[Increased concentration of Na,K-pumps in skeletal muscles of patients with chronic obstructive lung disease. Significance of magnesium depletion and treatment with glucocorticoids]. / Forøget koncentration af Na,K-pumper i tvaerstribet muskulatur hos patienter med kronisk obstruktiv lungesygdom. Betydning af magnesiumdepletering og behandling med glukokortikoider.

Patients with COLD may develop Mg depletion due to inadequate nutrition or treatment with diuretics and beta 2-agonists. In 36 consecutive COLD patients skeletal muscle concentrations of Mg and K were reduced by 22% and 14%, respectively, compared to 23 age- and sex-matched controls (p < 0.001). Patients receiving diuretics showed a further reduction of muscle Mg (-31%) and K (-27%) compared to controls. The mean concentration of Na,K pumps was increased by 31% (p < 0.001), while a more pronounced increase (+61%) was seen in 12 intensive care patients receiving high dosages of glucocorticoids. Thus muscle concentrations of Mg and K are reduced in COLD patients and are associated with an upregulation of the Na,K-pump concentration. It is plausible that this upregulation may be caused by glucocorticoid treatment. The clinical benefits of glucocorticoids may therefore in part be due to an increased activity and capacity of the Na,K-pump and thereby in a possible enhancement of muscle force.

The concentration of sodium, potassium pumps in chronic obstructive lung disease (COLD) patients: the impact of magnesium depletion and steroid treatment.

OBJECTIVES: To evaluate the concentrations of magnesium (Mg), potassium (K) and sodium,potassium pumps (Na,K pumps) in skeletal muscle in patients with chronic obstructive lung disease (COLD) treated with or without diuretics. DESIGN: An open cross-sectional study. SETTING: COLD patients admitted to the Medical Department of Vejle Hospital, Denmark. SUBJECTS: Thirty-six consecutive COLD patients and 23 age- and sex-matched controls. MAIN OUTCOME MEASURES: Biopsies of skeletal muscle were performed in patients and controls for measurements of Mg, K and Na,K pumps. In a parallel animal experiment the influence of medical treatment on the concentration of Na,K pumps in skeletal muscle was evaluated by infusing 10-week-old rats for 14 days with vehicle, terbutaline, or dexamethasone. RESULTS: In the patients, mean muscle Mg and K concentrations were reduced by 22 and 14% respectively (P < 0.001), but in those patients who received diuretics muscle Mg and K were further reduced (by 31 and 27%, respectively, of the control values). The concentration of Na,K pumps was increased by 31% (P < 0.001), with a maximum increase of 61% (P < -0.001) in 12 intensive care patients receiving high dosages of glucocorticoids. Linear regression analysis showed a positive correlation between daily glucocorticoid intake and the concentration of Na,K pumps in the biopsy specimens from each patient (r = 0.38, P = 0.02). In the experimental study, dexamethasone induced 27-34% increase in the concentration of Na,K pumps (P < 0.01) in three different muscles, whereas there was no significant change following terbutaline infusion. CONCLUSIONS: COLD patients show reduced concentrations of Mg and K in skeletal muscle, associated with an upregulation of the Na,K pump concentration. It is plausible that this upregulation may be caused by glucocorticoid treatment. The clinical benefits of glucocorticoids may in part be due to an increase in the activity and capacity of the Na,K pump and thereby in a possible enhancement of muscle force.

Effects of K+, Mg2+ deficiency and adrenal steroids on Na+, K(+)-pump concentration in skeletal muscle.

Animal studies have shown that deficiency of K+ is associated with a reduction in the concentration of Na+, K+ pumps in skeletal muscle, and that this reduction is closely correlated with the reduction in the muscle K+ concentration. Furthermore, animals deficient in Mg+ show a downregulation of the Na+, K(+)-pump concentration, but this seems to be secondary to the concomitant K+ deficiency, which often accompanies Mg2+ deficiency. Measurements on skeletal muscle biopsies from patients who had been in long-term treatment with diuretics showed that 55% had reduced concentrations of both K+ and Mg2+, and that this was associated with a reduction in the concentration of Na+, K+ pumps. Furthermore, the Na+, K(+)-pump concentration correlated significantly with both muscle K+ and Mg2+, suggesting that the downregulation of the Na+, K+ pumps was related to the loss of K+, as predicted from the animal experiments. In accordance with this, normalization of muscle K+ and Mg2+ in response to oral Mg2+ supplementation, resulted in a restoration of the Na+, K+ pumps. Apart from thyroid hormone, which is another major regulator for the Na+, K(+)-pump concentration, other hormones may be of importance. It is well known that adrenal steroids control the synthesis of Na+, K+ pumps in the kidney and heart. Recently, treatment with dexamethasone was found to increase the Na+, K(+)-pump concentration in rat skeletal muscle. The increase was found in EDL, soleus, gastrocnemius and diaphragm muscles, and amounted to 23-52%. In contrast, treatment with aldosterone induced a decrease in the Na+, K(+)-pump concentration, which was closely correlated to the reduced K+ content of the muscles. The results indicate that in skeletal muscle, high doses of glucocorticoids upregulate the concentration of Na+, K+ pumps, whereas mineralocorticoids induce a downregulation which is secondary to the concomitant K+ deficiency.

[Oral magnesium supplementation to patients receiving diuretics--normalization of magnesium, potassium and sodium, and potassium pumps in the skeletal muscles]. / Peroralt magnesiumtilskud til patienter i diuretisk behandling--normalisering of magnesium, kalium og natrium, kalium-pumper i tvoerstribet muskulatur.

In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of magnesium, potassium, and sodium-potassium pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle magnesium and/or potassium below the control level received oral magnesium hydroxide supplement for 2-12 weeks (N = 20) or 26 weeks (N = 16). After short term (2-12 weeks) magnesium supplementation muscle parameters were increased, but far from normalized. After magnesium supplementation for 26 weeks, the muscle concentrations of magnesium, potassium and sodium-potassium pumps were normalized in most cases. Oral magnesium supplementation may restore diuretic-induced disturbances in the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle. A supplemental period of at least six months seems required before complete normalization can be expected.

Magnesium and potassium deficiency. Its diagnosis, occurrence and treatment in diuretic therapy and its consequences for growth, protein synthesis and growth factors.

Thiazides and loop diuretics facilitate the loss of K and Mg through the kidneys leading to deficiencies that may require treatment with supplements. These losses may be overlooked, however, because serum concentrations may remain normal even when the muscle concentrations are appreciably reduced. In 76 patients who had received diuretics for 1-17 years, the mean concentrations of K, Mg and Na,K-pumps in skeletal muscle biopsies were significantly lower than in those from an age- and sexmatched control group, and muscle Mg and K concentrations were significantly correlated. The serum concentrations, however, were only below the control range in a few patients. The fact that Mg,K deficiencies may often be overlooked emphasises the need for data on the contents of skeletal muscle. A recently developed simple biopsy needle procedure permitted the detection of disorders of electrolytes during long-term diuretic treatment despite normal serum concentrations. With the same technique it was possible to detect repletion of the muscle electrolytes after a Mg supplementation period. Oral Mg supplementation could reestablish normal Mg as well as K status in patients in long-term diuretic therapy, provided that the supplementation was maintained for 6 months. Moreover, the normalization of muscle Mg and K was accompanied by a restoration of the concentration of Na,K-pumps measured as the [3H]ouabain binding site capacity in skeletal muscle. Mg and K contents were closely correlated in human muscle biopsies from patients on diuretic treatment, but also in rat muscle which had been moderately Mg depleted in vivo or in vitro. In isolated soleus muscle, which had been moderately Mg-depleted in vitro, reduction in cellular K could not be ascribed to reduced Na,K-pump mediated K-influx. The reduced K content might rather be related to increased K efflux from the muscles. In rats, insufficient dietary supplies of K, Mg and Zn were characterized by inhibition of growth and protein synthesis. These effects could not readily be related to the loss of these elements from muscle tissue, but rather should be seen as a response to a general deficiency. The most marked evidence of deficiency was seen in the serum levels, which pointed to the serum concentration as a possible mediator for the regulation of tissue growth. IGF-I is a low molecular weight peptide possessing growth promoting properties in many tissues probably as an interplay of both autocrine/paracrine and endocrine actions. In both animals and man insufficient supplies of energy and protein are accompanied by growth retardation and a decrease in serum IGF-I.(ABSTRACT TRUNCATED AT 400 WORDS)

Energy and nutrient intakes in congenital heart disease.

Children with congenital heart disease may have significant growth retardation, which in part may be caused by insufficient dietary intake. Data on energy and nutrient intake were collected using a 14-day dietary record by weighing, in 22 children with congenital heart disease (mean age 39 months, range 12-126 months), prior to corrective operation. When viewed in relation to actual weight, energy intake averaged 88% (SD 17%) of that recommended by the FAO/WHO/UNU. Energy intakes and weight SD scores were significantly correlated (r = 0.55, p < 0.01). Protein intake was generally high, and even sufficient to allow catch-up growth. The majority of the children did not meet the recommendations for iron, zinc, calcium, or vitamins D, E, C, B1 or B6. Parents should be advised to give their children vitamin/mineral supplements, and to supply extra energy to children with failure to thrive.

Oral magnesium supplementation restores the concentrations of magnesium, potassium and sodium-potassium pumps in skeletal muscle of patients receiving diuretic treatment.

In 76 consecutive patients who had received diuretics for 1-17 years for arterial hypertension or congestive heart failure, muscle concentrations of magnesium, potassium, and sodium-potassium pumps were significantly reduced compared to 31 age- and sex-matched controls. Thirty-six patients with muscle magnesium and/or potassium below the control level received oral magnesium hydroxide supplement for 2-12 weeks (n = 20) or 26 weeks (n = 16). After short-term (2-12 weeks) magnesium supplementation muscle parameters were increased, but far from normalized. After magnesium supplementation for 26 weeks, the muscle concentrations of magnesium, potassium and sodium-potassium pumps were normalized in most cases. Oral magnesium supplementation may restore diuretic-induced disturbances in the concentrations of magnesium, potassium and sodium potassium pumps in skeletal muscle. A supplemental period of at least 6 months seems to be required before complete normalization can be expected.

Magnesium intake and status and pregnancy outcome in a Danish population.

OBJECTIVE: To investigate the relation between pregnancy outcome and magnesium intake and status. DESIGN: A prospective observational study in which the estimate of nutrient intake and serum samples were obtained before the final outcome of pregnancy was known. A second part of the investigation was a cross-sectional comparison of magnesium status of normal pregnant women and women with certain pathological pregnancies. SETTING: Antenatal clinic associated to the University Clinic of Obstetrics and Gynaecology, University of Aarhus, Denmark. SUBJECTS: 1203 consecutive women in the 30th week gestation were invited to participate in the study, 991 (82.4%) accepted and records for 965 (80.2%) were available for analysis. DATA: Food intake data were collected by a combination of a self administered questionnaire and a structured interview of a dietary history type. Serum samples were obtained from blood withdrawn in the 30th and 37th week gestation. Obstetric data were collected from the midwifery and hospital records. For a second part of the investigation, biopsies from the uterus and the abdominal rectus muscle were obtained from women delivered by caesarean section. RESULTS: In the women with normal pregnancies and in the three groups of pathological pregnancies (pre-eclampsia, SGA-infants and preterm labour) the average magnesium intake was within the range of 200 to 208 mg per 1000 kcal per day (SD 32) and there were no differences between the groups. Neither were differences in serum magnesium observed. Birthweight for gestational age was not influenced by magnesium intake. No differences in magnesium status as assessed by determination of magnesium content in muscle biopsies were found between the normal pregnancies and women with pre-eclampsia, SGA-infants or preterm labour. CONCLUSION: The intake of magnesium seemed adequate, and pre-eclampsia, SGA-infants, or preterm labour did not seem associated with a low dietary intake of magnesium or magnesium deficiency. Routine magnesium supplementation during pregnancy is not recommended for populations of relative good socio-economic status.

[Magnesium and long-term diuretic therapy]. / Magnesium og langvarig diuretikabehandling.

Thiazides and loop diuretics, facilitate the loss of Mg and K resulting in increased excretion in the urine. Although serum-K and serum-Mg values in patients receiving long-term treatment for hypertension or incompensated heart disease usually are normal, muscle-Mg and muscle-K contents are reduced in around 50% of these patients. Mg deficiency increases K loss and K/Mg deficiencies are frequently observed simultaneously. K repletion is often difficult if the accompanying Mg deficiency is not corrected simultaneously. The K/Mg loss from the muscles is accompanied by reduced concentration of Na,K-pumps. These disturbances may produce muscle symptoms, increased sensitivity to digitalis, inhibition of growth and possibly arrhythmias. Evaluation of the K and Mg status during diuretic treatment should be preferentially based on tissue determinations. The muscle biopsy method is rapid, reliable and may reveal conditions of deficiency. In several cases, oral supplements of Mg have proved to be adequate to restore the normal K/Mg status.

Reduced concentrations of potassium, magnesium, and sodium-potassium pumps in human skeletal muscle during treatment with diuretics.

Animal studies have shown that potassium depletion induced by diuretics or potassium deficient fodder leads to a selective decrease in the concentrations of potassium and in the concentration of sodium-potassium pumps in skeletal muscle. In 25 patients who had received diuretics for 2-14 years the mean concentrations of potassium, magnesium, and sodium-potassium pumps were measured in skeletal muscle biopsy specimens and were significantly lower than in those from a group of age matched controls. The reductions in all three variables were significant in those patients receiving diuretics for arterial hypertension as well as in those being treated for congestive heart failure. In 14 patients the mean muscle potassium concentration was below the control range, but only one of those was hypokalaemic (3.4 mmol/l), and 13 were receiving potassium supplements. In 15 patients the mean muscle magnesium concentration was below normal, and the mean muscle potassium and magnesium concentrations showed a linear correlation. In 12 patients in whom the mean muscle potassium concentration was below 80 mumol/g wet weight there was a linear correlation between the cellular potassium:sodium ratio and the concentration of 3H-ouabain binding sites indicating that potassium deficiency also leads to a down regulation of sodium-potassium pumps in human skeletal muscle. In spite of potassium supplements long term treatment with diuretics may lead to potassium and magnesium deficiencies, which are not detectable using the standard methods of serum analysis. The changes in concentrations of electrolytes and sodium-potassium pumps associated with treatment with diuretics may impair muscle function and potassium homoeostasis and interfere with the distribution of digitalis glycosides.