism and hemodynamics were studied in 11 patients with stable angina pectoris, positive stress test results, and pacing-induced myocardial lactate release due to coronary artery disease (CAD) (n = 9) or syndrome X (n = 2). Data were obtained before, during and after 2 identical periods of coronary sinus pacing, the second being preceded by an intravenous injection of monosodium glutamate 1.2 (n = 7) or 2.5 (n = 4) mg/kg body weight. After glutamate administration, pacing time to onset of angina increased from mean +/- standard deviation 103 +/- 53 to 166 +/- 71 seconds (p less than 0.01) and ST-segment depression after pacing decreased from 2.3 +/- 1.0 to 1.6 +/- 1.1 mm (p less than 0.01). Arterial glutamate concentration increased 60% (p less than 0.01) after the low dose and 150% (p less than 0.01) after the high dose of glutamate. Regardless of dose, myocardial glutamate uptake increased by 25% (p less than 0.01). Pacing-induced cardiac release of lactate diminished 50% (p less than 0.05), whereas the releases of xanthine and hypoxanthine were unchanged by glutamate. Arterial free fatty acids decreased 20% (p less than 0.01). Circulating levels and cardiac exchanges of alanine, glucose and citrate were unchanged. Glutamate did not influence heart rate, arterial blood pressure, coronary blood flow, coronary vascular resistance or myocardial oxygen consumption. One patient complained of short-lasting burning sensations after receiving the high glutamate dose. In conclusion, augmented provision of glutamate enhances pacing tolerance in stable angina, presumably by a metabolic improvement of cardiac energy production during ischemia.
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PMID:Antiischemic and metabolic effects of glutamate during pacing in patients with stable angina pectoris secondary to either coronary artery disease or syndrome X. 185 69

We have induced acute renal failure (ARF) in barbiturate anesthetized rabbits, through warm ischaemia of 30 or 60 min duration caused by transient bilateral occlusion of renal arteries. In this model we have monitored some renal performance parameters, before and 4 hours after reperfusion, aiming to characterize ARF in this animal species. Glomerular filtration rate (determined by the inulin clearance technique) was of 9.74 +/- 0.48 ml min-1 in 4 rabbits before injury and declined by 91% (60 min ischemia) during the first reperfusion hour. In 6 rabbits undergoing 30 min occlusion, pre-ARF values of 10.70 +/- 0.98 ml min-1 declined by 47%. In both groups no recovery was observed in the following hours. Tubular enzymes (alanine-amino-peptidase, AAP and N-acetyl-beta-glucosaminidase, NAG) were released into urines before injury at the rate of 1.11 +/- 0.18 and 1.32 +/- 0.41 mU min-1, respectively, in the 30 min model (3 animals/group). During ARF, maximal AAP output was five-fold increased (5.83 +/- 0.35 mU min-1), whereas NAG was unmodified. On the other hand, renal haemodynamics in 5 rabbits did not change after the ischaemic procedure: total renal blood flow (44 +/- 5 ml min-1) and renal vascular resistances (225 +/- 26 Pa ml-min) displayed less than 10% variations throughout the reperfusion period. We concluded that ARF in rabbits can be reliably and reproducibly monitored and that the pathogenesis of the disease, in our situation, is attributable mainly to tubular cell damage and not to impairment of the vascular component of renal performance.
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PMID:[Parameters of tubulo-glomerular function in anesthetized rabbits with acute kidney insufficiency]. 197 49

It is well established that excitatory amino acid neurotransmitters are extensively liberated during ischemia and that they have neurotoxic properties contributing to neuronal injury. To study changes in the liberation of excitatory and other amino acids during cerebral ischemia, we measured their extracellular concentrations and related them to blood flow levels and electrophysiologic activity (electrocorticogram and auditory evoked potentials) before and for up to 2 hours after multiple cerebral vessel occlusion in 14 anesthetized cats. Blood flow levels between 0 and 43 ml/100 g/min were reached. Concentrations of the excitatory amino acid neurotransmitters increased most (aspartate 10-fold, glutamate 30-fold, and gamma-aminobutyric acid 300-fold compared with control values) below a blood flow threshold of 20 ml/100 g/min. The total power of the electrocorticogram and the amplitude of the auditory evoked potentials were affected below the same blood flow threshold. In contrast, concentrations of the nontransmitter amino acids taurine, alanine, asparagine, serine, and glutamine increased 1.5-5-fold as blood flow decreased, while concentrations of the essential amino acids phenylalanine, valine, leucine, and isoleucine did not change during cerebral ischemia. The great increases in concentrations of the excitatory amino acid neurotransmitters below a blood flow threshold close to that for functional disturbance is in accordance with the role of these amino acids in ischemic cell damage. Their release at blood flow levels compatible with cell survival and the increase in their concentrations with severity and duration of cerebral ischemia imply that excitotoxic antagonists may have potential as therapeutic agents.
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PMID:Differences in ischemia-induced accumulation of amino acids in the cat cortex. 197 18


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