Magnesium deficiency in the pathogenesis of cardiac arrhythmias has recently been accepted. This is exemplified in the latest Advanced Cardiac Life Support protocol for the treatment of torsades de pointes. In experimental models, magnesium deficiency results in a number of electrocardiographic alterations, as well as changes in automaticity and conduction. Among the electrocardiographic changes are prolonged PR interval and QT interval, premature atrial complexes, atrial tachycardia, and fibrillation. Ventricular premature complexes and tachycardia have also been noted, in addition to ventricular fibrillation and torsades de pointes.
Magnesium is a crucial cofactor in the sodium-potassium-ATPase enzyme system, which contributes to the sodium and potassium flux across cell membranes. This flux in turn determines the potential needed for depolarization of cardiac muscle. Of note, digitalis blocks the sodium-potassium-ATPase enzyme system; it has been shown in the dog model that hypomagnesemia facilitated digitalis-toxic arrhythmias and that most of these arrhythmias were terminated with intravenous magnesium sulfate.
Iseri et al showed that ventricular arrhythmias recalcitrant to antiarrhythmics (lidocaine or beryllium) or to potassium supplementation responded to magnesium used as a therapeutic agent. This response occurred even in the presence of normal serum magnesium levels.
In several of the cases mentioned, the arrhythmia appeared to be that of torsades de pointes, and studies have indeed shown therapeutic confirmation in the abolition of this arrhythmia by bolus infusion of magnesium.
Magnesium's effect as it pertains to acute myocardial infarction has been difficult to interpret, especially with respect to mortality rate differences. This has occurred because of nebulous reporting of concomitant use of therapy with ß-blockers, aspirin, or antiarrhythmics and different lengths of observations.
Schecter et al concluded that the cardioprotective effect of magnesium was more of a general myocardial protective effect than one solely due to reduction of arrhythmias. They postulated that among the possible mechanisms included were coronary vasodilatation, reduction of the catecholamine effect in myocardial tissue, and calcium-magnesium interactions at the cellular level preventing ischemic deposition of calcium in cardiac mitochondria.
The LIMIT-2 study of 1992 was the first large-scale randomized placebo-controlled trial to show a decrease in total mortality of the magnesium-treated group; this effect reached statistical significance. The second large-scale trial to study survival after myocardial infarction in patients given magnesium infusion was the ISIS-4 trial. The ISIS-4 study showed no survival benefit from the addition of intravenous magnesium. In a recent review of these contradictory results, Hennekens et al stated, "Nonetheless, the data suggesting that early magnesium therapy reduces reperfusion-related injury have led to the hypothesis that the longer time between the start of myocardial reperfusion and the achievement of therapeutic serum magnesium concentrations may account for the null finding in ISIS-4."
The use of parenteral magnesium as a therapeutic modality in the treatment of preeclampsia is time honored. The proposed mechanism of action relates to magnesium acting as a calcium antagonist either at the membrane level or intracellularly. Although magnesium-induced reduction in vascular tone is partially explained by altered calcium flux, it may also produce this effect by altering the prostaglandin system. Watson et al showed that magnesium facilitated release of potent vasodilatory prostaglandin in a dose-dependent manner. They suggested that increased prostaglandin is the explanation for magnesium's therapeutic effect in preeclampsia.
The utility of magnesium as a therapeutic modality in the treatment of asthma has been alluded to for decades. Two studies have shown that magnesium infusions increased the forced expiratory volume in 1 second (FEV1), though the mechanism of action on the respiratory tree remains to be elucidated. One proposed mechanism is smooth muscle relaxation at the bronchial level. This is similar to the effect exerted by magnesium on vascular smooth muscle by means of its influence on calcium channels.
South Med J. 2001;94(12) © 2001 Lippincott Williams & Wilkins
Cite this: Magnesium: Its Proven and Potential Clinical Significance - Medscape - Dec 01, 2001.