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

The NMDA receptor is intimately involved an a wide range of pathophysiological processes in the mammalian brain, including epilepsy and ischemia-induced neurodegeneration. The widespread distribution of NMDA receptors places almost every area of the brain at risk from NMDA receptor over-activity. However, it is clear that the central nervous system can function effectively without imminent danger of self-destruction. The focus of this review is the processes that control NMDA receptor responsiveness in vivo. The review will cover the modulation of the receptor by Mg2+, glycine, Zn2+ and polyamines that is believed to occur by virtue of interaction with distinct ligand binding sites on the NMDA receptor complex. Studies suggesting a role for receptor phosphorylation and for redox modulation will be discussed. Finally, some evidence for indirect regulation of cellular responses to NMDA receptor activation by other neurotransmitters will be presented.
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PMID:Modulation of NMDA receptor responsiveness by neurotransmitters, drugs and chemical modification. 197 53

The effect of high concentration of magnesium on both mechanical dysfunction and metabolic damage after ischaemia-reperfusion was studied in isolated rat hearts. The heart was perfused by the Langendorff's technique at a constant flow (10 ml/min) with modified Krebs-Henseleit solution and driven at 300 beats/min. The heart was made ischaemic by reducing the flow to 0 ml/min for 25 min, and then reperfused at the constant flow for 15 min. MgSO4 was added to the perfusate for 5 min before the onset of ischaemia, or after the end of ischaemia (after the onset of reperfusion). Ischaemia-reperfusion produced both mechanical dysfunction (as evidenced by an increase in the left ventricular end diastolic pressure and a decrease in the left ventricular developed pressure) and metabolic damage [as evidenced by a decrease in the myocardial adenosine triphosphate (ATP)]. When 15 mmol/l MgSO4 was given before ischaemia, there was no appreciable recovery of mechanical function, whereas when given after ischaemia (during reperfusion), there was a marked recovery of mechanical function. Lower concentrations (10 or 5 mmol/l) of MgSO4 given after ischaemia recovered the mechanical function concentration-dependently. The beneficial effect of 15 mmol/l MgSO4 was minimized by the coexistence of 4.5 mmol/l CaCl2 in the reperfusion solution. The decrease in the myocardial level of ATP induced by ischaemia-reperfusion was attenuated by 15 mmol/l MgSO4 given in the reperfusion solution. These results suggest that high Mg2+ is effective in attenuating both functional and metabolic damage of the post-ischaemic heart, provided it is given after ischaemia.
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PMID:Beneficial effect of magnesium on the isolated perfused rat heart during reperfusion after ischaemia: comparison between pre-ischaemic and post-ischaemic administration of magnesium. 240 98

Amino acids are known to increase glomerular filtration rate (GFR). There is also an early resumption of filtration following 2-h renal ischemic stress under protection by histidine-buffered histidine-tryptophan-ketoglutarate solution (HTK), possibly due in part to an amino acid effect. Hence, we have examined the possibility of further enhancing the postischemic GFR by adding 32 (ASP I; 4 mM Mg2+) or 36 (ASP II; 6 mM Mg2+) mM L-aspartate (asp) or 32 mM DL-aspartate (ASP III) to the HTK solution in place of chloride. After infusion of 500 ml 5% glucose, canine kidneys were protected by an 8-min perfusion with HTK (n = 5), ASP I (n = 4), ASP II (n = 5) or ASP III-solution (n = 3). The subsequent ischemia lasted for 2 h at 27-31 degrees C. During reperfusion, both GFR and filtration fraction (FF) were higher in kidneys protected by L-aspartate-containing solutions. ASP III showed no improvement against HTK. An additional preischemic intra-aortal application of HTK or ASP I solution just above the exit of the renal arteries prior to the intrinsic protective perfusion further raised the postischemic GFR. The present results suggest that L-aspartate but also histidine may have favorable amino acid effects in renal protective solutions in addition to known positive effects of histidine.
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PMID:Contribution of amino acids in protective solutions to postischemic functional recovery of canine kidneys. 251 51

White mice, 18-20 g, were fed purified diets containing two weight percent safflower oil plus ten weight percent menhaden, corn, or olive oil for 2 wk. Menhaden oil ingestion resulted in significantly higher levels of 22:6(n-3) and 20:5(n-3), particularly 22:6(n-3), and lower levels of 20:4(n-6) and 18:2(n-6) in cardiac sarcoplasmic reticulum (SR) phospholipids than did corn or olive oil ingestion. These changes in fatty acid composition resulted in a significant decrease in the value of the n-6/n-3 fatty acid ratio of cardiac SR phospholipids. The ratio was 2.8 versus 0.2 in choline phospholipids and 1.9 versus 0.2 in ethanolamine phospholipids in SR of mice fed corn or menhaden oil, respectively. This reduction in the n-6/n-3 fatty acid ratio was associated with a lower relative activity of Ca2+-Mg2+ ATPase, and a lower initial rate of calcium transport and maximum calcium uptake in SR vesicles from mice fed menhaden oil rather than olive or corn oils. The specific activity of NADPH cytochrome C reductase (EC 1.6.2.3) of cardiac SR was not affected by dietary lipids. These data indicate that modification of SR by 22:6(n-3) may change the SR bilayer structure resulting in alteration of the calcium transport properties of SR vesicles. In addition, our results suggest that reduction of calcium flux across cardiac SR following fish oil consumption may also reduce the susceptibility of myocytes to rapid changes in calcium concentrations which may occur during ischemia and reperfusion.
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PMID:Ca2+-Mg2+ ATPase of mouse cardiac sarcoplasmic reticulum is affected by membrane n-6 and n-3 polyunsaturated fatty acid content. 252 49

It is established that at the early stage of total heart ischemia in rats (5-10 min) the oligomycin-sensitive ATPase activity of mitochondria measured in heart homogenates in the medium and containing no Mg2+ decreases considerably, whereas the activity of respiratory chain, the value of respiratory control and Mg2+-ATPase activity are practically unchanged. The hypothetic trigger mechanism is suggested for Mg2+ ejection from mitochondria under conditions of respiration cessation. It is supposed to be a defence reaction of cells aimed to prevent ATP hydrolysis by mitochondria under ischemia.
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PMID:[Mg2+ release from heart mitochondria in ischemia: is it the defense mechanism or damage?]. 252 29

After 10-60 min of normothermic complete ischemia, hippocampal slices were prepared and allowed to recover for 60 min. The presence or absence of an evoked transsynaptic response was measured in CA1, CA3, and dentate gyrus. A selective vulnerability of the field excitatory postsynaptic potential to ischemia was found (CA1 greater than CA3 greater than dentate gyrus). Recovery of synaptic transmission in CA1 and CA3 was significantly improved by decreasing extracellular Ca2+ and increasing Mg2+ after ischemia. Addition of an N-methyl-D-aspartate antagonist further improved functional recovery. Postischemic reduction in extracellular Cl- increased recovery in CA1 and CA3, whilst reduction in Na+ was deleterious.
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PMID:Selective vulnerability of synaptic transmission in hippocampus to ex-vivo ischemia: effects of extracellular ionic substitution in the postischemic period. 254 84

Magnesium (Mg2+) is an important regulator of cell energy metabolism, since only MgATP can serve as a substrate for ATP utilizing processes. We used 31P NMR spectroscopy to determine the complexation of ATP with Mg2+ and intracellular free Mg2+ (Mgf) in isolated rat hearts during control perfusion, ischemia and reperfusion. Atomic absorption spectrophotometry was used to determine preischemic and postischemic tissue Mg2+ and release of Mg2+ into the coronary effluent during reperfusion. Mgf increased from 0.60 mmol/l during control perfusion to greater than 6.5 mmol/l after 15 min of ischemia, while we estimated that at that time 6.7 mmol/l Mg2+ had been liberated from ATP. Less than 2% of cellular Mg2+ was released to the effluent during reperfusion after 30 min of ischemia. From spectra obtained during reperfusion the fraction of ATP that was bound to Mg2+ was calculated to be approximately 96% (compared to 94% during control perfusion), indicating that intracellular Mg2+ did not limit the metabolic use of the newly produced ATP. Mgf remained elevated during reperfusion (0.85 mmol/l). We conclude that intracellular Mg2+ deficiency due to leakage of Mg2+ to the extracellular space does not play a role in the poor postischemic recovery in this isolated rat heart model. Nevertheless, high Mg2+ prior to ischemia or during reperfusion may well be protective, due to interactions of Mg2+ with the sarcolemma or intracellular sites, affecting Ca2+,K+ and Na+ distribution and fluxes.
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PMID:Intracellular magnesium during myocardial ischemia and reperfusion: possible consequences for postischemic recovery. 260 49

Both Mg2+ and Ca2+ have been implicated as having roles in the pathomechanisms of cerebral ischemia. To further study the effects of these ions on postischemic histologic outcome, fasted rats were given one of three intravenous infusions: 5.0 mmol/kg MgCl2, 5.0 mmol/kg MgCl2 + 0.035 units/kg regular insulin, or 1.0 mmol/kg CaCl2. This resulted in elevated plasma Mg2+ or Ca2+ concentrations in the corresponding groups. A fourth group received 0.9% NaCl (saline). Preinfusion plasma glucose concentration was similar for all groups and was unchanged after infusion in rats receiving either saline or MgCl2 + insulin. In contrast, postinfusion glucose concentration was increased in the MgCl2 group (p less than 0.001) and decreased in the CaCl2 group (p less than 0.001) relative to saline-treated rats. Following respective infusions, all rats underwent 10 minutes of reversible forebrain ischemia (bilateral carotid artery occlusion and systemic hypotension) followed by 7 days' recovery. Six of 12 CaCl2-treated rats died 2-3 days after ischemia; all other rats remained neurologically indistinguishable, without gross neurologic deficits. Histologic injury in the neocortex and caudate was moderate in all groups. In the hippocampus, MgCl2 + insulin resulted in 66 +/- 6% (mean +/- SD) dead CA1 pyramidal cells, which was similar to the amount in saline-treated rats (68 +/- 10%). Injury was increased in the MgCl2 group (79 +/- 4% dead cells), while in surviving CaCl2-treated rats, injury was decreased (54 +/- 13%). We conclude that the increased injury in MgCl2-treated rats and the decreased injury noted in surviving rats receiving CaCl2 are due to the plasma glucose concentrations present prior to ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of elevated plasma magnesium versus calcium on cerebral ischemic injury in rats. 264 53

Recent evidence supports the concept that cerebral vasospasm is involved in the pathogenesis of eclampsia. Magnesium, which has a beneficial effect in eclampsia, may act by opposing calcium-dependent arterial constriction, thereby relieving vasospasm. Magnesium may also antagonize the increase in intracellular calcium concentration caused by ischemia and thus prevent cell damage and death. Magnesium might have a role in the treatment of cerebral vasospasm and ischemia, such as occurs in subarachnoid hemorrhage, ischemic stroke, and brain trauma.
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PMID:Action of magnesium sulfate in the treatment of preeclampsia-eclampsia. 267 28

Recent developments in three categories of shock research are discussed. Organ perfusion and humoral pathophysiological responses were investigated first, since the cause of fatal shock is always ischemia, tissue hypoxia and resulting cell damage with abolishment of mitochrondrial function. Both centrally and peripherally administered thyrotropin-releasing hormone (TRH) had vasopressor effects that are mediated by a central cholinergic mechanism. A derivative of TRH, DN-1417, had a longer-acting vasopressor action. TRH content increased in the brain in reversible shock, while amino acids increased in irreversible shock.
Magnesium 1989
PMID:Pathophysiology of circulatory shock: an overview. 268 42


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