Cynthia A. Standley

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.

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.

Adrenomedullin Levels in Normal and Preeclamptic Pregnancy at Term

Objective: To describe maternal plasma levels of adrenomedullin (AM), a hypotensive and natriuretic peptide, in normal and preeclamptic women at term. Study design: Maternal plasma AM levels were determined in 13 preeclamptic and 15 normotensive primigravidas by radioimmunoassay. Plasma samples were obtained with the patients in the lateral recumbent position before the administration of any medications. Results: Women with preeclampsia had significantly elevated AM levels when compared with normotensive controls (42.3 ± 10.5 pg/mL versus 16.9 ± 3.1 pg/mL, P < .011). Conclusion: In this pilot study, AM levels were significantly increased at term in preeclamptic women.

N-methyl-D-aspartate receptor binding is altered and seizure potential reduced in pregnant rats

The objective of this study was to determine if a change in brain tissue excitatory amino acid receptor binding occurs during pregnancy using in vitro quantitative autoradiography and to examine seizure potential during pregnancy via central injection of N-methyl-D-aspartate (NMDA). For the receptor autoradiography studies, eight pregnant rats (day 21) and eight non-pregnant rats were euthanized with carbon dioxide, perfused, their brains dissected and frozen. Cryostat sections were taken and labeled in vitro by one of the following ligands: [3H]-CGP 39653, [3H]-glycine, [3H]-MK-801, [3H]-2-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) or [3H]-kainate. Optical density measurements of binding in 11 brain regions were performed using image analysis. To test seizure susceptibility, 74 rats were surgically implanted with an electrode into the hippocampus and a cannula into the lateral ventricle. Rats were mated; others served as non-pregnant controls. On gestational day 20, rats were randomized to receive no drug or an injection of NMDA (34, 68 or 136 nmol) through their indwelling cannulae. Seizures were assessed for 20 min. During pregnancy, the density of the NMDA competitive antagonist site measured by [3H]-CGP 39653 was decreased in the hippocampus, thalamus and hypothalamus (P<0.01), while the glycine modulation site was decreased in the cortex, hippocampus, thalamus, caudate and cerebellum (P<0.01). Kainate binding was significantly decreased in the hippocampus (P<0. 05). Total seizure duration and total number of seizures were significantly reduced in pregnant vs. non-pregnant rats (P<0.05). Pregnancy is associated with a significant alteration of NMDA and non-NMDA receptor binding in rats. These findings suggest that pregnancy affords some protection against seizures induced by an activation of NMDA receptors in the brain.

Anticonvulsant effects of magnesium sulfate in hippocampal-kindled rats

The objective of the present study was to determine whether magnesium sulfate has anticonvulsant actions in the hippocampal-kindled rat model of epilepsy. Fully kindled rats received acute intraperitoneal injections of magnesium sulfate (270 mg/kg), phenytoin (20 mg/kg) or saline in random order. Electrical seizure duration, behavioral seizure stage and duration of postictal EEG depression were examined 15, 30 and 60 min after injection. In an additional group of rats, kindled seizures were measured before and after chronic (2 h) intraperitoneal injections of magnesium sulfate versus saline. There was a significant decrease in electrical seizure duration (p < 0.01) and behavioral seizure stage (p < 0.01) with acute magnesium sulfate injections compared to saline injections. Phenytoin had no statistically significant effects on hippocampal-kindled seizures. Chronic magnesium sulfate treatment significantly reduced behavioral seizure stage at 2, 24, and 48 h postinjection (p < 0.05), but did not affect seizure duration. There was a significant time by treatment effect for magnesium sulfate on postictal EEG depression (p < 0.01). We conclude that in this model of hippocampal epilepsy-induced (kindled) rats, magnesium sulfate has significant anticonvulsant effects. Copyright 1995 S. Karger AG, Basel

Brain ionized magnesium and calcium levels during magnesium supplementation and deficiency in female Long-Evans rats.

Objective To examine the effect of changes in the state of magnesium balance on ionized magnesium and ionized calcium in serum and brain tissue of female rats. Methods Forty-two mature rats were used in the study. To induce hypermagnesemia, 12 rats received 270 mg/kg of magnesium sulfate intraperitoneally, followed every 20 minutes for 2 hours with 27 mg/kg magnesium sulfate. Ten control rats received an equal volume of saline. To induce hypomagnesemia, ten rats were placed on a magnesiumdeficient diet for 4 (n = 5) or 8 (n = 5) days. Ten control rats were placed on basal diets of equal duration. Following treatment, rats were euthanized and serum and brain tissue were analyzed for ionized magnesium and calcium content. Results Hypermagnesemia produced a significant increase in serum ionized magnesium (P <.05) and calcium (P <.05). In addition, brain levels of ionized magnesium were significantly increased (P <.05), whereas calcium levels significantly decreased (P <.05) particularly in the hippocampus, parietal cortex, and cerebellum. Hypomagnesemia induced by 4 days on a magnesium-deficient diet led to decreased serum ionized magnesium (P <.01) and total magnesium (P <.05) but did not affect brain magnesium levels. Brain levels remained unaltered even after 8 days of hypomagnesemia. Serum and brain ionized calcium were not affected during peripheral magnesium deficiency. Conclusion During peripheral magnesium deficiency, brain levels of ionized magnesium and ionized calcium are tightly regulated and appear unaffected. However, central levels of these electrolytes are altered under hypermagnesemic conditions. Thus, magnesium administration may change biologically active portions of magnesium and calcium in the brain.

Adrenomedullin levels in normal and preeclamptic pregnancies at term

OBJECTIVE To describe maternal plasma levels of adrenomedullin (AM), a hypotensive and natriuretic peptide, in normal and preeclamptic women at term. STUDY DESIGN Maternal plasma AM levels were determined in 13 preeclamptic and 15 normotensive primigravidas by radioimmunoassay. Plasma samples were obtained with the patients in the lateral recumbent position before the administration of any medications. RESULTS Women with preeclampsia had significantly elevated AM levels when compared with normotensive controls (42.3 +/- 10.5 pg/mL versus 16.9 +/- 3.1 pg/mL, P < .011). CONCLUSION In this pilot study, AM levels were significantly increased at term in preeclamptic women.

Maternal Electrical Seizures Are Associated with an Increase in Perinatal Death in Rat Pups

Relatively few investigators have examined the effect of pregnancy on seizure susceptibility. The present study was designed to determine whether there are any changes in hippocampal seizure thresholds during different stages of pregnancy. Second, we examined the effect of maternal seizures on perinatal mortality.Sixteen female rats were surgically anesthetized and a bipolar electrode stereotaxically implanted into the dorsal hippocampus. Following 1-week recovery, baseline values for seizure threshold were obtained for all rats. Seizure thresholds were then re-determined on days 7, 14, and 21 from baseline. Rats were then mated, and seizure thresholds again re-determined at days 7, 14, and 21 of pregnancy. Vaginal smears were taken 3 times weekly to determine stage of estrus on days stimulated during nonpregnancy. The amount of electrical current required to initiate a hippocampal seizure significantly decreased across each of the three stimulations before pregnancy (P <. 01). Vaginal smears indicated th...