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

The known cytoprotective properties of MgSO4 led the authors to study its effects on infarct size in rats when administered intraarterially before reversible focal ischemia. Following an intracarotid infusion of MgSO4 in the amount of 30 mg/kg (24 animals), 90 mg/kg (18 animals), or an equal volume of vehicle (23 animals), middle cerebral artery occlusion was produced in rats by means of an intraluminal suture technique. Reperfusion occurred after 1.5 (42 animals) or 2 hours (23 animals) of ischemia. Automated, volumetric measurements of 2',3',5'-triphenyl-2H-tetrazolium chloride-stained coronal brain sections demonstrated a statistically significant decrease in infarct size for MgSO4 treatment groups compared to controls. Cytoprotection was greater in animals subjected to 1.5 hours of ischemia (28.4% reduction in infarct volume, p < 0.001, Student's t-test), than in those having 2 hours of ischemia (19.3% reduction, p < 0.05). Animals given 90 mg/kg MgSO4 prior to 1.5 hours of ischemia (12 animals) showed a 59.8% reduction in infarct volume compared to controls (11 animals, p < 0.001) and a 43.1% reduction compared to the 30 mg/kg group (11 animals, p < 0.001). Analysis of variance demonstrated the statistically significant effects of MgSO4 doses on infarct volume across all groups (F = 22.95, p < 0.0001). The neuroprotective effect of intraarterial MgSO4 in this model is robust, dose dependent, and related to the duration of ischemia. The compound may be valuable for limiting infarction if given intraarterially before induction of reversible ischemia during cerebrovascular surgery.
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PMID:Neuroprotective effects of preischemia intraarterial magnesium sulfate in reversible focal cerebral ischemia. 868 60

Several algorithms for the calculation of ionized intracellular magnesium concentration from the chemical shifts of MgATP were compared, using in vivo 31P NMR data obtained from swine brain during and following hypoxic ischemia plus i.v. MgSO4 infusion. This analysis reveals that both the absolute ionized intracellular magnesium and relative changes in magnesium may vary widely between algorithms used. The calculated intracellular pH, used in algorithms to determine ionized magnesium concentration was found to be a critical parameter that governs the extent of these differences.
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PMID:Calculation of intracellular cerebral [Mg2+] during hypoxic ischemia by in vivo 31P NMR. 905 97

Severely birth-asphyxiated human infants develop delayed ("secondary") cerebral energy failure, which carries a poor prognosis, during the first few days of life. This study tested the hypothesis that i.v. magnesium sulfate (MgSO4) after severe transient cerebral hypoxia-ischemia decreases the severity of delayed energy failure in the newborn piglet. Twelve piglets underwent temporary occlusion of the common carotid arteries and hypoxemia. Resuscitation was started when cerebral [phosphocreatine (PCr)]/[inorganic phosphate (Pi)], as determined by phosphorus magnetic resonance spectroscopy, had fallen virtually to zero, and nucleotide triphosphate (NTP) had fallen below a third of baseline. The piglets were randomized to receive, blind, either: 1) three i.v. infusions of 12.5% MgSO4 heptahydrate solution: 400 mg.kg-1 MgSO4.7H2O starting 1 h after resuscitation, and 200 mg.kg-1 12 and 24 h later (n = 6); or 2) three infusions of placebo, 0.9% NaCl (n = 6). Phosphorus and proton spectroscopy were continued until 48 h after resuscitation, and values were compared between the two groups. Mean plasma magnesium levels, 1 h after each of the three doses of MgSO4, were 2.1, 2.0, and 1.9 mmol.L-1, respectively. The severity of the primary insult, determined by the time-integral of depletion of cerebral [NTP]/[exchangeable phosphate pool (EPP)], was similar in the MgSO4-treated and placebo groups. After resuscitation, there was no difference in the progression or severity of delayed energy failure between the two groups, as judged by cerebral [PCr]/[Pi], [NTP]/[EPP], or lactate/creatine and N-acetylaspartate/creatine peak-area ratios. We conclude that MgSO4 did not decrease the severity of delayed cerebral energy failure.
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PMID:Magnesium sulfate after transient hypoxia-ischemia fails to prevent delayed cerebral energy failure in the newborn piglet. 907 50

Magnesium is a potential neuroprotective agent in the treatment of head injury and ischemia whose efficacy is likely determined by increases in brain extracellular fluid (ECF) magnesium, which in turn depends on its concentration in plasma. The objectives of this study were to: 1) examine the effects of increasing plasma magnesium concentration ([Mg]plasma) to 4-6 mM on brain ECF magnesium concentration ([Mg]ECF) and 2) determine whether maturational changes occur in the transfer of magnesium into brain ECF for newborn and more mature (approximately 1 month old) miniswine. Increases in [Mg]plasma by systemic administration of MgSO4 resulted in similar maximal elevations in brain [Mg]ECF for both age groups (193+/-76% versus 253+/-106% of control for newborn and 1-month-old miniswine, respectively). Calculations of half-lives (t1/2) for the increase and decrease in magnesium concentration (t1/2 uptake and t1/2 clearance) were used to characterize magnesium kinetics in plasma and brain ECF. Plasma magnesium uptake was shorter in 1-month-old (t1/2 = 11.1+/-0.9 min) compared with newborns (12.9+/-1.7 min, p < 0.05). The faster increase in [Mg]plasma probably contributed to a faster uptake of brain [Mg]ECF in 1-month-old compared with newborn swine (t1/2 uptake = 27.9+/-12.8 versus 46.0+/-20.9 min, respectively, p < 0.05). Although plasma magnesium clearance was shorter in 1-month-old swine compared with newborn (t1/2 = 34.3+/-7.0 versus 74.7+/-33.7 min, respectively, p < 0.05), the clearance of magnesium from the brain ECF was similar for each age group. Reductions in blood pressure and heart rate occurred during hypermagnesemia and were similar in each age group. This study shows that acute elevations in [Mg]plasma to 4-6 mM result in similar relative increases in brain [Mg]ECF for both newborn and 1-month-old miniswine. However, there are maturational differences, as demonstrated by the faster rate of magnesium uptake into the ECF observed in the older miniswine.
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PMID:Age-dependent differences in the relationship between plasma and brain extracellular fluid concentrations of magnesium after MgSO4 infusions in miniswine. 1047 42

Transient perinatal hypoxia-ischemia (HI) can lead to delayed cerebral damage beginning 8-24 h after resuscitation. Cerebroprotective therapies applied soon after HI may thus reduce the severity of brain injury. We have previously shown that MgSO4 administration to newborn piglets after HI fails to prevent the delayed global impairment in cerebral energy metabolism characteristic of severe brain damage. However, high extracellular concentrations of magnesium ions have been found to prevent specific excitotoxic neural cell death in vivo and in vitro. This study therefore examined the hypothesis that MgSO4 administration after HI reduces damage in some regions of the brain even though global energy metabolism is unaffected. Twelve newborn piglets were subjected to global cerebral HI by transient occlusion of both common carotid arteries and reduction of the inspired oxygen fraction to 0.12 until cerebral high-energy phosphates, measured by magnetic resonance spectroscopy, were significantly depleted. Subjects were randomly assigned to two groups of six: the first received MgSO4 (three doses, 400 mg/kg 1 h after resuscitation and 200 mg/kg at 12 and 24 h), and the second received placebo infusions. At 48 h after the start of the experiment, the piglets were killed and their brains were perfused, fixed, and embedded in paraffin wax. Five-micrometer sections were stained with hematoxylin and eosin to allow semiquantitative analysis of the severity and extent of injury to the hippocampus, cerebellum, cerebral cortex, caudate nucleus, thalamus, and striatum and the white matter tracts. There was no difference in the severity of tissue damage between the MgSO4-treated group and the placebo-treated animals in any brain region.
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PMID:Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn piglet does not protect against cerebral damage. 1096 May 1

The effects of magnesium sulfate (MgSO4) on sodium currents (Na(+) currents) were studied in freshly dissociated hippocampal CA(1) neurons of rat using the whole-cell patch-clamp technique. The results indicated that MgSO4 caused a concentration-dependent and voltage-dependent decrease in Na(+) currents. The half-inhibitory concentration (IC(50)) was 4.05 mmol/L. This action was frequency-independent. The results also showed that 4 mmol/L MgSO4 shifted the steady state activation curve of Na(+) currents towards positive potential (control V(h)=-55.8+/-6.8 mV, MgSO4 V(h)=-34.2+/-6.2 mV, n=8, P<0.01) without changing the slope factor. However, the steady state inactivation curve was not affected. These results suggest that blockade of Na(+) currents by MgSO4 might be an interpretation for its neuroprotection against damages induced by ischemia and oxygen deprivation.
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PMID:[Inhibition of sodium currents in acutely isolated hippocampal CA1 neurons of rats by magnesium sulfate]. 1250 30

Hydrocephalus causes damage to periventricular white matter at least in part through chronic ischemia. Magnesium sulfate (MgSO4) has been shown to be protective in various models of neurologic injury. We hypothesized that this agent would ameliorate the effects of experimental childhood-onset hydrocephalus. Hydrocephalus was induced in 3- and 4-wk-old rats by injection of kaolin into the cisterna magna. Tests of cognitive and motor function were performed on a weekly basis. In a blinded and randomized manner, MgSO4 was administered in two separate experiments (s.c. injection 0.85, 4.1, or 8.2 mM/kg/d), supplemented by osmotic minipump infusion (0.03 mM/d) to prevent low trough levels for 2 wk, beginning 2 wk after induction of hydrocephalus. The brains were then subjected to histopathological and biochemical analyses. With the 4.1 mM/kg/d dose, serum Mg++ levels were elevated transiently from 1.3 to approximately 7 mM/L. We observed statistically significant improvement in gait performance and reduced astroglial reaction. There was also a trend to improved memory performance, but no evidence of increased myelin or synaptic protein content. The 8.2 mM/kg/d dose was associated with sedation and there was no evidence of improvement in any parameter. We conclude that MgSO4 might be mildly protective in experimental hydrocephalus.
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PMID:Magnesium sulfate therapy is of mild benefit to young rats with kaolin-induced hydrocephalus. 1262 Oct 98

Cardioprotection by Mg Sulfate (MgSO4) during ischemia/reperfusion (I/R) is attributed largely to the Mg2+ cation. However, Mg-gluconate (MgGl2) may provide added benefit, possibly through its anion's antioxidant properties. Protective effects of both Mg-salts and their anions during 30 min global I and 50 min R were assessed in Langendorff-perfused (Krebs-Henseleit buffer) rat hearts. Recovery of function was compared between untreated hearts and those receiving supplement (2.4 mM MgGl2, MgSO4, or Na2SO4, or 4.8 mM NaGI) for 5 min prior to I and during the initial 30 min R. The final 20 min R was conducted without supplement. End diastolic pressure (EDP, mmHg) of the 50 min reperfused MgGl2 group (2.6) was lower than MgSO4 (16.2) and untreated (35.6) groups, and the NaGI group (25.2) was considerably lower than Na2SO4 (38.8). Recovery of developed pressure (% preischemic DP) at the onset of R for MgGl2 (74.9) was greater than MgSO4 (37.9) and untreated (33.2). After 50 min, MgGl2 (77.9) and MgSO4 (66.9) provided protection compared to untreated (51.8). In separate studies, ESR spin trapping with alpha-phenyl-N-tert-butylnitrone (3 mM PBN) showed that I/R alkoxyl radical production was reduced with MgGl2 (0.0 vs. 2.4 vs. 3.6 mM: 184 vs. 97 vs. 54.8 nM/g tissue x min) to a greater extent than seen with MgSO4 (3.6 mM: 108). Additional studies suggest that Gl(1-), unlike SO4(2-), may scavenge hydroxyl radicals, accounting for the added protection. MgGl2 treated hearts exhibited less postischemic dysfunction and oxidative injury compared to MgSO4, suggesting the contribution of Gl(1-) to cardioprotection.
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PMID:Mg-gluconate provides superior protection against postischemic dysfunction and oxidative injury compared to Mg-sulfate. 1270 53

The mechanism of neuroprotection associated with systemically administered magnesium remains unclear. This investigation examined the acute effects of systemically administered MgSO4 on brain extracellular ([Mg]ecf) and intracellular ([Mg]i) fluid Mg concentrations, specific brain phosphorylated metabolites, and brain intracellular pH. Miniswine were studied with P-31 magnetic resonance spectra, to derive [Mg]i, and brain microdialysis probes, to measure [Mg]ecf. Animals were infused with MgSO4 (n = 5, 275 mg/kg over 30 min followed by 100 mg/kg over 30 min, designated MgHI) or Na2SO4 (n = 5, designated NaHI), and both groups underwent hypoxia-ischemia (HI) over the last 15 min of the infusions. Groups differed in plasma [Mg] at the completion of HI (9.1 +/- 1.5 versus 1.1 +/- 0.6 mM for MgHI and NaHI, respectively, p < 0.05). MgHI had elevations of [Mg]ecf (0.23 +/- 0.11 and 0.40 +/- 0.14 mM at control and completion of HI, respectively), and [Mg]ecf was unchanged for NaHI (p < 0.05 versus MgHI). At the completion of HI, MgHI had greater decreases in nucleoside triphosphate (NTP) (48 +/- 6% of control), and more brain acidosis after HI (6.01 +/- 0.07) compared with NaHI (NTP, 70 +/- 3% of control; brain pH, 6.51 +/- 0.14, both p < 0.05 versus MgHI). [Mg]i increased to elevated values during HI in both MgHI and NaHI (p < 0.05 versus control of each group) and remained higher in MgHI over the next 25 min (p < 0.05 versus NaHI). There were inverse correlations during HI between [Mg]i and brain NTP (r2 = 0.73 and 0.59 for MgHI and NaHI, respectively), and brain acidosis (r2 = 0.85 and 0.85 for MgHI and NaHI, respectively) in each group. These findings indicate complex effects of Mg on the brain. Elevation of [Mg]ecf may be beneficial with regards to excitatory neurotransmitters. However, greater disturbance of brain NTP concentration, more acidosis, and the increase in [Mg]i may offset any benefit. The results warrant further investigation using indicators of neuronal injury to determine whether Mg supplementation provides neuroprotection.
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PMID:The effects of systemic magnesium sulfate infusion on brain magnesium concentrations and energy state during hypoxia-ischemia in newborn miniswine. 1456 83

Studies on the neuroprotective effect of magnesium treatment in animal models of focal and global cerebral ischemia have produced inconsistent results. Nevertheless, two magnesium acute stroke phase III trials (IMAGES and FAST-MAG) have either been completed or are planned. Therefore, we decided to re-evaluate the efficacy of magnesium following focal cerebral ischaemia in rats. Two experiments were carried out in two independent laboratories based in Australia. Both used the intraluminal thread method to induce focal cerebral ischemia in the rat. In the Perth study the middle cerebral artery (MCA) was occluded for 45 min and body temperature was controlled during and after ischemia. In the Canberra laboratory the MCA was occluded for 2 h and body temperature was only controlled during surgery. Three different doses (180, 360, or 720 micromol/kg) of MgSO4 in the Perth study and two different MgSO4 doses (370 or 740 micromol/kg) in the Canberra study were intravenously or intra-arterially administered immediately before ischemia. Control animals were given an equal volume of normal saline just before ischemia in both studies. Twenty-four or 72 h post-ischemia, infarct volume was determined following 2',3',5'-triphenyl-2H-tetrazolium chloride (TTC) staining. No significant differences (P > 0.05) in total, cortical and striatal infarct volumes between saline and MgSO4 treated animals were observed in either study. We conclude MgSO4 does not reduce infarct volume when administered before focal cerebral ischemia in rats.
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PMID:Magnesium sulfate fails to reduce infarct volume following transient focal cerebral ischemia in rats. 1519 83


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