Brian A. Mason

Serum ionized magnesium levels in normal and preeclamptic gestation

Objective To compare serum levels of ionized and total magnesium with those of ionized calcium, total calcium, sodium, and potassium over the course of pregnancy in normal women and in women who develop preeclampsia. Methods We collected venous serum samples from 31 pregnant women during their first, second, and third trimesters. Gestational ages ranged from 6 to 37 weeks. Samples were analyzed for ionized and total magnesium, ionized and total calcium, sodium, and potassium using a biomedical chemistry analyzer. Data were analyzed with repeated-measures analysis of variance and two-way repeated-measures analysis of variance. Results In 22 normal pregnant women, both serum ionized and total magnesium levels decreased significantly with increasing gestational age. No changes in sodium, potassium, or ionized or total calcium were observed. Nine of the 31 subjects developed preeclampsia by term; serum total magnesium levels decreased significantly by the second trimester in these women compared with those of normal pregnant women. Conclusion Our results provide evidence of decreases in ionized and total magnesium levels with increasing gestational age during normal pregnancy, as well as evidence of a magnesium disturbance in women who later develop preeclampsia. Future studies of magnesium balance in women at risk for developing complications of pregnancy are indicated.

Cellular-Free Magnesium Depletion in Brain and Muscle of Normal and Preeclamptic Pregnancy: A Nuclear Magnetic Resonance Spectroscopic Study

Preeclampsia is a pregnancy disorder of unknown origin, characterized by vasospasm, elevated blood pressure, and increased neuromuscular irritability, features common to syndromes of magnesium deficiency. Evidence of serum and ionized magnesium metabolism disturbances have been observed in women with preeclampsia. This and the therapeutic utility of magnesium in preeclampsia led us to investigate the extent to which an endogenous tissue magnesium deficiency might be present in and contribute to its pathophysiology. We used 31P nuclear magnetic resonance spectroscopy to noninvasively measure in situ intracellular-free magnesium levels in brain and skeletal muscle of fasting nonpregnant women (n=12), and of third trimester women with uncomplicated pregnancies (n=11) and preeclampsia (n=7). Compared with nonpregnant controls (brain 519±59 &mgr;mol/L; muscle 604±34 &mgr;mol/L), brain and skeletal muscle intracellular magnesium levels were significantly lower in both normal pregnant (brain 342±23 &mgr;mol/L; muscle 482±40 &mgr;mol/L; P=0.05 for both tissues) and preeclamptic women (brain 229±17 &mgr;mol/L; muscle 433±46 &mgr;mol/L; P=0.05 for both tissues). Brain intracellular magnesium was further reduced in preeclamptics compared with normal pregnant subjects (P=0.05). For all pregnant subjects, blood pressure was significantly and inversely related to the concomitantly measured intracellular magnesium level in brain (systolic, r=−0.59, P=0.01; diastolic, r=−0.52, P=0.02) but not in muscle. Cellular magnesium depletion is characteristic of normal pregnancy and may be one factor contributing to the pathophysiology of preeclampsia. Furthermore, the influence of central nervous system factors on blood pressure may be mediated, at least in part, by ambient intracellular magnesium levels.

Fetal ionized magnesium levels parallel maternal levels during magnesium sulfate therapy for preeclampsia

OBJECTIVE Little is known about ion regulation in fetuses. Our aim was to determine the effects of magnesium sulfate therapy on ionized (bioactive) magnesium in the cord blood of pregnancies complicated by preeclampsia. STUDY DESIGN Seventy-four pregnant women were studied (37 preeclamptic and 37 controls matched for maternal age, gravidity, and gestational age). The preeclamptic women received intravenous magnesium sulfate 6 gm load followed by 2 gm/hour for > or = 4 hours; controls were not preeclamptic and received no magnesium. Maternal venous and fetal cord blood samples were obtained from study and control patients and were analyzed for sodium, potassium, total magnesium, ionized magnesium, total calcium, and ionized calcium. Comparisons between the groups were made and analyzed by the Mann-Whitney U test. RESULTS There were no significant differences between the treatment and control group cord samples with respect to sodium or potassium. However, total magnesium and ionized magnesium were significantly elevated (p < 0.001) in cord samples of the treated group. At the same time ionized calcium and total calcium were reduced. Interestingly, ionized calcium levels were lower in preeclamptic women before magnesium sulfate therapy was begun, whereas total calcium levels were not different. Importantly, there was no difference between maternal and fetal ionized magnesium levels in either treatment or control groups. CONCLUSIONS In preeclamptic women undergoing magnesium sulfate therapy, ionized magnesium levels in cord blood parallel maternal levels. Before magnesium therapy ionized calcium levels were lower in preeclamptic women than in matched controls. In the presence of elevated magnesium levels ionized calcium appears to be tightly regulated.

Magnesium is more efficacious than phenytoin in reducing N-methyl-D-aspartate seizures in rats

OBJECTIVE Although magnesium sulfate is one of the most commonly used agents for seizure prophylaxis in preeclampsia, its efficacy relative to other anticonvulsants is incompletely investigated. The underlying mechanisms of eclamptic seizures are unknown, and there is currently no universally accepted animal model for eclampsia. However, one commonly used method for studying the relative efficacy of antiepileptic drugs is through their effect on N-methyl-D-aspartate-induced seizures. Our aim was to compare the anticonvulsant effects of phenytoin and magnesium sulfate in an N-methyl-D-aspartate-induced seizure model. STUDY DESIGN Twenty-one female rats were each stereotaxically implanted with a chronic indwelling bipolar recording electrode in the hippocampus and an injection cannula in the lateral cerebral ventricle. After 7 days animals were randomly given 90 mg/kg magnesium sulfate (n = 7), 50 mg/kg phenytoin, or saline solution (n = 7) intravenously. Fifteen minutes after the infusions animals were given 20 micrograms/microliters N-methyl-D-aspartate by direct intraventricular injection, and seizure activity was assessed for 20 minutes thereafter. All data were analyzed with the Mann-Whitney test. RESULTS When compared with saline solution controls, total duration of seizure activity in animals treated with magnesium sulfate was significantly decreased (p < 0.05) and time to onset of seizure activity was significantly increased (p < 0.05). However, rats that received phenytoin did not show significant changes in these parameters. The post-N-methyl-D-aspartate seizure mortality rate was 50% in the saline solution controls and 29% in the phenytoin group, whereas none of the rats that received magnesium sulfate died. CONCLUSION These results suggest that magnesium sulfate is a significantly more effective prophylactic agent than phenytoin for N-methyl-D-aspartate-induced seizures.

Differential regulation of seizure activity in the hippocampus of male and female rats

OBJECTIVE The aim of the current study was to directly examine and compare the susceptibility to N-methyl-D-aspartate-induced seizures in male versus female rats. We also sought to compare the anticonvulsant effects of magnesium sulfate in these two groups. STUDY DESIGN Eighteen female and 10 male rats were stereotaxically implanted with a chronic bipolar recording electrode in the hippocampus and an injection cannula in the lateral cerebral ventricle. After 1 week rats randomly received an intravenous injection of 90 mg/kg magnesium sulfate or saline solution control. Fifteen minutes after the infusion rats were given the convulsant N-methyl-D-aspartate at a dose of 5 micrograms/microliters by direct intraventricular injection. Electrical seizure activity was thereafter assessed for 20 minutes. All data were analyzed by the Mann-Whitney U test and Student t test. RESULTS In saline solution-treated rats receiving the convulsant N-methyl-D-aspartate, females had significantly lower total duration (p < 0.01) and total number of seizures (p < 0.05) compared with the male rats. The initial seizure was not affected by gender. In the female animals magnesium sulfate significantly reduced first seizure duration (p < 0.01) compared with saline solution controls. In males magnesium sulfate reduced both total duration (p < 0.05) and total seizure number (p < 0.05) compared with saline solution-treated animals. CONCLUSION N-methyl-D-aspartate-induced seizure activity is more severe in males versus female rats. Magnesium sulfates effect on N-methyl-D-aspartate-induced seizures is also dependent on gender. We speculate that seizure regulation may be hormonally influenced.

Serum ionized magnesium levels decrease with gestational age in normal pregnant women

193 SERUM IONIZED MAGNESIUM LEVELS DECREASE WITH GESTATIONAL AGE IN NORMAL PREGNANT WOMEN. ~ , J.E. Whitty, B.A. Mason, S.M. Irtenkauf*, D.B. Cotton. Department of Ob/Gya, Hutzel Hospital, Wayne State University. OBJECTIVE: Longitudinal changes in serum ionized magnesium. (IMg) and total magnesium (TMg) during pregnancy have not been adequately described. The aim of the present study was to determine levels of IMg, TMg, ionized calcium (ICa), sodium (NA), potassium (K) and pH values over the course of pregnancy in normal pregnant women. STUDY DESIGN: We obtained venous serum samples from 27 normal pregnant women during their first, second and third trimesters. Gestational ages ranged from 6-37 weeks. Samples were analyzed for IMg, TMg, ICa, Na, K and pH using a biomedical stat profile chemistry analyzer with specific ion sensitive electrodes. Data were analyzed with repeated measures ANOVA. RESULTS: In normal pregnant patients, beth serum IMg and TMg decreased linearly with increasing gestational age (p TERB > RITO. CONCLUSION: Similar K~ values and receptor responses support the use of mononuclear leukocytes as a model for I~adrenoreceptors in less accessible myometrium. (Supported by the ETSU Research Development Committee).