Relation of cardiovascular disease to potassium and magnesium deficiencies.

Potassium and magnesium deficiencies, particularly those induced by conventional loop and thiazide diuretic therapy, have been linked in clinical studies to an increased frequency in serious arrhythmias and mortality in acute myocardial infarction. Magnesium repletion has been shown not only to increase magnesium levels, but also to increase muscle potassium and to decrease the frequency of ventricular ectopic beats. Potassium replenishment alone may have a detrimental effect in magnesium-depleted patients. The potassium-sparing diuretic spironolactone (Aldactone) has been shown to spare both potassium and magnesium, and may therefore be a more appropriate diuretic therapy in patients at cardiovascular risk.

Muscle magnesium and capillary basement membrane thickness in diabetes mellitus.

To evaluate a possible relationship between Mg deficiency and the development of microvascular disease in diabetes mellitus, quadriceps muscle biopsies for estimating Mg content and capillary basement membrane thickness, were studied in 16 patients with type I diabetes. The diabetic individuals had a slightly but significantly reduced muscle Mg content as compared with 13 healthy controls. There was a significant, positive correlation between capillary basement membrane width and age in the diabetic group, but no relationship between membrane thickness and muscle or serum concentration of Mg. However, diabetic patients with retinopathy (n = 6) showed a nonsignificant inverse correlation between basement membrane thickness and Mg parameters. The opposite tendency was found in patients without retinal lesions.

Effects of peroral magnesium on plasma and skeletal muscle electrolytes in patients on long-term diuretic therapy.

Twenty patients on long-term diuretic therapy for arterial hypertension and/or congestive heart failure were given a supplementary dose of 15 mmol magnesium aspartate hydrochloride per day for 6 months. Nineteen patients, fulfilling the same admission criteria as the treatment group, served as controls. The addition of magnesium aspartate hydrochloride resulted in a significant rise of the cellular potassium and magnesium content and in a significant decrease of both systolic and diastolic blood pressure. It is concluded that supplementation with magnesium aspartate hydrochloride may effectively prevent the diuretic induced disturbances of electrolyte balance.

Amiloride prevents thiazide-induced intracellular potassium and magnesium losses.

To study the effect of a combination of amiloride, 5 mg, and hydrochlorothiazide, 50 mg (Moduretic), on plasma and skeletal muscle electrolytes in patients on long-term diuretic therapy (greater than 1 year) for arterial hypertension and/or congestive heart failure, 58 patients were recruited. Fifty-five patients completed the study, 27 controls and 28 in the treatment group. The Moduretic group demonstrated a significant increase in skeletal muscle potassium and magnesium values and a significant decrease in systolic blood pressure after 6 months on therapy. There was no significant change in these parameters in the control group. It is concluded that this combination of amiloride and hydrochlorothiazide is capable of preserving the internal and external balance of potassium and magnesium on a long-term basis in the patient categories studied.

Effects of triamterene on serum and skeletal muscle electrolytes in diuretic-treated patients.

The effects on plasma and skeletal muscle electrolytes of the combination of triamterene 37.5 mg and hydrochlorothiazide 25 mg daily were studied in 19 patients on prior long-term (greater than 1 year) diuretic therapy for arterial hypertension and/or congestive heart failure. A further 20 patients fulfilling the same admission criteria were used as controls. Blood samples and skeletal muscle biopsies were taken before the study and after 6 months on therapy. The diuretic-treated group had a significant increase in skeletal muscle potassium and magnesium after 6 months on therapy as compared to the controls. Thus, the combination of triamterene and hydrochlorothiazide appeared effective in preserving the cellular content of potassium and magnesium on a long-term basis in the type of patient studied.

Magnesium and hypertension.

Essential hypertension (EHT) is one of the most common risk factors for cerebrovascular and cardiovascular disease (CVD), which in turn are among the most common causes of death and disability in developed countries. Drug treatment of EHT has proven effective in lessening the risk of CVD, but has attendant risk of side effects, some of which are of risk to the CV system. Thus, increasing attention is being paid to non-drug treatment of EHT, which includes changing the daily intake of such electrolytes as sodium (Na), potassium (K), calcium (Ca), and magnesium (Mg). Decreasing Na intake to control blood pressure (BP) is well established. On the basis of epidemiologic and experimental studies, increasing K and/or Mg intakes, and increasing of decreasing Ca intakes, have each been proposed to have beneficial effects of BP. Presented here is a review of the background data supporting the rationale for adding Mg to the anti-hypertensive regimen. There is evidence that Mg can exert a favorable effect in EHT, particularly when used in combination with K during diuretic therapy.

Potassium/magnesium depletion in patients with cardiovascular disease.

Diuretic-induced deficiencies in potassium and magnesium can have significant implications for patients with cardiovascular disease. Hypokalemia, found in up to 50 percent of patients receiving thiazide therapy, is associated with a greater frequency of serious arrhythmias and increased mortality in patients with acute myocardial infarction. Hypomagnesemia has been identified in 42 percent of patients with hypokalemia, and below normal muscle magnesium levels have been found in 43 percent of congestive heart failure patients receiving diuretics. Magnesium is important for maintenance of cell potassium, and infusions of magnesium alone have increased muscle potassium and magnesium levels and significantly decreased the frequency of ventricular ectopic beats. It has been shown that both potassium and magnesium are conserved by potassium-sparing agents. Because serum and tissue magnesium levels are not correlated and correlations for potassium levels are weak, prevention of these electrolyte abnormalities is advised.

Plasma and skeletal muscle electrolytes in patients on long-term diuretic therapy for arterial hypertension and/or congestive heart failure.

Investigations regarding plasma and skeletal muscle electrolytes were carried out in 537 patients on long-term diuretic treatment (greater than 1 year) for arterial hypertension (n = 240) and/or congestive heart failure (n = 297). In both groups there were significant decreases in both plasma and skeletal muscle K and Mg, while the muscle Na values as well as the total and extracellular water content of skeletal muscle were increased.

Potassium-sparing diuretics.

The hemodynamic and the endocrine disturbances in congestive heart failure (CHF) impose major changes in electrolyte balance with a retention of sodium and concomitant losses of potassium and magnesium from the body. These changes are of great importance for the development of cardiac dysrhythmias, a diminished glucose tolerance and for the well-being of the patient. The use of conventional diuretics imposes further burdens on the already deranged electrolyte balance. On long-term therapy with conventional diuretics in CHF we observed that approximately 50% of the 297 patients studied had potassium and magnesium deficiencies and an increased sodium content as judged by skeletal muscle biopsies. The magnesium deficiency is especially dangerous since it prevents the cells from keeping their high intracellular potassium concentration unchanged. Potassium substitution is without effect in a magnesium deficiency since magnesium is necessary for the transportation of potassium over the cell membrane against the concentration gradient. In case of magnesium depletion, potassium substitution may even have negative effects on the body potassium content. The reason for this is probably the increase of p-potassium concentration induced by the substitution, leading to an increase of aldosterone secretion. An increase of p-potassium levels by 0.2-0.4 mmol/l may thus result in a 50-100% rise in p-aldosterone concentration. These changes promote further urinary losses of potassium and magnesium. Several studies have demonstrated the positive effects of the potassium-sparing diuretics amiloride, spironolactone and triamterene on p-potassium concentration, but also on the body potassium content.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt and water balance in congestive heart failure.

The majority of symptoms related to congestive heart failure (CHF) can be derived from the excessive accumulation of fluid in the body. The retention of fluid is the result of the activation of a complex system of compensatory mechanisms working on the kidneys and altering the hemodynamic situation in the body. The compensatory mechanisms are essentially the same as those activated in acute blood loss. The common denominator for CHF and acute blood loss is a decrease of the effective arterial blood volume (EABV), a parameter defined as blood volume in relation to vascular capacity. In the early stages of CHF there is an increased sympathoadrenergic tone, leading to a peripheral vasoconstriction and a decrease of blood flow to the kidneys. Due to a preferential constriction of the efferent arterioles, the filtration fraction is increased and the glomerular filtration rate remains unchanged. However, there is an increased colloid osmotic pressure and a decreased intravascular hydrostatic pressure in the peritubular capillaries. These alterations result in an increased reabsorption of sodium and water in the kidneys. Furthermore, the blood flow in the kidneys is rerouted from the cortical to the juxtamedullary nephrons, which have larger glomeruli and longer loops of Henle. This will further increase the retention of salt and water. The renin-angiotensin-aldosterone (R-A-A) system is also activated due to the decrease of EABV. Angiotensin II exerts about the same effects as norepinephrine--vasoconstriction, rerouting of blood within the kidney and preferential vasoconstriction of the efferent arterioles--all changes contributing to the retention of salt and water.(ABSTRACT TRUNCATED AT 250 WORDS)

Intracellular electrolytes in cardiac failure.

In congestive heart failure (CHF) there are several compensatory mechanisms operating which may influence electrolyte metabolism. The activation of the renin-angiotensin-aldosterone system causes retention of sodium (Na) and losses of potassium (K) and magnesium (Mg). The secondary hyperaldosteronism may give rise to high intracellular Na and low intracellular K through a direct permeability effect on the cell membrane. The Mg deficiency may lead to a further increase of intracellular Na and decrease of intracellular K since Mg is a necessary ion for the function of the Na-K pump. In 297 patients with diuretic treated CHF we found that 42% had hypokalemia, 37% hypomagnesemia and 12% hyponatremia. We also found that 57% had excess muscle Na, 52% had depletion of muscle K and 43% had low muscle Mg. We have also shown that the low muscle K cannot be corrected by K supplementation when there is a concomitant Mg deficiency and that Mg infusions may change the disturbed relation between extra- and intracellular electrolytes towards normal.

Peroral glucose tolerance test. Relation to skeletal muscle electrolytes.

Seventy patients on long-term diuretic therapy for arterial hypertension and/or congestive heart failure were investigated with regard to skeletal muscle electrolytes and the results of a peroral glucose tolerance test. A significant correlation was observed between the muscle content of potassium and the ability to handle a glucose load. Thirty patients underwent a second set of samples six months after the first one, 23 of whom had a reduction of their muscle potassium content relative to the first biopsy. They simultaneously demonstrated a significant impairment of glucose tolerance.

Effects of spironolactone on serum and muscle electrolytes in patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension.

The effect of adding spironolactone (Aldactone) on muscle electrolytes was studied in 48 patients with arterial hypertension and/or congestive heart failure who had received conventional diuretic treatment, including a potassium supplement, for more than 1 year. After 6 months on spironolactone 100 mg/day as well as the original conventional diuretic therapy, there was a significant increase in both skeletal muscle potassium and magnesium. At the same time these parameters decreased in the control group. In the spironolactone group there was also a significant increase in the mean serum potassium and creatinine levels. There was a significant fall in blood pressure in the spironolactone-treated group.

Renal excretion of electrolytes in patients on long-term diuretic therapy for arterial hypertension and/or congestive heart failure.

Renal excretion, skeletal muscle content and plasma concentration of electrolytes were studied in 108 patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension. As reference populations served a group of 16 healthy volunteers and a group of 22 patients with liver cirrhosis, but not on diuretic therapy. Diuretic therapy was found to deprive the patients of their ability to conserve potassium and magnesium when there was a simultaneous cellular depletion of these ions. Magnesium excretion was found to be correlated to the skeletal muscle magnesium content. An inverted Na/K ratio in urine and a low magnesium excretion were fair indicators of cellular magnesium depletion.

Skeletal muscle magnesium and potassium determinations: correlation with lymphocyte contents of magnesium and potassium.

Following a lymphocyte separation technique, the lymphocyte content of magnesium and potassium was determined by atomic absorption spectroscopy in 28 subjects. Simultaneously, skeletal muscle biopsies were obtained by a percutaneous technique and analyzed for magnesium and potassium. In this study there was not significant correlation between the lymphocyte and the skeletal muscle content of magnesium or potassium, except in the group of three normal volunteers and nine patients with mild arterial hypertension.

Aggravation of thiamine deficiency by magnesium depletion. A case report.

A patient with Crohn's disease and long-standing diarrhea resulting in a combined thiamine and magnesium deficiency is presented. Despite massive doses of thiamine i.v., the symptoms of thiamine deficiency could not be suppressed until the magnesium deficiency was corrected as well. This case report emphasizes the dependence of thiamine on magnesium for an adequate function in the body.

Plasma and skeletal muscle electrolytes in patients with Crohn's disease.

Plasma and skeletal muscle electrolytes were measured in 13 patients with Crohn's disease, and in an age- and sex-matched reference group. Patients with Crohn's disease demonstrated significantly lower muscle potassium content (p less than 0.01) than did controls. Patients with extensive involvement of the bowel tended to have lower muscle potassium content. The patient population did not differ significantly from the controls with regard to skeletal muscle magnesium content but displayed a far wider range of values. Our results indicate that potassium depletion is present in nonresected patients with Crohn's disease.

Intracellular magnesium loss after diuretic administration.

Diuretic agents influence the renal handling of magnesium, causing increased losses of the ion. Continuing magnesium losses may, in the long term, result in a magnesium deficiency. 296 patients with congestive heart failure or arterial hypertension receiving long term diuretic therapy were studied by skeletal muscle biopsies to assess their magnesium status. 65% of the congestive heart failure patients and 42% of the patients with arterial hypertension were found to have subnormal values for skeletal muscle magnesium. Studies with the potassium-sparing diuretics amiloride, spironolactone and triamterene demonstrate that these drugs significantly increase the muscle magnesium content in patients on long term diuretic treatment for congestive heart failure and/or arterial hypertension--in addition to their well known positive effect on potassium balance.