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Effect of magnesium on restenosis after percutaneous transluminal coronary angioplasty: a clinical and angiographic evaluation in a randomized patient population. A pilot study. The Ichilov Magnesium Study Group.

Restenosis is a major clinical problem following successful percutaneous transluminal coronary angioplasty. Since magnesium has vasodilator and antithrombotic effects, this study was designed to evaluate its potential to decrease the rate of restenosis. In an open-labelled, randomized controlled study, 148 patients underwent successful coronary angioplasty. Ninety-eight patients were treated with 46-52 mmol/18-20 h intravenous magnesium sulphate (groups M1 and M2), and 49 of them continued with oral supplements of magnesium hydroxide 600 mg.day-1 (group M2). The other 50 patients served as controls (group C). Coronary angiography was performed before, immediately after and at 6 months follow-up or earlier if clinically indicated. Clinical, laboratory, ergometric and radionuclide evaluations were also carried out. One hundred and thirty-nine patients (94%) with 163 dilated segments completed the study. Intravenous magnesium was well tolerated. The cross-sectional area at the site of angioplasty increased by 3.55 +/- 2.01 mm2 in groups M1 and M2 compared with an increase of 2.90 +/- 1.63 mm2 in the control group, (P = 0.03). A trend towards a lower rate of restenosis (> 50% reduction in luminal diameter) was noticed in the magnesium groups (28/110, 25%) compared with the control group (20/53, 38%) P = 0.10. Oral administration of magnesium was well tolerated, did not have an additive effect on restenosis, but an improved clinical course was noted. It is concluded that intravenous administration of magnesium in patients undergoing coronary angioplasty is feasible and safe and that the beneficial trend of magnesium to prevent acute recoil and late (within 6 months) restenosis is encouraging and should promote further investigation in a larger patient population.

Administration, Oral↗

Effect of intravenous magnesium sulfate on cardiac arrhythmias in critically ill patients with low serum ionized magnesium.

Magnesium affects cardiac function, although until the recent development of a new ion-selective electrode no method existed for measuring the physiologically active form of magnesium, free ions (iMg2+), in the blood. We investigated the antiarrhythmic effect of magnesium sulfate administered to critically ill patients with cardiac arrhythmias and reduced iMg2+ as determined using the ion-selective electrode. Eight patients with a low iMg2+ level (less than 0.40 mmol/L) were given intravenous magnesium sulfate (group L). Magnesium sulfate was also administered to patients with a normal iMg2+ level (more than 0.40 mmol/L) but who did not respond to conventional antiarrhythmic drugs (group N). Intravenous magnesium sulfate significantly increased the iMg2+ level in patients in group L from 0.35 +/- 0.06 mmol/L (mean +/- SD) to 0.54 +/- 0.09 mmol/L (p < 0.01), and had an antiarrhythmic effect in 7 of the 8 patients (88%). However, in group N patients, intravenous magnesium sulfate had an antiarrhythmic effect in only 1 of the 6 patients (17%) (p < 0.05 vs group L). These results suggest that intravenous magnesium sulfate may be effective in the acute management of cardiac arrhythmias in patients with a low serum iMg2+ level.

Aged↗

Magnesium deficit and sudden infant death syndrome (SIDS): SIDS due to magnesium deficiency and SIDS due to various forms of magnesium depletion: possible importance of the chronopathological form.

Sudden Infant Death Syndrome (SIDS) might be due to the fetal consequences of a Mg maternal deficiency, which might be prevented by simple atoxic nutritional Mg intake by the mother. Various stresses in the pregnant women or in the infant may transform a simple Mg deficiency into Mg depletion which may not be cured by nutritional Mg supplement, but requires a correction of its causal dysregulation. Beside the well established risk factors in baby care and in the environment, it is important to stress the possible role of a primary hypofunction of the biological clock. This may be treated by darkness therapy: total light deprivation at night for the infant and atoxic nutritional Mg supplement for the pregnant women. The place in the prevention of SIDS of Mg therapy for the infant and of the use of melatonin, L-tryptophan and taurine is now uncertain yet.

Adult↗

Removal of aqueous ammonium with magnesium phosphates obtained from the ammonium-elimination of magnesium ammonium phosphate.

In order to recycle magnesium ammonium phosphate (MgNH4PO4.6H2O: MAP) obtained from MAP process, which is one of the attractive processes for removal of aqueous ammonium and phosphate from wastewater, ammonium elimination from MAP to magnesium phosphates and ammonium incorporation into the magnesium phosphates have been investigated in the present study. It is confirmed that magnesium hydrogen phosphate (MgHPO4) is favorably obtained from the ammonium elimination from MAP at temperatures greater than 353 K, although magnesium phosphate (Mg3(PO4)2) and magnesium pyrophosphate (Mg2P2O7) have been suggested as possible candidates. Based on the dissolution-precipitation mechanism for the removal of aqueous ammonium with magnesium phosphates, three magnesium phosphates were employed for the removal of aqueous ammonium. The order of the removal rate of the aqueous ammonium was MgHPO4>Mg3(PO4)2>Mg2P2O7, as expected from the solubility of those magnesium phosphates. The removability of the solid obtained from ammonium elimination of MAP is also confirmed. The present results show that MAP can be employed as an advanced material for the removal/recovery of ammonium, although it is generally accepted that an excess of MAP obtained from the wastewater treatment can be only used as a slow-acting fertilizer.

Journal Article↗

[Magnesium aspartate as a cardioprotective agent and adjuvant in tocolysis with betamimetics. Animal experiments on the kinetics and calcium antagonist action of orally administered magnesium aspartate with special reference to simultaneous vitamin B administration].

With pregnant Wistar-rats, suffering from alimentary magnesium deficiency, absorption and distributing of Mg28 has been studied, the latter having been applied as aspartate and as chloride, with and without simultaneous substitution of vitamin B6. Absorption and tissue pooling were found to be augmented when using the aspartate and even more when adding vitamin B6. These differences were significant in the blood as well as in fetal and myocardial tissue. Correlation between blood-Mg28 und Mg28-activities in various tissues shows, that blood magnesium levels indicate a magnesium deficiency at least in the tissues of interest: fetus, myocardium, uterus and placenta. Nevertheless blood magnesium levels fail to reflect an additional tissue pooling, that exerts a beneficial action in the respect of cardio protection and of saving beta-mimetic tocolytics. When measuring magnesium and calcium excretion during chronic experiments with and without oral magnesium aspartate substitution, it could be demonstrated, that the amount of substituted magnesium has been pooled almost totally. Oral magnesium substitution furthermore reduces intestinal calcium absorption. Investigation on calcium uptake into the maternal myocardium revealed, that oral magnesium aspartate substitution significantly diminishes myocardial calcium uptake, the latter among others being responsible for cardiac hazards during tocolysis with beta-mimetic substances, while the pharmacologic calcium-antagonist Verapamil failed to do so.

Animals↗

Ionized magnesium in erythrocytes--the best magnesium parameter to observe hypo- or hypermagnesemia.

BACKGROUND: Almost 99% of the body magnesium is inside cells. The concentration of intracellular ionized magnesium (iMg) is physiologically relevant. iMg in erythrocytes is a new parameter that can help to establish reliable information on the functional magnesium status. METHODS: iMg concentration in erythrocytes and serum was measured by ion-selective electrode, in clinical analyzer Microlyte (KONE). Total magnesium (tMg) concentration was measured by atomic absorption spectrometry (AAS). Albumin and total protein concentration were measured colorimetrically. RESULTS: In critically ill postoperative patients, the mean of albumin, protein and hematocrit concentration was significantly lower compared to healthy individuals. Hypomagnesemia was found in 15.9% patients as tMgs, at 22.2% as iMgs and 36.5% as iMge. Significant correlations are between iMgs and tMgs or iMge and iMgs/tMgs. In dialyzed patients, the mean of hematocrit was significantly lower, iMge was significantly higher compared with healthy individuals. Significant negative correlations are between iMgs and tMge or iMge/tMge and tMge. CONCLUSIONS: iMge is the best magnesium parameter to observe hypo- or hypermagnesemia for both groups of patients. The function of magnesium is mainly intracellular and intracellular magnesium concentrations can be the method to evaluate the magnesium status.

Adolescent↗

Intravenous magnesium sulphate relieves migraine attacks in patients with low serum ionized magnesium levels: a pilot study.

1. We tested the hypothesis that patients with an acute attack of migraine headache and low serum levels (< 0.54 mmol/l) of ionized magnesium are more likely to respond to an intravenous infusion of magnesium sulphate (MgSO4) than patients with higher serum ionized magnesium levels. 2. Serum ionized magnesium levels were drawn immediately before infusion of 1 g of MgSO4 in 40 consecutive patients with an acute migraine headache. 3. Pain reduction of 50% or more as measured on a headache intensity verbal scale of 1 to 10, occurred within 15 min of infusion in 35 patients. In 21 patients, at least this degree of improvement or complete relief persisted for 24h or more. Pain relief lasted at least 24h in 18 of 21 patients (86%) with serum ionized magnesium levels below 0.54 mmol/l, and in 3 of 19 patients (16%) with ionized magnesium levels at or above 0.54 mmol/l (P < 0.001). Mean ionized magnesium levels in patients with relief lasting for at least 24h were significantly lower than in patients with no relief or brief relief (P < 0.01). 4. Measurement of serum ionized magnesium levels may be useful in identifying patients with migraine headaches who may respond to an intravenous infusion of MgSO4.

Adult↗

Relationship between uterine contractions and serum magnesium levels in patients treated for threatened preterm labour with intravenous magnesium sulphate.

We aimed to correlate the assessment of preterm uterine activity with serum magnesium levels in women with threatened preterm labour. The observational study involved twelve women receiving intravenous magnesium sulphate for threatened preterm labour. Mean gestational age at initiation of therapy was 26.9+/-2.9 weeks. Mean cervical dilatation at initiation of therapy was 1.5 cm. Serum magnesium levels and evaluation of uterine contractions by external tocograph were assessed twice daily. Presence or absence of contractions was analysed for correlation with plasma magnesium levels. Eighty-eight measurements were analysed. The mean serum magnesium levels were 1.9+/-0.5 mmol/l and 1.9+/-0.3 mmol/l in the presence (n=22) or absence (n=66) of contractions, respectively. The difference did not reach statistical significance. No correlation was found between serum magnesium levels and presence of contractions (P=0.3, logistic regression odds ratio 1.1, 95% confidence interval of 0.6-2.0). The abolition of premature uterine contractions during intravenous magnesium sulphate therapy does not correlate with serum magnesium levels.

Adult↗

Effect of pyridoxine and magnesium on stress-induced gastric ulcers in mice selected for low or high blood magnesium levels.

Gastric ulcers were induced by immobilization in adult female mice with genetically low (MGL) or high (MGH) blood magnesium levels, obtained by selective breeding at the CSAL-CNRS (Orléans, France). All animals, fed with the same standard diet rich in magnesium, were divided into four groups of 20 animals and injected subcutaneously every 2 days for 10 days with isotonic saline (group 1), pyridoxine chlorhydrate 1.11 mg/kg in saline (group 2), magnesium lactate 149 mg/kg in saline (group 3) or both pyridoxine and magnesium (group 4). Subsequently, animals were submitted to a complete fast and an immobilization stress for 17 h. Then, they were sacrificed and the gastric mucosa was dissected for ulcer count. Among the controls (group 1), the mean number of gastric ulcers per mouse was significantly larger in the MGL than in the MGH line (p = 0.0003). In the MGH line, no significant differences were observed between control and treated groups. In the MGL line, pyridoxine associated or not with magnesium (groups 2 and 4) significantly reduced the mean number of ulcers. Magnesium treatment alone (group 3) had little effect. These results can be compared with the greater vulnerability to stress previously observed in Swiss mice fed with a magnesium-deficient diet. However, in this latter group, the number of stress ulcers was reduced not only by pyridoxine but also by the sole magnesium treatment, contrary to our present findings in MGL mice.

Animals↗

Acute cord occlusion increases blood ionized magnesium concentration in preterm fetal sheep during maternal magnesium sulfate exposure.

This study tested the hypothesis that a pathophysiologic insult to the fetus that decreases pH (umbilical cord occlusion) produces an increase in physiologically active (i.e., ionized) magnesium concentration. Preterm pregnant sheep (n = 7) were instrumented with maternal and fetal catheters and an inflatable vascular occluder was placed around the umbilical cord. After a 2-day recovery period, each ewe received a 4-g loading dose, followed by continuous intravenous infusion of 1 g magnesium sulfate/h. After 48 h, an episode of acute fetal distress was produced by inflation of the umbilical occluder for 10 min. Maternal and fetal arterial blood samples were collected at regular intervals to quantitate ionized magnesium concentration and monitor physiologic status. Magnesium sulfate infusion increased maternal and fetal blood ionized magnesium concentration. In vitro blood analysis demonstrated that there was a linear inverse correlation (r2 = 0.99) between fetal sheep blood pH and ionized magnesium concentration. In vivo, 10 min of umbilical cord occlusion produced an increase in fetal blood ionized magnesium concentration in all animals (P = 0.02) that was temporally related to the decrease in fetal blood pH. Whether this increase in physiologically active magnesium concentration is beneficial (via neuroprotection) or deleterious (via suppression of stress response) to the distressed fetus remains to be determined.

Animals↗

[Feedback of the magnesium ion on the parathyroid hormone: differences in the action of magnesium sulfate and pyrrolidone carboxylate].

Fourty-five minutes after an intravenous injection of Mg SO4 (170 mg of element Mg), in 7 young and healthy men, a significant decrease in circulating 53-84 PTH has been observed. An injection of magnesium pyrrolidone carboxylate (170 mg of Mg) failed to induce changes in plasma levels of PTH. The urinary excretion of Mg was 2-fold higher after the injection of Mg SO4 than after the injection of magnesium pyrrolidone carboxylate. For both magnesium salts used, the time patterns of plasma magnesium concentrations were the same and red blood cells magnesium was not increased. These results suggest that, in our experimental conditions, the retention of magnesium was higher after magnesium pyrrolidone carboxylate than after Mg SO4 and that the drop in plasma PTH could partly explain the larger urinary excretion of magnesium after Mg SO4.

Adult↗

Magnesium status and parenteral magnesium sulphate therapy in acute aluminum phosphide intoxication.

The results of an open randomized study on magnesium status and parenteral magnesium sulphate therapy in acute aluminium phosphide intoxication are presented. The study was conducted on 105 patients divided into two group (I & II). Patients of Group I did not receive parenteral magnesium and acted as blank. Magnesium levels were monitored every 6 h for 24 h. Patients of group II received magnesium sulphate therapy. It was administered as 1.0 g (8.1 mEq or 4.05 mmol) magnesium sulphate dissolved in 100 ml of 5 per cent dextrose intravenously as a bolus dose followed by 1.0 g every hour for three successive hours, then 1.0 g every 6 h as a maintenance dose for the next 24 h as intravenous infusion in 5 per cent dextrose. The total dose of magnesium sulphate infused was 30.0 mmol over a period of 24 h (initial dose), then 16.0 mmol (4.0 g) daily till final outcome or a maximum of five days. All the vital parameters were monitored. All the patients were followed till final outcome. The resuscitation methods used were the same in both groups. At the end of the study, mortality rates were calculated in both groups. Hypomagnesaemia was observed as the constant finding in patients of Group I. It was transient and reversed itself without MgSO4. The mortality rate was 52 per cent. On the other hand, magnesium levels rose immediately after parenteral MgSO4 administration in patients of group II and they remained persistently above normal during the observed period.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Serum & tissue magnesium content in patients of aluminium phosphide poisoning and critical evaluation of high dose magnesium sulphate therapy in reducing mortality.

Role of high dose magnesium sulphate therapy was evaluated in 50 patients of Aluminium Phosphide (AIP) poisoning. Simultaneously serum and RBC magnesium levels were studied in these patients at six different points within first 24 hours. In non-survivors magnesium content of various tissues (brain, stomach, kidneys, liver, lungs and heart) was also estimated. Magnesium estimation (tissue as well as serum) was done using atomic absorption spectrophotometer. No significant difference was found in dose related mortality rates in patients treated with and without magnesium sulphate. The immediate causes of death in these patients included intractable shock, shock coupled with arrhythmias and adult respiratory distress syndrome (ARDS). Serum as well as RBC magnesium content was within normal range at all the six points (0, 1, 3, 6, 12 and 24 hours after arrival in hospital). Tissue magnesium content of various organs (in non-survivors) was more (p < 0.01) compared to that of corresponding organs in controls (accidental deaths). No significant alterations were seen in other serum electrolytes (Na, K, Ca, PO4). The data confirmed that neither there was any evidence of hypomagnesemia in these patients nor magnesium sulphate therapy improved survival. Survival can be improved (to some extent) with continuous cardiac monitoring and use of appropriate anti-arrhythmic agents. However, imposition of stringent restrictions on the free supply of AIP and caging of tablets in plastic packs with holes and spikes may yield better results in preventing AIP poisoning rather than treating these patients.

Adolescent↗

Is magnesium content in erythrocytes suitable for evaluating cation retention after oral physiological supplementation in marginally magnesium-deficient subjects?

In this study, the effects of oral magnesium supplementation were evaluated on plasma, erythrocyte, and urinary cation levels. The study was carried out with an open, cross-over and randomized design. Healthy subjects received two sachets per day of magnesium (366 mg Mg2+/d) for two 28 d cycles, separated by a 3-week washout interval. Magnesium concentrations were measured before the supplementation and at weekly intervals during the treatment. Urinary excretion of Mg was significantly increased during supplementation, with no differences among the weeks examined. Only small increases in plasma magnesium occurred, and values returned to the prestudy levels before the end of supplementation. The increase in erythrocyte magnesium, however, was statistically significant; this trend suggests the existence of a saturable mechanisms, which prevents any possible magnesium overload during oral supplementation. We conclude that erythrocytes might be considered a suitable index for evaluating the bioavailability of magnesium salts in marginally magnesium-deficient subjects.

Administration, Oral↗

Immunoregulation by neuropeptides in magnesium deficiency: ex vivo effect of enhanced substance P production on circulating T lymphocytes from magnesium-deficient mice.

The first week of dietary magnesium deficiency in rodent models is characterized by the induction of raised levels of neuropeptides (substance P [SP] and calcitonin gene related peptide [CGRP]), followed shortly thereafter by inflammatory cytokine release. Since neuropeptides participate in neurogenic inflammation, we have proposed that the neurogenic inflammatory response plays a role in the pathology of magnesium deficiency. However, the association between the early neuropeptide release and the subsequent pathology in this model remains unclear. Peripheral blood T lymphocytes were obtained from Balb/c mice fed a magnesium-deficient diet (approximately 1.8 mmol Mg/kg), or the same diet supplemented with 20 mmol MgO/kg. These cells were incubated in medium containing 10(-10) to 10(-5) M SP, after which the cells were examined for expression of SP receptors and the supernatants were collected and examined by immunochemical techniques for the presence of T lymphocyte associated cytokines. SP stimulation induced the secretion of interleukin (IL)-2, 4, 5, 10, 12, 13 and interferon-gamma (IFN-gamma). T lymphocytes from magnesium-deficient animals, when compared to magnesium-sufficient ones, secreted increased levels of these cytokines. The secretion of these cytokines was maximal at either 5 days (IL-4, IL-5) or 7 days (II-2, IL-10, and IFN-gamma) of magnesium deficiency. This increased sensitivity to SP appears to be related to an increased expression of SP receptors on the surface of T lymphocytes during the first week of magnesium deficiency. These data indicate that SP released early during magnesium deficiency exerts a regulatory role on T lymphocyte cytokine production, especially those cytokines regulating mast cell and immune responses leading to the onset of an immunopathological state.

Animal Feed↗

Intravenous magnesium sulphate in suspected acute myocardial infarction: results of the second Leicester Intravenous Magnesium Intervention Trial (LIMIT-2)

The cardiovascular actions of the magnesium ion at pharmacological concentrations include coronary and systemic vasodilatation, platelet inhibition, and antiarrhythmic effects. Magnesium has also been reported to protect myocardial tissue in experimental models of ischaemia and reperfusion. Several small clinical trials in suspected acute myocardial infarction have suggested that early mortality can be reduced by intravenous infusion of magnesium salts in the acute phase, but none has been of sufficient size to be conclusive. We therefore conducted a randomised, double blind, placebo controlled study in 2316 patients with suspected acute myocardial infarction who received either intravenous magnesium sulphate (8 mmol over 5 min followed by 65 mmol over 24 h) or physiological saline. The primary outcome measure was 28-day mortality, which was ascertained in 99.3% of patients. The groups were well balanced for prognostic factors. By intention-to-treat analysis mortality from all causes was 7.8% in the magnesium group and 10.3% in the placebo group (2p = 0.04), a relative reduction of 24% (95% confidence interval 1-43%). Within the coronary care unit the incidence of left ventricular failure was reduced by 25% (7-39%) in the magnesium group (2p = 0.009). There was no significant difference between the groups in the incidence of heart block or the use of antiarrhythmic drugs, direct-current cardioversion, or temporary pacing. Myocardial infarction was confirmed in 65% of each group, with closely similar rises in cardiac enzymes. The side-effects of magnesium treatment were transient flushing, related to speed of injection of the loading dose, and an increased incidence of sinus bradycardia (2p = 0.02). Exploratory subgroup analyses of 28-day mortality did not indicate any effect modification by thrombolysis or aspirin, or by previous treatment with beta blockers, calcium antagonists, or diuretics. Intravenous magnesium sulphate is a simple, safe, and widely applicable treatment. Its efficacy in reducing early mortality of myocardial infarction is comparable to, but independent of, that of thrombolytic or antiplatelet therapy.

Aged↗

Intravenous magnesium sulfate administration reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia: part I: comparing propofol requirements according to hemodynamic responses: part II: comparing bispectral index in control and magnesium groups.

BACKGROUND: The authors investigated whether an intravenous administration of magnesium sulfate reduces propofol infusion requirements during maintenance of propofol-N2O anesthesia. METHODS: Part I study: 54 patients undergoing total abdominal hysterectomy were randomly divided into two groups (n = 27 per group). The patients in the control group received 0.9% sodium chloride solution, whereas the patients in the magnesium group received magnesium (50 mg/kg as a bolus, then 8 mg x kg(-1) x h(-1)). To maintain mean arterial blood pressure (MAP) and heart rate (HR) at baseline value, the propofol infusion rate was changed when the MAP or the HR changed. The amount of propofol infused excluding the bolus dosage was divided by patient's body weight and total infusion time. Part II study: Another 20 patients were randomly divided into two groups (n = 10 per group). When the MAP and HR had been maintained at baseline value and the propofol infusion rate had been maintained at 80 microg x kg(-1) x min(-1) (magnesium group) and 160 microg x kg(-1) x min(-1) (control group), bispectral index (BIS) values were measured. RESULTS: Part I: The mean propofol infusion rate in the magnesium group (81.81 +/- 13.09 microg x kg(-1) x min(-1)) was significantly less than in the control group (167.57 +/- 47.27). Part II: BIS values in the control group (40.70 +/- 3.89) were significantly less than those in the magnesium group (57.80 +/- 7.32). CONCLUSION: Intravenous administration of magnesium sulfate reduces propofol infusion requirements. These results suggest that magnesium administration may have an effect on anesthesia or analgesia and may be a useful adjunct to propofol anesthesia.

Adult↗