Myocardial fiber necrosis due to intracellular Ca overload-a new principle in cardiac pathophysiology
Fleckenstein, A.; Janke, J.; Döring, H.J.; Leder, O.
Recent Advances in Studies on Cardiac Structure and Metabolism 4: 563-580
1974
ISSN/ISBN: 0363-5872 PMID: 4468468 Document Number: 5531
Ca ions are highly cardiotoxic if their influx into the myocardial fibers becomes abundant. The intracellular Ca overload initiates a deleterious high-energy phosphate deficiency by excessive activation of Cα-dependent intracellular ATPases and by impairing the phosphorylating capacity of mitochondria. This Cα-induced high-energy phosphate exhaustion is a crucial point in the etiology of the myocardial fiber necroses produced in rats by large doses of 13-adrenergic catecholamines, particularly isoproterenol, or by a number of other cardiotoxic agents. Accordingly, the myocardium is sensitized to necrotization by factors which favor Ca overload (dihydrotachysterol, 9α-fluorocortisol acetate, NaH, PO,, high extracellular Ca, alkalization). Conversely, the structural integrity of the hearts can be protected by any substance or procedure which prevents an excessive intracellular Ca accumulation, such as inhibitors of transmembrane Ca influx, e.g., Verapamil, D 600, prenylamine; K and Mg salts; low extracellular Ca due to thyrocalcitonin or EDTA treatment; or acidification by CO, respiration or oral NH4 Cl administration.
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