[Clinico-electrophysiologic effects of magnesium, especially in supraventricular tachycardia]

Clinical electrophysiological effects of magnesium (Mg2+) are known for more than 60 years. Mg2+ is a cation to be found ubiquitously in the human body and is involved in more than 300 different enzymatic reactions. However, so far this ion has not been established as a standard therapeutic tool for the treatment of supraventricular tachyarrhythmia. This may be explained by the inconsistent efficacy of Mg2+, partly in relationship to a given plasma Mg(2+)-concentration, partly caused by the uncertainty regarding the dosage and injection rate or the unawareness of the clinical effects of the cation. Mg2+ influences myocardial metabolism by its effects on contractility and electrical activity. Both effects are closely linked. About 12% of cardiac Mg2+ is found in the mitochondria and 2 to 3% in the myofibrils. A large portion is incorporated in adenosin mono-, di- and triphosphate. Mg2+ affects intracellular calcium by inhibiting the influx of calcium into the myocyte through sarcolemmal channels, by modulation of cyclic AMP and by competing with calcium for binding to a single high affinity site on actin. Mg2+ has been linked to a naturally occurring calcium channel blocker. Furthermore Mg2+ blocks the outward current through some potassium channels resulting in an inward rectification of these channels. This suggests that internal magnesium functions as a potassium channel-blocking agent. Early afterdepolarizations are oscillations in the membrane potential and lead to triggered activity and therefore are the electrophysiological substrate of "torsade de pointes" type of ventricular flutter. Mg2+ is able to inhibit both early afterdepolarizations and tachyarrhythmias. Additionally Mg2+ interferes with the sodium-potassium-ATPase system by stabilizing the transmembrane gradient of both cations. Mg2+ deficiency alters this balance and leads to increased neuromuscular excitability. Digitalis is able to block the sodium-potassium-ATPase system, which can be cancelled by Mg2+. Thus the first clinical reports of the therapeutic use of Mg2+ refer to digitalis-induced atrial arrhythmia and ventricular ectopy which could be converted to sinus-rhythm or suppressed by the intravenous application of Mg2+ in 1935. Some years later, the first successful termination of paroxysmal supraventricular and ventricular tachycardia following application of 1.5 to 3 g of Mg2+ was published. But only in the late eighties, systematic studies of the electrophysiological effects of Mg2+ were performed and clinical use was first tested in random fashion in the nineties. Summarizing studies in older patients with different heart diseases and young healthy volunteers the most pronounced and clinically important effect seems to be related to the modulation of the AV node function. The prolongation of the PR interval by 7 to 12% without changing significantly heart rate, QRS duration and QT duration, can be considered a consistent and reproducible effect of Mg2+. In electrophysiological studies a prolongation of the AH interval by 8 to 18%, of the Wenckebach cycle length by up to 20% and of the refractory period of the AV node by 6 to 20% is usually observed, but no change of the retrograde conduction, or the HV interval can be found. Furthermore sinus node recovery time increases by 10% and sinuatrial conduction time by up to 25%. There is no significant effect on intraventricular conduction and atrial and ventricular refractory period. Additionally no significant effect on the anterograde and retrograde refractory period of accessory pathways could be measured; however in some cases (up to 40%) an anterograde block in the accessory pathway may be observed after intravenous Mg(2+)-injection. For the treatment of paroxysmal atrioventricular tachycardia like AV-nodal reentrant tachycardia or orthodromic atrioventricular reentrant tachycardia in WPW syndrome, Mg2+ has been applied in a limited number of recent prospective but uncontrolled studies. Recently, an