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Variations in the response of sheep to experimental magnesium deficiency.

Hypomagnesaemia was induced in adult sheep by changing their diet from chaff given orally to a milk diet, low in Mg, infused via the abomasum. All sheep given the milk diet developed hypomagnesaemia and four out of 19 developed nervous convulsions similar to the natural disease grass tetany. Analysis of the sequential changes in plasma Ca, P and Mg revealed a striking positive correlation between Ca and Mg and hypocalcaemia thus appeared to be a general response to Mg deficiency. Many sheep appeared to adapt to the deficiency since after a period of about 11 days the decline in plasma Mg (and Ca) was either alleviated or reversed. However the four sheep which developed convulsions all showed a rapid and substantial decline in plasma Mg associated with a decline in plasma Ca.

Animals↗

Magnesium deficiency in congestive heart failure.

In congestive heart failure several compensatory mechanisms are operating, and may cause severe disturbances of both the internal and external electrolyte balance. The medical treatment prescribed in congestive heart failure also leads to changes in the handling of electrolytes. These combined effects may prove critical to the patient, especially with regard to the emergence of cardiac arrhythmias.

Cardiac Output↗

Magnesium loading effect on magnesium deficiency in endurance-trained subjects during prolonged restriction of muscular activity.

The aim of this study was to evaluate the effect of magnesium (Mg) loading (10.0 mg Mg/kg body wt) and daily Mg supplements (5.0 mg Mg/kg body wt) on Mg deficiency shown by increased and not by decreased serum Mg concentration during hypokinesia (decreased km number/d). The studies were done during 30 d of prehypokinesia and 364 d of hypokinesia (HK) periods. Forty endurance-trained volunteers aged 22-26 yr with a peak VO2 max of 66.3 mL.kg-1 min-1 and with an average 15.0 km/d running distance were chosen as subjects. They were equally divided into four groups: 1. Unsupplemented ambulatory control subjects (UACS). 2. Unsupplemented hypokinetic subjects (UHKS). 3. Supplemented hypokinetic subjects (SHKS). 4. Supplemented ambulatory control subjects (SACS). The SHKS and SACS groups took daily 5.0 mg elemental Mg/kg body wt and subjected to Mg loading (10.0 mg Mg/kg body wt). Both the SHKS and UHKS groups were maintained under an average running distance of 4.7 km/d, whereas the SACS and UACS groups did not experience any modifications to their normal training routines and diets. During the prehypokinetic and hypokinetic periods, excretion of Mg in feces and urine, concentration of Mg in serum, and Mg balance were measured. Urinary and serum sodium (Na), potassium (K), and calcium (Ca) were also determined. In both SHKS and UHKS groups, fecal Mg loss, urinary excretion of electrolytes, and serum concentrations of electrolytes increased significantly (p < or = 0.05) when compared with the SACS and UACS groups. During Mg loading tests, urinary and fecal Mg excretion was also greater in the SHKS and UHKS groups than in the SACS and UACS groups. Throughout the study, Mg balance was negative in the SHKS and UHKS groups, whereas in the SACS and UACS groups, Mg balance was positive. It was concluded that significant losses of Mg occurred in the presence of negative Mg balance and Mg deficiency in endurance-trained subjects during prolonged exposure to HK, daily mg supplements, and Mg loading tests. This suggests that Mg is not entering or being retaining by the bones and cells of many tissues where most Mg is deposited normally, resulting in Mg deficiency as was shown by the increased serum Mg concentration.

Adult↗

Noninvolvement of histamine and prostaglandins in the dermatosis of magnesium-deficient hairless rats.

Hairless rats receiving a deprived Mg2+ diet developed long-lasting inflammatory dermatosis which was not influenced by treatments with mepyramine, cimetidine, aspirin or indomethacin. Dermatosis did not appear in deprived rats treated with intraperitoneal injections of Mg2+, or with dexamethasone. Histamine and prostaglandins did not seem to be involved in this dermatosis. The possible role of leucotrienes is discussed.

Animals↗

Magnesium deficiency in a pregnancy six years after jejunoileal bypass.

The following case report reviews the obstetrical course of a patient who had undergone a jejunoileal bypass six years prior to her pregnancy. Documentation of hypomagnesemia and parenteral treatment of this condition are reported along with the successful outcome. Bypass procedures may result in biochemical aberrations which affect pregnancy outcome. The implications of such surgery is reviewed as well as its current status.

Adult↗

Intestinal and cardiac inflammatory response shows enhanced endotoxin receptor (CD14) expression in magnesium deficiency.

Substance P is elevated in plasma and in other tissues during Mg-deficiency, and was found localised to neuronal C-fibres of cardiac and intestinal tissues, where it could promote neurogenic inflammation. Plasma prostaglandin E2 (PGE2), indicative of systemic inflammation, rose significantly (>or=4 fold, p<0.01) after 1 week and remained elevated through week 2 and 3 in rat on the Mg-deficient (MgD) diet. Concomitantly, total blood glutathione decreased by 50%. Immunohistochemical staining for endotoxin (lipopolysaccaride, LPS) receptor, CD14 was prominent in macrophage-type cells in intestinal tissue; more importantly, cardiac tissue revealed both CD11b (monocyte/macrophage surface protein) and CD14 positive cells after 3 weeks in rats on MgD diet. Western blot analysis indicated a significant increase in the endotoxin receptor protein level in the 3 week MgD hearts. Since CD14 is known to be up-regulated in cells exposed to LPS, these observations suggest that prolonged Mg-deficiency results in increased intestinal permeability to bacterial products that induce the endotoxin receptor in cells localized to myocardial and intestinal tissues. These CD14 positive cells may amplify the cardiomyopathic inflammatory process by stimulating TNF-alpha and other pro-inflammatory cytokines.

Animals↗

[Increase of connective tissue in rat hearts under exposure to noise and with magnesium deficiency (author's transl)].

Only a small amount of noise caused, combined with a nutritional Mg deficiency, a significant increase of collagen in the myocard of rats. While Mg deficiency or noise each for its own had no effect, the combination of both had a noxious effect. The results of these experiments give a hint to a correlation between collagen-increase in the myocard and an increase of urinal Catecholamine during the same time.

Animals↗

Development and properties of malignant lymphoma induced by magnesium deficiency in rats.

Female wistar rats were fed on an Mg-deficient diet. After 8 to 10 weeks, the thymus glands were strongly degenerated and the number of lymphocytes was reduced, especially in the cortex. Thymus degeneration was associated with a decreased rate of DNA, RNA, and protein biosynthesis and necrosis and phagocytosis of lymphocytes. The degeneration was normalized after feeding on an Mg-rich diet. After 10 or 11 weeks of Mg deficiency, local cell proliferations of immature lymphocytes with a great number of free ribosomes were found in some thymus glands. The local cell proliferations developed into infiltrating tumors without metastases. In lymphoma cells the Na+ and Ca2+ content, the turnover of cellular Na+ and K+, and the aerobic production of CO2 and lactate were increased.

Animals↗

Enzyme histochemistry of malignant T cell lymphoma due to chronic magnesium deficiency in rats.

The lymphocytes of the rat thymus can be grossly differentiated by their cell membrane-bound proteinases. Subcapsular thymocytes lack aminopeptidase A (APA) and AMP and gamma-glutamyltranspeptidase (GGT). Cortical thymocytes show a high activity of APA but no APM and no GGT. Medullar thymocytes possess a high GGT and APM activity but are free of APA. Under Mg deficiency, the APA-negative subcapsular thymocytes are reduced. In lymphoma and beginning lymphoma, APA, APM and GGT are absent. In lymphoma, the alkaline phosphatase activity is increased. Differences are found for dipeptidylpeptidase IV (DPP IV). In some lymphoma, its activity is reduced, in others the DPP IV activity is increased.

Alkaline Phosphatase↗

Cytokines, neuropeptides, and reperfusion injury during magnesium deficiency.

In summary, hypomagnesemia enhances reperfusion injury. We postulate that neurogenic inflammation, which occurs very early during hypomagnesemia, predisposes the myocardium to reperfusion injury by depleting endogenous antioxidants and recruiting inflammatory cells, which can participate in enhanced free radical production during postischemic reperfusion. Vitamin E supplements can prevent the occurrence of this enhanced injury possibly through the restoration of endogenous antioxidant defenses.

Animals↗

The effect of a magnesium deficient diet and cortisone on the growth of the rat incisor.

Incisors of Mg-deficient rats showed a marked inhibition of eruption and a decrease in mitoses of apical tissues. Cortisone administration resulted in some increase in eruption rate and cell division though these remained below the values of Mg-supplemented controls. An improvement in gross condition and a less severe histopathology of incisor tissues were also observed in cortisone-treated rats.

Animals↗

The myth of long-term thiazide-induced magnesium deficiency.

A group of 8 patients with essential hypertension and 12 patients with recurrent renal calcium stones were treated with 50 mg hydrochlorothiazide daily for a period of 3-10 years. Serum, erythrocyte, lymphocyte, skeletal muscle, bone and urine Mg were found to be within the normal range. In the intravenous Mg load test, all patients retained a normal percentage of the loading dose of Mg. Long-term thiazide therapy does not appear to lead to Mg depletion.

Bone and Bones↗

Relationship of bone and plasma magnesium in magnesium-deficient cirrhosis patients.

Total and ionized plasma Mg levels and cortical and trabecular bone Mg concentration were determined in five untreated nonalcoholic cirrhosis patients with ascites and edema. The high peripheral renin activity and serum aldosterone proved the existence of secondary aldosteronism in these patients. Total plasma Mg and trabecular bone Mg were within normal limits. A decreased absolute level and percentage of ionized plasma Mg were found without hypoalbuminemia, and cortical bone Mg concentration was decreased. Ionized plasma Mg concentration correlated closely with cortical bone Mg concentration when the levels of bone and plasma Mg were below normal.

Ascites↗

Membrane alterations in magnesium-deficiency-induced malignant T cell lymphoma.

Malignant T cell lymphoma cells induced in the thymus by chronic Mg deficiency showed a less ruffled surface in the scanning electron microscope, particularly after intraperitoneal transplantation. Their content of phosphatidylserine and phosphatidylinositol was increased. The content of phosphatidylcholine, cholesterol and the cholesterol/phospholipid ratio, and thus membrane microviscosity, were decreased. The activity of phospholipid methyltransferase I and II was reduced. In parallel to these alterations, 45Ca2+ influx and efflux as well as 45Ca2+ content in mitochondria, microsomes and cytosol of lymphoma cells were enhanced.

Animals↗

Magnesium deficiency in the pathogenesis of mitral valve prolapse.

Idiopathic mitral valve prolapse (MVP) is the commonest valvular disorder in industrialized nations. It is predominantly a familial condition, showing Mendelian dominance with delayed and variable penetrance. Although hyperkinesis and hypertrophy of the left ventricle have been described in MVP, its histopathology, somatic morphology and genetics support the leading theory that MVP results from a hereditary disorder of connective tissue. Latent tetany (LT) due to chronic Mg deficit (Mg-D) occurs in over 85% of MVP cases; MVP complicates 26% of LT. Mg-D can explain many clinical features of the MVP syndrome which are not easily explained by its genetics. Mg-D hinders the mechanism by which fibroblasts degrade defective collagen, increases circulating catecholamines, predisposes to cardiac arrhythmias, thromboembolic phenomena and dysregulation of the immune and autonomic nervous systems. Mg therapy provides relief of MVP symptoms.

Alprostadil↗

The effect of magnesium deficiency on volatile anaesthetic requirement in the rat: the role of central noradrenergic neuronal activity.

Volatile anaesthetic minimum alveolar concentration (MAC, a measure of anaesthetic requirement) increased in a time-dependent manner in rats fed a Mg2+-deficient diet. MAC values in hypomagnesemic rats were 22-30 per cent greater than those in age-matched controls at 12 and 17 days after starting the diet (p < 0.01). Noradrenergic neuronal activity, as assessed from the ratio of the concentration of 3,4-dihydroxyphenylethylene-glycol (DHPG) to that of norepinephrine (NE), decreased in the brain stem and cerebrum-cerebellum in hypomagnesemic rats owing to an increase in NE concentration in both regions of the brain (p < 0.025). We conclude that prolonged hypomagnesemia (> or = 12 days) increases volatile anaesthetic MAC in the rat. The concomitant decrease in the ratio of DHPG/NE suggests that this increase in MAC cannot be attributed to an increase in noradrenergic neuronal activity in brain.

Anesthetics, Inhalation↗

Acute extracellular magnesium deficiency and myocardial tolerance to ischemia.

The present study was undertaken in order to assess the effects of an acute and purely extracellular depletion of Mg during subtotal global ischemia and/or during post-ischemic reperfusion in the isolated rat heart. Mg depletion during reperfusion only or during ischemia plus reperfusion induced a significant reduction in post-ischemic recovery of cardiac function. Mg depletion during ischemia alone induced only a minor reduction in inotropy and coronary flow. Myocardial ATP at the end of the experiment was lowered in the groups of hearts deprived of Mg during ischemia plus reperfusion or during reperfusion only. A secondary finding was the demonstration of positive chronotropic and negative inotropic effects of the removal of extracellular Mg in non-ischemic hearts. It is concluded that, in a minor to moderate ischemic injury as in the present study, acute removal of extracellular Mg may lead to impairment of post-ischemic cardiac function and metabolism.

Adenosine Triphosphate↗

Pathobiology of magnesium deficiency: a cytokine/neurogenic inflammation hypothesis.

During the progression of Mg deficiency in a rodent model, we have observed dramatic increases in serum levels of inflammatory cytokines [interleukin-1 (IL-1), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] after 3 wk on a Mg-deficient diet. Sequential analyses of these cytokine changes in the serum of rats revealed an initial rise at day 12, followed by a major elevation in all three cytokine levels by day 21. Of greater interest was an early peak in the serum level of the neuropeptide substance P after only 5 days on the diet. This "neuronal" tachykinin is thought to be released from neural tissues, and it is known to stimulate production of certain cytokines, including IL-1, IL-6, and TNF-alpha. In addition, there was a concomitant increase in histamine levels, which may have resulted from stimulation and degranulation of mast cells by substance P. Thus we hypothesize that the release of substance P may be the earliest pathophysiological event leading to stimulation of the inflammatory cytokines, which may then stimulate the free radical mechanisms of injury previously confirmed by our work.

Animals↗