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

Glutamate uptake was measured in primary rat cortical astrocyte cultures exposed to sodium azide, 2,4-dinitrophenol, or antimycin A to assess the ability of astrocytes to function under hypoxic conditions. Uptake was maintained at 54-63% of control values despite maximal inhibition of oxidative ATP production. In contrast, the glycolytic inhibitor sodium fluoride (20 mM) reduced glutamate uptake by more than 95% when glucose was the only available substrate. These data suggest that glutamate uptake is largely maintained during hypoxia provided glucose remains available. Astrocyte glutamate uptake may aid neuronal survival during conditions such as incomplete ischemia where oxygen but not glucose is depleted.
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PMID:Astrocyte glutamate uptake during chemical hypoxia in vitro. 136 5

The concentration of fibroblast growth factor (FGF), which is found in cerebrospinal fluid (CSF), markedly increases after the start of feeding. Food intake was dose-dependently suppressed by picomole doses of FGF and facilitated by anti-FGF antibody. This suppression was caused by activation of protein kinase C in glucose-sensitive neurons in the lateral hypothalamus. In situ hybridization by use of cDNA showed that acidic (a)FGF was produced in ependymal cells. The ependymal cells released aFGF by responding to glucose increase in CSF after feeding. Released aFGF diffused into the brain parenchyma and was taken by neurons. Passive avoidance was significantly more reliable after aFGF infusion into CSF. Clamping cerebral arteries in the gerbil induced ischemia, which damaged neurons in the CA1 layer of the hippocampus. Pretreatment with aFGF prevented this damage. Thus, aFGF is not only the most potent substance yet found for the suppression of feeding, but it is also extremely effective as a neurotrophic and memory facilitating substance.
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PMID:A new brain glucosensor and its physiological significance. 137 Feb 49

The effects of plain ischemia (34 degrees C) and the protective role of hypothermia (20 degrees C) alone or in combination with cardioplegia (St Thomas' Hospital [STH] or glucose-potassium-nifedipine [GPN]) on the intracellular kinetics of the activator calcium of cardiac muscle were quantified and compared from the interval-force behaviour (mechanical restitution) of right and left ventricles of the perfused rat heart. Plain ischemia caused a major depression in the restitution of force of contraction of both ventricles, deranged the mixed linear-exponential functions by significantly increasing the time constants of the fitted mechanical restitution curves (MRC) and altered the control right/left ventricle interval-force relationship. The right ventricle was found to be more susceptible to ischemic damage than the left ventricle, and its inotropic reserve was virtually abolished by 1 h of plain ischemia. Hypothermic preservation during ischemia improved the mechanical restitution, salvaged the inotropic reserve and optimized right/left ventricle interval-force relationship, but the time constants of the fitted MRCs were still prolonged. However, both the cardioplegic formulations were equally effective in normalizing the time constants of the fitted curves. In general, right ventricle functions were better preserved by STH cardioplegia and left ventricle functions were better preserved by GPN cardioplegia. Cardioplegic interventions did not further improve the ventricular inotropic reserve compared with hypothermic preservation. Additional beneficial effects of cardioplegic formulations were directed towards stabilizing the linear-exponential functions and hence restitution of force of contraction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intracellular kinetics of the activator calcium of rat heart after ischemic arrest and cardioplegia: quantitative comparison of right and left ventricles. 137 92

The oxidative metabolic rate may be disproportionately high compared with contractile function in postischemic reperfused myocardium. To study the potential involvement of intracellular calcium transport in high energy expenditure after reperfusion, we determined in isolated rat hearts the effect of ruthenium red, an inhibitor of mitochondrial calcium transport, on recovery of contractile function and oxidative metabolic rate. Hearts subjected to 60 minutes of no-flow ischemia exhibited, at 15 minutes after the onset of reperfusion, poor recovery of left ventricular pressure development to only 7% of the corresponding value measured in control hearts (p less than 0.01). However, myocardial oxygen consumption was recovered to 84% of control (p = NS). The ratio of isovolumic contractile performance (expressed as the product of heart rate and left ventricular pressure development) to myocardial oxygen consumption was severely depressed to 6% of control (p less than 0.01). Supplementation of the perfusate with 6 microM ruthenium red during the initial 40 minutes of reperfusion resulted in a reduction of myocardial oxygen consumption to 65% of the value measured after 15 minutes of reperfusion in hearts reperfused without ruthenium red (p less than 0.01), despite a threefold increase of left ventricular pressure development (p less than 0.05). Oxidation of both palmitate and glucose was reduced to a comparable extent by ruthenium red. The ratio of contractile performance to myocardial oxygen consumption increased progressively during infusion of ruthenium red and did not differ further from control hearts after 30 minutes of reperfusion. Cumulative myocardial release of creatine kinase was reduced by 47% (p less than 0.05) in hearts reperfused with ruthenium red-containing medium. The results provide circumstantial evidence for the hypothesis suggesting that enhanced energy expenditure by intracellular calcium transport may be involved in the mechanisms underlying the dissociation between left ventricular performance and myocardial oxidative metabolic rate early after postischemic reperfusion.
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PMID:Dissociation between contractile function and oxidative metabolism in postischemic myocardium. Attenuation by ruthenium red administered during reperfusion. 137 92

The N-methyl-D-aspartate (NMDA)-sensitive subtype of glutamate receptor, which gates Ca(2+)-permeable ion channels, is known for its role in learning and memory formation, in the induction of long-term potentiation, and also in seizure activity and neurotoxicity. In primary cultures of cerebellar neurons, agonists of NMDA receptors induce a dose-dependent release of [3H]arachidonic acid ([3H]AA), which is potentiated by activation of the glycine-positive modulatory site and inhibited by NMDA receptor antagonists. NMDA receptor-induced [3H]AA release is inhibited by quinacrine and partially depends on the presence of extracellular calcium. The [3H]AA release is not sensitive, however, to pretreatment with pertussis or cholera toxin, which suggests a Ca(2+)-dependent activation of phospholipase A2 not employing G proteins. Pretreatment of cultures with the natural and semisynthetic sphingolipids GT1b and PKS 3, respectively, inhibits NMDA receptor-mediated [3H]AA release. We also demonstrated glutamate-evoked [3H]AA release from rat hippocampal slices, which is NMDA receptor mediated, calcium dependent and sensitive to quinacrine. Arachidonic acid and its metabolites have been shown to play a role as second messengers and to modulate neuronal activity. Moreover, they are thought to act as transsynaptic modulators in the mechanism of NMDA receptor-induced long-term potentiation in the hippocampus. Their role in ischemic brain pathology has also been postulated. Our experiments on cultured cerebellar granule cells, incubated in a Mg(2+)-free medium deprived of glucose and oxygen, demonstrated a time-dependent stimulation of [3H]AA release. This release was inhibited by antagonists of NMDA receptors and by quinacrine. Stimulation of NMDA-sensitive glutamate receptors and the subsequent calcium-mediated activation of phospholipase A2 may play a role in the in vivo release of arachidonic acid during brain ischemia. This hypothesis is supported by the observation that the enhanced level of thromboxane B2 in the gerbil brain after 5 min of global ischemia is reduced by the systemic application of either the NMDA antagonist MK-801 or the ganglioside GM1.
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PMID:NMDA receptor-mediated arachidonic acid release in neurons: role in signal transduction and pathological aspects. 138 78

Metabolic disturbances in the canine liver during warm ischemia by Pringle's method for 60 minutes and the role of Coenzyme Q10 (CoQ10), Prostaglandin E1 (PGE1) and ONO-3708, TXA2 receptor antagonist, were studied. Mongrel dogs were divided into five groups; control group, group of liver ischemia without drugs, groups of liver ischemia with CoQ10, PGE1 and ONO-3708 pretreatment. Metabolic rates of PGI2, TXA2, insulin, glucagon and glucose and production of lipid peroxides in the five groups were measured at the points before Pringle's procedure, 5 minutes, 60 minutes and 120 minutes after declamping. In the group of ischemia without drug administration, the hepatic metabolism of PGI2, TXA2, insulin and glucose were decreased after declamping. The metabolism of glucagon, however, was not disturbed by warm ischemia. The production of lipid peroxides increased at 5 minutes after declamping. In the groups of CoQ10, PGE1 and ONO-3708 pretreatment, changes of PGI2, TXA2 and insulin metabolism in the liver were improved, and an increased production of lipid peroxides by warm ischemia was normalized. This study suggests that CoQ10, PGE1 and ONO-3708 protect liver damage by warm ischemia as results of improvement of metabolic disturbances of PGI2, TXA2, insulin and suppression of lipid peroxides production.
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PMID:[Assessment for protective effects of CoQ10, PGE1 and TXA2 receptor antagonist (ONO-3708) on warm ischemic liver]. 138 60

Focal brain ischemia was produced in halothane-anesthetized Mongolian gerbils by occluding the right common and the left external carotid artery. Ninety minutes after vascular occlusion the following regional hemodynamic and metabolic parameters were evaluated in adjacent cryostat sections taken from seven different coronal planes of each brain: cerebral blood flow (CBF), glucose utilization (CMRG), and the tissue content of ATP and glucose. NADH fluorescence was recorded from the surface of the cryostat block. In addition, tissue slices were taken from each brain to determine the rate of phosphorylation of 2-deoxyglucose in ischemic and nonischemic regions. Depending on the density of ischemia, the following metabolic disturbances were observed. At CBF values below 35 ml x 100 g-1 x min-1 CMRG increased and at values below 25 ml x 100 g-1 x min-1 it declined sharply. Glucose content declined when CBF was below 35 ml x 100 g-1 x min-1 and ATP fell at CBF below 20 ml x 100 g-1 x min-1. At 10 ml x 100 g-1 x min-1 ATP was completely depleted. NADH fluorescence was found elevated at flow rates that caused an increase of glucose utilization and was maximal when CBF stopped. The ischemic thresholds for the initial increase in CMRG and the complete depletion of ATP content represent the metabolic equivalent of the penumbra zone and provide a basis for the evaluation of therapeutic procedures for the treatment of stroke.
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PMID:Threshold relationship between cerebral blood flow, glucose utilization, and energy metabolites during development of stroke in gerbils. 139 69

In spontaneously diabetic BB rats, the effect of chronically maintained blood glucose levels on the degree of energy failure and brain pH change during an ischemic insult, and on subsequent recovery after reperfusion, was studied with in vivo 31P magnetic resonance spectroscopy. Short duration forebrain ischemia (10-min carotid occlusion plus hypotension of 50 mmHg) was induced in diabetic and nondiabetic male BB rats whose blood glucose levels were maintained with insulin. Spectra were obtained in 1-min blocks before, during, and for 1 h after ischemia. Before ischemia, hypoglycemic (blood glucose less than 3 mM) diabetic rats had an increased Pi peak intensity, with no significant pH change, compared with other groups. During ischemia, the rate and extent of hydrolysis of high-energy phosphate metabolites (as measured by an increase in Pi) decreased, and the severity of tissue acidosis increased as preischemia blood glucose concentration increased. Among hyperglycemic BB rats, similar ischemia-induced changes were found for subgroups with blood glucose levels of 13.7 +/- 1.2 and 20.3 +/- 0.6 mM, in keeping with the known decrease in hexose binding sites associated with chronic hyperglycemia. Decline in PCr level during ischemia was not significantly different between groups. With reperfusion, both Pi and pH values rapidly returned to preischemia values. PCr levels, however, did not recover in hyperglycemic diabetic animals, with the degree of residual impairment dependent on the preischemia glucose level. Results suggest that optimal management of diabetes may lessen the degree of injury within the ischemic penumbra in diabetic patients who suffer a stroke.
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PMID:Forebrain ischemia in diabetic and nondiabetic BB rats studied with 31P magnetic resonance spectroscopy. 139 7

During induced myocardial ischemia for cardiac surgery, myocardial stunning occurs and aerobic metabolism of glucose, fatty acids, and lactate is inhibited as anaerobic pathways predominate. Even following reperfusion, stunned myocardium uses oxygen and substrate inefficiently leading to poor functional recovery as less mechanical work is developed per oxygen utilized. Amino acids potentially can act as cardiac metabolic substrates during and after ischemia, utilizing the transamination of amino acids by the malate-aspartate shuttle to form high energy phosphates via the tricarboxylic acid cycle. We investigated if "preloading" hearts with a physiologic spectrum of amino acids could increase postischemic myocardial recovery. Isolated perfused rabbit hearts were subjected to 120 min of 34 degrees C cardioplegic ischemia. Hearts received cardioplegia alone as controls or were "preloaded" with a 0.05% amino acid perfusion for 30 min prior to cardioplegic ischemia. Following reperfusion, analysis of functional recovery revealed that contractility and cardiac efficiency were improved with amino acids substrate preloading. The mechanism of this may be due to uptake of amino acids prior to ischemia, which are later utilized for internal reparative work during ischemia and external contractile work after ischemia.
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PMID:Amino acid substrate preloading and postischemic myocardial recovery. 140 15

A short period of global ischemia results in the death of selected subpopulations of neurons. Some advances have been made in understanding events which might contribute to the selectivity of this damage but the cellular changes which culminate in neuronal death remain poorly defined. This overview examines the metabolic state of tissue in the post-ischemic period and the relationship of changes to the development of damage in areas containing ischemia-susceptible neurons. During early recirculation there is substantial recovery of ATP, phosphocreatine and related metabolites in all brain regions. However, this recovery does not signal restitution of normal energy metabolism as reductions of the oxidative metabolism of glucose are seen in many areas and may persist for several days. Furthermore, decreases in pyruvate-supported respiration develop in mitochondria from at least one ischemia-susceptible region at times coincident with the earliest histological evidence of ischemia-induced degeneration. These mitochondrial changes could simply be an early marker of irreversible damage but the available evidence is equally consistent with these contributing to the degenerative process and offering a potential site for therapeutic intervention.
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PMID:Energy metabolism and selective neuronal vulnerability following global cerebral ischemia. 140 79


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