Interactions of magnesium and potassium in the pathogenesis of cardiovascular disease

The interactions of Mg and K in cardiovascular disease are diverse and complex. However, Mg deficiency and loss from the heart and arteries, caused e.g. by dietary deficiency or imbalance, or by diseases and their treatment, can contribute to cardiovascular damage, and to functional abnormalities. Although Mg deficiency interferes with K retention, it is seldom measured in routine clinical practice, and the need to correct low Mg levels, in order to replete K, is rarely considered. The heart, with its high metabolic activity, is particularly vulnerable to Mg deficiency or loss because of the importance of Mg in mitochondrial structure and enzymatic function. The need for Mg to activate Na/K ATPase has long been known. Mg has also been shown to be structurally part of the enzyme in cardiac mitochondria. Additionally, Na/K exchange occurs in association with phosphorylation and dephosphorylation, reactions that are also Mg-dependent. The demonstration that Mg modulates K+/proton (H+) exchange, and that cation selectivity in Na+ and K+ exchange for H+ is highly dependent on the concentration of Mg++, provides new insights into how Mg protects against K loss. The loss of myocardial K that results from Mg deficiency contributes to electrophysiologic changes, as can the Ca shifts of Mg loss. A high Ca/Mg ratio also predisposes to arterial spasms, and increases catecholamine release. Thus the arrhythmogenic potential of Mg deficiency can be related to imbalances between Mg and K or between Mg and Ca, or both. Electrical or K-induced catecholamine release is increased by a low Mg/Ca ratio, as are increased fatty acids and lipids and intravascular hypercoagulability. K or Ca loading of the patient with undiagnosed Mg inadequacy is not only often unsuccessful, but it may carry inherent risks. It can intensify the Mg depletion, the arterial contractility, and ECG abnormality. In the patient receiving digitalis, Mg deficiency can increase drug toxicity. In the case of myocardial infarction, Mg deficiency can increase the risk of malignant ventricular arrhythmias and sudden cardiac death. In the absence of alcoholism or gastrointestinal disease, the use of loop diuretic therapy for congestive heart failure, especially in elderly patients, is the most common cause of Mg depletion. A high concurrence of hypomagnesemia with hypokalemia, from whatever cause, has been documented. However, systemic Mg deficiency can exist despite normal Mg serum levels. Methodological difficulties hamper direct detection of cellular Mg deficiency, but patients can be indirectly evaluated by use of Mg-loading tests, which may be of combined diagnostic and therapeutic value.(ABSTRACT TRUNCATED AT 400 WORDS)