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

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

Glutamate is an important factor in the mechanisms of neuronal damage following cerebral ischemia. Blockade of one type of glutamate receptor, the N-methyl-D-aspartate (NMDA) receptor, decreases brain infarct size in experimental models of permanent focal ischemia, but protection in models of transient reversible ischemia is ambiguous. We investigated the effect of the noncompetitive NMDA receptor antagonist dizocipiline (MK-801) on neuronal damage in the CA1 region of the rat hippocampus, using two models of reversible cerebral ischemia: 10 or 15 min of bilateral common carotid occlusion combined with hypotension, or 6-8.5 min of cardiac arrest. Histopathologic evaluation of neuronal damage was performed 7 days after the ischemic insults. Thirteen groups of rats (a total of 129 animals) were treated with saline or dizocilpine in single or multiple doses ranging from 0.1 to 5 mg.kg-1, given intravenously or intraperitoneally prior to and/or after the ischemic insult. In none of the dizocilpine-treated groups could neuronal protection be demonstrated in the CA1 region of the septal as well as dorsotemporal hippocampus, compared to a corresponding saline-treated group. We conclude that systemically administered noncompetitive NMDA receptor antagonists do not provide a marked protection against neuronal damage after a transient period of severe forebrain ischemia.
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PMID:Lack of protection by the N-methyl-D-aspartate receptor blocker dizocilpine (MK-801) after transient severe cerebral ischemia in the rat. 185 15

Although considerable evidence supports a role for excitatory amino acids in the pathogenesis of ischemic neuronal injury, few in vivo studies have examined the effect of increasing durations of ischemia on the extracellular concentrations of these agents. Recently, other neurotransmitters (e.g., glycine and dopamine) have been implicated in the mechanism of ischemic neuronal injury. Accordingly, this study was undertaken to examine the patterns of changes of extracellular glutamate, aspartate, glycine concentrations in the hippocampus, and dopamine, serotonin, and dopamine metabolites in the caudate nucleus with varying durations (5, 10, or 15 minutes) of transient global cerebral ischemia as evidence to support their pathogenetic roles. Microdialysis was used to sample the brain's extracellular space before, during, and after the ischemic period. Glutamate and aspartate concentrations in the dialysate increased from baseline by 1-, 5-, and 13-fold and by 4-, 9-, and 31-fold, respectively, for the three ischemic durations. The concentrations returned to baseline rapidly after reperfusion. The peak concentrations of glutamate and aspartate were significantly higher with increasing ischemic duration. Dopamine concentrations increased by approximately 700-fold in response to all three ischemic durations and returned to baseline within 10 min of reperfusion. Glycine, in contrast, increased during ischemia by a mean of 4-fold, but remained elevated throughout the 80-min period of reperfusion. The final concentrations of glycine were significantly higher than baseline levels (p = 0.0002, Mann-Whitney test). That glutamate and aspartate concentrations in the hippocampus co-vary with the duration of global ischemia is taken as supportive evidence of their pathogenetic role in ischemic neuronal injury.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Changes in extracellular concentrations of glutamate, aspartate, glycine, dopamine, serotonin, and dopamine metabolites after transient global ischemia in the rabbit brain. 189 10

Excitatory amino acids have been implicated in the production of calcium mediated neuronal death following central nervous system ischemia. We have used microdialysis to investigate changes in the extracellular concentrations of amino acids in the spinal cord after aortic occlusion in the rabbit. Glutamate, aspartate, glutamine, asparagine, glycine, taurine, valine, and leucine were measured in the microdialysis perfusate by high pressure liquid chromatography. The concentrations of glutamate, glycine, and taurine were significantly higher during ischemia and reperfusion than controls. Delayed elevations in the concentrations of asparagine and valine were also detected. The elevation of glutamate is consistent with the hypothesis that excitotoxins may mediate neuronal damage in the ischemic spinal cord. Increased extracellular concentrations of asparagine and valine may reflect preferential use of amino acids for energy metabolism under ischemic conditions. The significance of increased concentrations of inhibitory amino acid neurotransmitters is unclear.
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PMID:Spinal cord ischemia-induced elevation of amino acids: extracellular measurement with microdialysis. 197 91

Glutamate, an excitatory amino acid (EAA), plays an important role in neuron to neuron signaling by binding to specific receptors. When, during neuronal firing, quanta of glutamate are released from the nerve terminal, they interact with the receptors for a few milliseconds and, thereafter, glutamate is promptly cleared by appropriate mechanisms. The neurotoxic action of glutamate arises from its capacity to trigger a pathophysiological chain of events when it acts continuously and abusively on its receptors (e.g., during cerebral edema associated with trauma, ischemia, stroke). In primary cultures of cerabellar granule neurons the abusive stimulation of EAA receptors by glutamate amplifies pathologicaly two early intracellular signals: free cytosolic Ca++ and the translocation of protein kinase C (PKC) from cytosol to neuronal membrane. Both of these signals persist unabated even after removal of glutamate from the incubation medium. Natural gangliosides and their semisynthetic derivatives protect neurons from glutamate toxicity by blocking the consequences of receptor abuse but they leave physiological responses to glutamate unaffected; hence they represent a prototype of a "receptor abuse dependent antagonist" (RADA).
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PMID:Ganglioside-mediated protection from glutamate-induced neuronal death. 198 78

Glutamate is an important excitatory amino acid at many central nervous system synapses. After its release from presynaptic nerve terminals, glutamate transiently binds to specific neuronal membrane receptors, which transduce its signal by the generation of intracellular second messengers before being rapidly cleared from the synapse. However, during ischemia, the glutamate concentration at synapses surrounding the focal lesion can be increased for sustained periods of time, resulting in abusive stimulation of glutamate receptors that can eventually be neurotoxic. To develop drugs capable of selectively blocking the pathological effects of glutamate in neurons surrounding ischemic lesions while leaving the physiological actions of glutamate in nonlesioned areas of the brain unaffected, it is essential to delineate glutamate-induced intracellular events that are specific to receptor abuse. This article describes the intracellular sequelae of physiological and pathological glutamate receptor activation and suggests potential targets for such receptor abuse-dependent antagonists (RADAs).
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PMID:Abusive stimulation of excitatory amino acid receptors: a strategy to limit neurotoxicity. 216 13

Glutamate is the putative neurotransmitter of several clinically important pathways, including cortical association fibers, corticofugal pathways such as the pyramidal tract, and hippocampal, cerebellar, and spinal cord pathways. The excitatory actions of glutamate are mediated by multiple, distinct receptor types and potent receptor antagonists have recently been developed. Glutamate also has neurotoxic properties and can produce "excitotoxic" lesions reminiscent of human neurodegenerative disorders. Abnormally enhanced glutamatergic neurotransmission may cause excitotoxic cell damage and lead to the neuronal death associated with olivopontocerebellar atrophy, Huntington's disease, status epilepticus, hypoxia/ischemia, and hypoglycemia. Pharmacologic manipulation of the glutamatergic system may have great potential for the rational treatment of a variety of neurologic diseases.
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PMID:The role of glutamate in neurotransmission and in neurologic disease. 242 40

Glutamate, the major excitatory neurotransmitter of the brain, mediates neuronal injury from hypoxia-ischemia, hypoglycemia, and status epilepticus. Drugs that block glutamate receptors, particularly the N-methyl-D-aspartate (NMDA) receptor, protect neurons from these insults. Noncompetitive antagonists of NMDA receptors have the potential to prevent perinatal neurologic morbidity.
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PMID:Role of excitatory amino acids in brain injury caused by hypoxia-ischemia, status epilepticus, and hypoglycemia. 254 4

Glutamate, a major excitatory transmitter substance, is neurotoxic at high concentrations. Brain dialysis experiments have demonstrated an extracellular overflow of glutamate during ischemia, and there is good evidence from several animal models that glutamate antagonists offer partial protection against the development of ischemic cell degeneration. These and other experimental data indicate that glutamate may be involved in the pathogenesis of ischemic brain damage. Quantitative immunocytochemical investigations carried out in the authors' laboratory suggest that ischemia is associated with loss of glutamate from nerve cell bodies, and reduced ability of the glial cells to metabolize glutamate. We discuss possibilities of new therapeutic strategies.
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PMID:[New aspects of the pathogenesis of ischemic brain damage. Possible involvement of excitatory amino acids]. 257 68

Excitatory dicarboxylic amino acid neurotransmitters, particularly glutamate, have been implicated in mediating neuronal cell injury in brain ischemia-anoxia, epilepsy, and stroke. Glutamate neurotoxicity has been demonstrated in several in vitro models, as well as its prevention by a variety of agents, including several sialic acid-containing glycosphingolipid species, gangliosides. We have now examined ganglioside effects in anoxic exposed cultures of granule cells from Postnatal Day 8 rat cerebellum. Cells between 10 and 12 days in vitro were placed into an anoxic atmosphere or subjected to a chemical model of anoxia by a pulse exposure to rotenone. Widespread neuronal degeneration of neuronal cell bodies and their associated neurite network was seen the following day. These effects on cell vitality at the morphological level were quantitatively confirmed by measuring the photometric reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide to a blue formazan product. This neuronal injury was abolished by the specific N-methyl-D-aspartate receptor noncompetitive antagonists Mg2+, phencyclidine and MK-801, suggesting that this subtype of glutamate receptor is involved in the pathogenesis of anoxic granule cell injury. Pretreatment for 30 to 60 min or more or concurrent treatment with ganglioside GM1 largely prevented the ensuing neuronal death (ED50 = 25 microM), even 4 days later. Degeneration induced by exogenous glutamate was equally reduced. Asialo GM1 (lacking sialic acid) was ineffective. These results are consistent with the observed beneficial effects of the gangliosides in ischemic brain injury models in vivo.
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PMID:Monosialoganglioside GM1 protects against anoxia-induced neuronal death in vitro. 268 18


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