Possible role of magnesium loss in the pathogenesis of myocardial fiber necrosis.

Cellular loss of Mg is associated with uncoupling of oxydative phosphorylation and disruption of Mg-dependent intra-mitochondrial enzyme systems. The link of Mg loss and its association with intracellular Ca accumulation in the pathogenesis of myocardial fiber necrosis (MFN) has been clearly established in dietary Mg deficiency. Rapid loss of myocardial Mg has been demonstrated also in acute hypoxic states and in patients succumbing to myocardial infarction. Evidence from this laboratory indicates that loss of myocardial Mg may be a basic biochemical denominator in the development of MFN of diverse etiology, initiating a stereotyped ionic disequilibrium which encompasses loss of inorg. P and K accumulation of Na and Ca. This applies to MFN elicited by NaH2PO4 loading of parathyroidectomized rats, by injection of cardiotoxic dosages of adrenergic amines or by ligation of coronary vessels. Prevention of myocardial Ca accumulation by prior parathyroidectomy, did not interefere with emergence of MFN nor did it obviate the Mg loss and the remaining electrolyte disturbances. These parallel findings with three unrelated models of MFN do not support the view of a determinant role of CA overload. Administration of Mg salts, on the other hand, provided substantial protection against MFN induced by NaH2PO4 loading of PTX rats or by isoproterenol. The protective effect was reflected in a highly significant shift of the deranged myocardial electrolyte pattern towards normal. In rats pretreated for 3 weeks with DCA-saline, isoproterenol induced myocardial electrolyte changes including Mg depletion were associated with an enormous potentiation of the arrhythmogenic propensity of this catecholamine, resulting in almost 20,000-fold increase in its acute toxicity. Pretreatment with Mg salts or Mg-sparing drugs offered clear-out protection against arrhythmias as well as against catecholamine-induced MFN.