Rational for Measuring IntraCellular Magnesium:

• Measurements of serum magnesium do NOT accurately assess tissue stores (1-see research ref. below and our research page).

• Magnesium is predominately an INTRACELLULAR ION and less than 1% of total body magnesium is found in the serum or plasma. (2)

• NO correlation exists between serum magnesium levels and heart muscle cells.

• Although the serum levels may appear normal, the tissue levels could commonly have subnormal levels of magnesium. Serum levels are maintained within a tight range. The measurement of magnesium in serum has  limited medical significance, but tissue levels reflect what is actually  happening in the working cells of the body.

• Direct assessment of Mg2+, (EXATEST), provides information NOT obtainable through routine serum electrolyte measurements. (3)(4)(5)(6)

1. Dyckner T. Wester PO. The relation between extra- and intracellular electrolytes in patients with hypokalemia and/or diuretic treatment. Acta Med Scand. 1978;204:269-282.

2. Eisenberg MJ. Magnesium deficiency and sudden death. Am Heart J. 1992; 124:544-549.

3. Haigney, Mark CP; Silver, Burton PhD.; Tanglao, Emmanuel MD; Silverman, Howard, S. MD; Hill, Donald, J. MD; Shapiro, Edward MD; Gerstenblith, Gary MD; Schulman, Steven, P. MD. Noninvasive Measurement of Tissue Magnesium and Correlation With Cardiac Levels. Circulation Vol 92, No. 8;2190-2197.

4. VII International Symposium On Magnesium. Presented by John Hopkins Department of Cardiology and IntraCellular Diagnostics, Inc. Athens, Greece, 1997.

5. Haigney, Mark C.P. MD. Silver, Burton, PhD. Et Al. Loss of Cardiac Magnesium in Experimental Heart Failure Prolongs and Destabilizes Repolarization in Dogs. Loss of Cardiac Magnesium in Experimental Heart Failure Prolongs and Destabilizes Repolarization in Dogs. American College of Cardiology. JACC Vol. 31, No.3 March 1, 1998:701-6

6. Haigney, Mark C.P. MD. Silver, Burton, PhD. Et Al. Tissue Magnesium Levels and the Arrhythmic Substrate in Humans.Journal of Cardiovascular Electrophysiology, Volume 8. No.9, September 1997. Copyright 1997 Futura Publishing Company, Inc. Armonk, NY

The Pharmacology Of Magnesium

As a bivalent cation, magnesium tends to form chelates (from the Greek chele = crabs claws).

The most important intracellular binding partner is ATP (adenosine triphosphate). Via chelation, large number of ATP-dependent enzymes, i.e. which promote cellular metabolism, are activated.

The First Effect Of Magnesium

Its enzyme cofactor function

The magnesium ATP complex

Owing to the magnesium ATP complex, magnesium acquires a decisive influence over metabolic reactions which use and supply energy. What is more, since the membrane-bound sodium-potassium pump is ATP-controlled, the electrolyte balance of all cells is dependent on magnesium.

There is nevertheless scarcely any outside influence on this intracellular effect, which is therefore not in the foreground of pharmacodynamic considerations.

The Second Effect Of Magnesium

Neutralization of negative charges

  The extracellular effect of chelation is, however, interesting: the bivalent, positive magnesium neutralizes negative charges on the outer side of the cells, thereby increasing the potential difference between the inner and outer side of the cell membrane.

  As a result, the excitation threshold (and therefore the resting potential) increases and the muscles are not so readily excitable.

  Pharmacological effects:

  In the heart, magnesium reduces arrhythmias.

  In skeletal muscle, cramps are less frequently triggered.

  In the uterus, premature contractions can be suppressed.

The Third Effect Of Magnesium

Calcium antagonism

The magnesium ion (Mg ²⁺ ) is larger, in its hydrated state, than the calcium ion (Ca²⁺ ) and is therefore capable of displacing the latter.

This calcium antagonism acts centrally on both muscle and nerve cells: the magnesium ion occupies the calcium binding sites on muscle cells, thereby displacing calcium into the calcium channel without undergoing the same migration itself.

Pharmacological effects:

  The blood vessels dilate.

  The oxygen balance of the cells is improved - on the one hand, via an increased supply and on the other hand via lower consumption.

The Fourth Effect Of Magnesium

Inhibition by Magnesium of the Release of Neurotransmitters

Inhibition of calcium - induced neurotransmitter release

Magnesium inhibits calcium - induced neurotransmitter release at the nerve cell level, or to be more precise, at the level of the presynaptic membranes of the sympathetic nervous system.

Pharmacological effect:

  The excitability of the nerve cells is diminished; among other things, adrenaline and noradrenaline release is reduced (important in heart disease and stress).

The Use Of Magnesium

Indications for magnesium

The area of application for magnesium has always been  derived from its pharmacology, the muscle and muscle cell:

  In cardiology, magnesium is administered in coronary heart disease and cardiac arrhythmias.

  In gynecology, magnesium is employed orally, in order to cover the increased requirements during pregnancy and lactation and as therapy for dysmenorrhea (cramp-like lower abdominal pain) and premature contractions.

  In eclampsia, (suddenly occurring life-threatening cramps during pregnancy, labour or child bed), parenteral administration is chosen.

  Neuromuscular disturbances throughout the whole body are grouped together under the name "tetanic syndrome." This includes, in addition to muscle contractions and gastrointestinal spasms, calf, foot and toe cramps. These are symptoms with which the patient often visits the physician and for which a high-dose magnesium preparation provides the ideal remedy.

  Migraine is also included in this area. In migraine, high - dose magnesium is employed as long - term prophylactic treatment: in a recent study, 600 mg of magnesium per day as magnesium citrate brought a significant reduction in the frequency of attacks (-41%) and the number of migraine days (-49%).

  In digestive problems, a side - effect of magnesium becomes a "virtue": at high doses, magnesium has a laxative effect. Pregnant women in particular therefore value magnesium as a mild, pain - free laxative.

CARDIOLOGY

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