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SUMMARYThe mechanism by which magnesium affects digitalis-induced arrhythmias was studied in dogs with and without beta-receptor blockade. Digoxin was infused at a rate of 2.5,ug/kg/min until ventricular tachycardia developed, then half the animals were given MgSO4, the other half saline. In animals given MgSO4, sinus rhythm was immediately re-established; in animals given saline, ventricular tachycardia persisted. In animals with beta-receptor blockade, MgSO4 was as effective in abolishing ventricular tachycardia as in those without beta-receptor blockade. We found no evidence that magnesium re-activated digoxin-inhibited (Na+, K+)-ATPase, altered myocardial or microsomal digoxin binding, or acted via the autonomic nervous system. Magnesium's direct effect on calcium and potassium fluxes across the myocardial cell membrane may be the mechanism of its antiarrhythmic action in digitalis-toxic arrhythmias.MAGNESIUM has been shown to be effective in the treatment of cardiac arrhythmias brought on by digitalis in man and experimental animals.1-4 The mechanism by which magnesium affects digitalistoxic arrhythmias has not been clearly demonstrated. Seller and coworkers3' 5 suggested that magnesium reverses digitalis-induced inhibition of membranebound sodium, potassium, adenosine triphosphatase (Na+, K+ )-ATPase, thought to be the " digitalis receptor" involved in both the arrhythmogenic and inotropic effects of digitalis.6`9 Magnesium-deficiency is associated with increased myocardial digoxin uptake;10 hypermagnesemia might, therefore, decrease digitalis uptake by the heart. Magnesium decreases potassium efflux and intracellular calcium"' and might thereby offset the toxicity of digitalis. In addition, by interfering with the effects of calcium, magnesium causes autonomic blockade12 which might influence digitalis-toxic arrhythmias.The present investigation was, therefore, designed to determine magnesium's mechanism of action in arrhythmias induced by digitalis toxicity. Our studies demonstrate no evidence of magnesium reactivation of digoxin-inhibited (Nal, K+)-ATPase, or displacement of digoxin from the heart, or of change in

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The effect of digoxin, at two different inotropic levels, was examined in normo- and hyperkalaemic dogs. For similar inotropic responses, normo- and hyperkalaemic dogs had similar levels of (Na+, K+)-ATPase inhibition and microsomal-bound digoxin.