Infusion Of Mg Research Articles

Magnesium Therapy Improves Rotational Thromboelastometry Findings Prior to Liver Transplantation: A Randomized Clinical Trial.

An important challenge during orthotopic liver transplantation (OLT) is optimal coagulation management. There are diverse studies regarding effect of Mg sulfate on coagulation system. This study evaluates the impact of Mg sulfate on the coagulation parameters of the rotational thromboelastometry (ROTEM) in patients about to undergo OLT. In this randomized clinical trial, 60 patients who were going to undergo OLT were randomly allocated into two groups. In the Mg group, the patients received a 1.5g infusion of Mg 5min before the surgical incision. In the control group, patients received a physiological saline instead of Mg. Plasma Mg levels before and after the infusions were measured in both groups. Also, three ROTEM tests: EXTEM, INTEM and FIBTEM were performed before and after the infusions. Baseline mean plasma magnesium levels were within normal range in the control and Mg groups: 2.06 and 2.18mg/dl, respectively. After magnesium therapy, the mean plasma Mg level in the Mg group increased to 2.78mg/dl in compared to the control group that was 2.01mg/dl (P < 0.000). Mean value of the clotting time (CT) in the magnesium group were significantly decreased from 129.50 ± 7.76, 381.86 ± 8.51 and 114.26 ± 6.80 to 86.13 ± 3.4, 209.33 ± 6.68 and 81.56 ± 5.01 in the EXTEM, INTEM, and FIBTEM respectively after intervention in the Mg group (P = 0.001). Among patients with end-stage liver diseases who have ROTEM evidence of hypocoagulability, magnesium could correct CT parameter of the ROTEM tests.

Efficacy of Intravenous Magnesium in Facilitating Cardioversion of Atrial Fibrillation.

Low serum magnesium (Mg) levels are associated with an increased risk of atrial fibrillation. Some studies have shown a benefit of Mg in facilitating pharmacological cardioversion. The role of an intravenous infusion of Mg alone in facilitating electric cardioversion is not clear. In a prospective, randomized, double-blind, placebo-controlled trial, we enrolled patients with atrial fibrillation who were scheduled for electric cardioversion. Patients were randomized to receive Mg or placebo before cardioversion using a step-up protocol with 75, 100, 150, and 200 J biphasic shocks. Patients with hypokalemia, hypermagnesemia, or postcardiac surgery atrial fibrillation were excluded. Patients on antiarrhythmic drugs were included as long as they were at steady state. All patients were monitored for 1 hour post procedure for the maintenance of sinus rhythm. A total of 261 patients (69% male, mean age 65.5±11.1 years) were randomized (132 and 129 patients receiving Mg and placebo, respectively). Baseline characteristics were similar between both the groups. There was no statistically significant difference in the success rate of cardioversion between the 2 groups (86.4% versus 86.0%; P=0.94), cumulative amount of energy required for successful cardioversion (123.3±55.5 versus 129.5±52.6 J; P=0.40), or the number of shocks required to convert to sinus rhythm (2.25±1.24 versus 2.41±1.22, P=0.31). No adverse events were noted in either group. In patients undergoing electric cardioversion for persistent atrial fibrillation, Mg infusion does not increase the rate of successful cardioversion. URL: https://clinicaltrials.gov. Unique identifier: NCT01597557.

The role of magnesium in cardiac arrhythmias

Magnesium plays an essential role in many fundamental biological reactions, as it is involved in more than 300 metabolic reactions. Deficiency of magnesium may result in many disorders, including cardiac arrhythmias. As intravenous magnesium has a high therapeutic to toxic ratio and a minimal negative inotropic effect, it has long been used in treatment and prevention of cardiac arrhythmias. Several studies have shown the beneficial effect of intravenous infusion of Mg during an attack of supraventricular tachycardia, indicating that the effectiveness of magnesium depends on the type of tachycardia. Magnesium has also an advantageous effect in the case of atrial fibrillation, considered a criterion of the effectiveness of atrial fibrillation acute treatment at the ventricular rate ≤ 100 min–1. As intravenous magnesium seems to be useful in prevention and treatment of various cardiac arrhythmias, it is a common component of a complex antiarrhythmic therapy.

Infusion of Mg in humans acutely reduces serum insulin levels: a pilot study

Infusion of Mg for therapeutic purposes is still a matter for debate. Dosages vary considerably, yet subclinical effects on normal physiology are largely ignored. In human and animal models, interactions between Mg and insulin exist, thus we have investigated the effect of infusing Mg on serum insulin, ionised Mg (Mg(2+)) and Ca (Ca(2+)) and plasma glucose in human volunteers. Six male volunteers were infused with magnesium sulphate (MgSO(4)) dissolved in normal saline, using a high-dose "loading" bolus, followed by a lower-level "maintenance" period. Serum Mg(2+) rose rapidly throughout the bolus infusion, declined during the maintenance phase, but remained higher than pre-infusion levels throughout the experimental period; serum Ca(2+) rose when serum Mg(2+) was highest. Infusion of MgSO(4) had no effect on heart rate or blood pressure, but caused a rapid, pronounced drop in circulating fasting insulin (p<0.0005), which slowly recovered to basal values during the course of the maintenance infusion. A slight, transient rise in plasma glucose (p<0.05) concomitant with the decline in serum insulin was also observed. It is possible that the effect of Mg(2+) on insulin may have been due to antagonism of Ca(2+) entry in pancreatic beta-cells, the insulin decline causing a subsequent rise in circulating glucose levels. We suggest that these effects of MgSO(4) infusions should be considered where the aim is to achieve high doses of blood Mg(2+) levels by clinical intervention.

Effects of Intravenous Magnesium in a Prolonged QT Interval Model of Polymorphic Ventricular Tachycardia Focus on Transmural Ventricular Repolarization

This study was performed to clarify the antiarrhythmic effects of magnesium sulfate (Mg(++)) in a prolonged QT interval canine model of polymorphic ventricular tachyarrhythmia (VTA). In six experiments in a canine model of prolonged QT by anthopleurin-A, Mg(++) was administered in boluses of 0.2 mL/kg during repetitive episodes of self-terminating polymorphic VTA or frequent premature ventricular complexes (PVCs). The distribution of ventricular repolarization across the left ventricular(LV) wall and dispersion of transmural repolarization were analyzed before, and 30 and 120 seconds after Mg(++) administration, during ventricular pacing at 100 bpm. Transmural unipolar electrograms were recorded from multipolar needle electrodes, and local activation-recovery intervals (ARI) were measured. Mg(++) rapidly eliminated self-terminating polymorphic VTA and all isolated PVCs. During ventricular pacing at 100 bpm, Mg(++) caused modest shortening of ARI at all recording sites. Since the magnitude of ARI shortening was greater at mid-myocardial sites than at other ventricular sites, mean transmural ARI dispersion decreased from 80 +/- 22 to 45 +/- 18 ms within 30 seconds after Mg(++) injection. However, this effect was transient, and, at 120 seconds after Mg(++) administration, ARI had increased all sites and transmural ARI dispersion lengthened to 65 +/- 18 ms. Besides suppression of triggered premature activity, homogenization of transmural ventricular repolarization was associated with the antiarrhythmic effects of intravenous Mg(++) in this model. Since these effects were transient, a continuous intravenous infusion of Mg(++) is preferred to prevent recurrences of VTA.

Magnesium and experimental vasospasm.

Interest has developed in the use of magnesium (Mg++) as a neuroprotectant and antivasospastic agent. Magnesium may increase cerebral blood flow (CBF) and reduce the contraction of cerebral arteries caused by various stimuli. In this study the authors tested the hypothesis that a continuous intravenous infusion of Mg++ reduces cerebral vasospasm after experimental subarachnoid hemorrhage (SAH). A dose-finding study was conducted in five monkeys (Macaca fascicularis) to determine what doses of intravenous MgSO4 elevate the cerebrospinal fluid (CSF) concentrations of Mg++ to vasoactive levels and to determine what effects these doses have on the diameters of cerebral arteries, as shown angiographically. After a standard dose of MgSO4 had been selected it was then administered in a randomized, controlled, blinded study to 10 monkeys (five animals/group) with SAH, beginning on Day 0 and continuing for 7 days, at which time angiography was repeated. A 0.086-g/kg bolus of MgSO4 followed by an infusion of 0.028 g/kg/day MgSO4 significantly elevated serum and CSF levels of Mg++ (five monkeys). Magnesium sulfate significantly elevated the serum level of total Mg++ from a control value of 0.83 +/- 0.04 mmol/L to 2.42 +/- 1.01 mmol/L on Day 7 and raised the CSF level from 1.3 +/- 0.04 mmol/L to 1.76 +/- 0.14 mmol/L. There was no angiographic evidence of any effect of MgSO4 on normal cerebral arteries. After SAH, the vasospasm in the middle cerebral artery was not significantly reduced (46 +/- 8% in the MgSO4-treated group compared with 35 +/- 6% in the placebo [vehicle]-treated group, p > 0.05, unpaired t-test). Magnesium sulfate did not significantly reduce cerebral vasospasm after SAH in the doses tested. An investigation of SAH is warranted mainly to test whether a benefit can be achieved by neuroprotection or by augmentation of CBF by dilation of small vessels and/or collateral pathways.

Intravenous magnesium reduces the rate of glucose disposal in lactating sheep.

Magnesium deficiency is generally associated with an impaired ability to dispose of glucose. In order to test whether or not increasing the peripheral free Mg concentration ([Mg(2+)]) would enhance glucose disposal, we have carried out glucose infusions in sheep with and without simultaneous infusion of Mg. Basal plasma glucose levels were higher in lactating sheep ('lactators') than in non-lactating sheep (controls) (P < 0.05). The glucose disposal rate (K(G)) with no added Mg was greater in lactators than controls (P < 0.05). When Mg was added to the infusate, K(G) in lactators was reduced (P < 0.005). Infusion of Mg depressed basal insulin levels in controls and lactators (P < 0.0001 for both). The insulin response to the intravenous glucose tolerance test (IVGTT) was lower in lactators compared with controls (P < 0.0001); however, after correcting for the reduced basal insulin level when Mg was included during the IVGTT, there was no difference between the two groups. We conclude that intravenous Mg at the doses used in this study leads to a decrease in basal insulin secretion, and that increasing serum [Mg(2+)] reduces glucose disposal in lactating sheep.

Studies on the Pathogenesis of Hypokalemia in Gitelman’s Syndrome: Role of Bicarbonaturia and Hypomagnesemia

Objective: Hypokalemia and renal potassium (K) wasting are hallmarks of the group of disorders called Bartter’s syndrome. The presence of hypomagnesemia and a low rate of excretion of calcium are currently used to characterize a subgroup of these patients as having Gitelman’s syndrome (GS) in which the molecular lesion is a defect in the thiazide-sensitive NaCl cotransporter in the distal convoluted tubule. This study was undertaken to examine whether bicarbonaturia or hypomagnesemia exacerbates the kaliuresis in patients with GS. Methods: Six patients with most of the diagnostic features of GS were examined. To examine the role of bicarbonaturia, the transtubular K concentration gradient (TTKG) was assessed before and after an oral load of NH₄Cl which caused the urine pH to be <6. To evaluate the role of hypomagnesemia, the TTKG was examined after an infusion of enough magnesium (Mg) to achieve normal levels of Mg in plasma for close to 24 h. Results: The TTKG remained very high even when the pH of the urine was <6.0. An infusion of Mg caused the TTKG to approach expected values for hypokalemia in 4 of 6 patients. The infusion of Mg was extended in 1 patient who had a sustained high TTKG for 24 h; the TTKG remained elevated for 96 h despite normal plasma Mg levels. Conclusions: Bicarbonaturia does not play a critical role in maintaining the very high TTKG in these patients. The K wasting in 4 of 6 of these patients could largely be attributed to hypomagnesemia and/or Mg depletion. The plasma aldosterone level tended to be higher in patients who did not respond to the infusion of Mg. Therefore, these patients may not represent a homogeneous group with regard to the pathophysiology of their renal K wasting.

Fructooligosaccharides stimulate the absorption of magnesium from the hindgut in rats

We investigated the effects of feeding fructooligosaccharides (FO) on the absorption of Mg from the hindgut in cecal-cannulated rats in vivo. Male rats, four wks old male rats, were divided into four groups. Rats in two groups were fed Mg-containing diet and other two groups were fed Mg-free diet with cecal infusion of Mg. Rats of both groups were fed FO-free or FO-containing diet, respectively. The absorptive ratio of Mg administrated into the cecum was similar to that of Mg fed orally in rats fed FO-free and FO-containing diet, respectively. FO-feeding significantly increased the apparent absorption of Mg in both rats fed Mg orally and rats with Mg infused into the cecum. Moreover, the extent of the increase in the absorption of Mg by infusion into the cecum and by oral feeding was the same. In a separate experiment, we observed that only the rats fed Mg-free diet exhibited auricular and facial peripheral hyperemia and hemorrhage. However such symptoms were not observed in the rats with Mg infused into the cecum. In conclusion, these results indicate that FO-feeding stimulates absorption of Mg in the hindgut mainly.

Magnesium Inhibits Platelet Activity - an Infusion Study in Healthy Volunteers

Magnesium (Mg) has shown the ability to inhibit arterial thrombus formation in some experimental animal studies. This effect may be due to an inhibition of platelet reactivity as in vitro studies have demonstrated that Mg inhibits platelet aggregation. In order to evaluate the in vivo effect of Mg in humans measurements of platelet activity, fibrinolytic activity, as well as measurements of prostacyclin (PGI2), and nitric oxide (NO) release were performed after infusion of magnesium sulphate (MgSO4) in healthy volunteers. In a placebo controlled, cross-over study in 14 healthy male subjects, 8 mmol MgSO4 was given as an intravenous bolus over 15 min followed by 3 mmol MgSO4/h. The mean S-Mg concentration increased from 0.85 to 1.50 mM during the Mg infusion period. A transient decrease in blood pressure was observed during the initial bolus infusion of Mg. Haemodynamic parameters were otherwise unstable. The bleeding time increased by 48% during the Mg infusion (p < 0.005), and in accordance with this, ex vivo platelet aggregation in platelet rich plasma was significantly inhibited, both following collagen (p = 0.02) and ADP (p = 0.04) stimulation. There were no significant changes in plasma beta-thromboglobulin concentration or the excretion of 2,3-dinor-thromboxane B2 in the urine. Neither tissue plasminogen activator (t-PA)activity, tissue plasminogen activator (t-PA)antigen nor plasminogen activator inhibitor (PAI)antigen changed during the Mg infusion period. There was no sign of increased release of PGI2 from the vessel wall as judged by urinary concentration of 2,3-dinor-6-keto-prostaglandin F1 alpha. Nor was there any sustained increase in the release of NO, measured as nitrate concentration in urine. However, a transient increase in NO release was observed during one sample period. In conclusion a reduced platelet activity and increased bleeding time, was found during Mg infusion in healthy volunteers. Fibrinolytic activity showed no changes. An anti-platelet effect may in part be responsible for the beneficial effect of Mg, described in patients with acute myocardial infarction (MI) and preeclampsia.

The site of magnesium absorption from the ruminant stomach

1. A low-magnesium diet was fed to four sheep, each of which had been surgically prepared with a rumen fistula, a tube into the cranial one-third of the omasum, a tube to the cranial one-third of the abomasum and a re-entrant duodenal cannula. Mg, as gluconate or acate or acetate, was continuously infused for 12-14 d in turn into (1) the caudal duodenal cannula, (2) the abomasum, (3) the omasum, (4) the rumen. A continuous infusion of the chromium-ethylenediaminetetraacetic acid complex (CrEDTA) was maintained to the rumen. The abomasal effluent which flowed through the cranial duodenal cannula was continually sampled and the flow of Mg calculated from the concentrations of Mg and CrEDTA. Blood and rumen fluid samples were taken and urine and faeces collected during each period of Mg infusion. 2. The Mg infused to either the abomasum or omasum was completely recovered at the duodenum, indicating a lack of net absorption of Mg from these stomach compartments. In contrast, 13-7-18-7 mmol (36-61%) of the Mg infused to the rumen was not recovered at the duodenum which suggested that a substantial net absorption of the infused Mg occurred from the reticulo-rumen. Absorption of Mg caudal to the pylorus was not related to the site of Mg infusion and averaged 3-28 +/- 0-56 (SEM) mmol/d. 3. Compared with the intraruminal infusion, the post-ruminal infusion of Mg was associated with decreased plasma and rumen fluid Mg concentrations, decreased urinary Mg exretion, decreased Mg balance and increased faecal Mg excretion. 4. It is concluded that no significant absorption of Mg occurs from either the omasum or abomasum in sheep and that the reticulo-rumen is the principal site of Mg absorption before the pylorus. Absorption of Mg post-ruminally is insufficient to maintain normal Mg status in the animal.

Continuous infusion indicator dilution measurement of limb blood flow and vascular response to magnesium sulfate in normotensive and hypotensive men.

A constant infusion, indicator dilution technique for blood flow measurements in the forearm and hand of man was tested and validated in vitro and in vivo. This technique employs jet injection to improve mixing of indicator with arterial blood. The mixing characteristics of the jet injection system were studied in vitro in tubing simulating the brachial artery of man. In addition, actual blood flows in the isolated pump-perfused forelimbs of five dogs were compared with constant infusion, indicator dilution calculated flows. Measurements were also made of mixing and of blood flow in the forearm and hand of man. The technique was used to compare forearm and hand vascular responses with constant intrabrachial arterial infusions of magnesium sulfate in 13 normotensive and 13 essential hypertensive men. In vitro and in vivo the jet injection system significantly improved mixing of indicator with blood, as compared with mixing produced by standard infusion techniques, without causing hemolysis. In 30 measurements in isolated, perfused dog forelimbs the correlation coefficient between actual and calculated blood flow was 0.992. Resting limb vascular resistance in the hypertensive group was significantly higher than in the normotensive group. Limb vascular resistance in all 26 men decreased in response to intrabrachial-arterial infusion of 0.25% magnesium sulfate (8 ml/min). Rate of infusion of Mg(++) was 0.162 mEq/min. There was a significant positive linear correlation between level of initial limb vascular resistance and magnitude of response to magnesium sulfate. Vascular response data adjusted for this source of variation were similar in hypertensives and normotensives.The data suggest that this constant infusion, indicator dilution technique allows accurate calculation of total limb blood flow in man, provided that anomalous bifurcation of the brachial artery is not present. The data also suggest that the jet injection system improves mixing of substances with arterial blood. Thus, use of this system should especially aid reliability of studies of limb vascular responses to vasoactive agents infused into the brachial artery.