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Increase of the extracellular magnesium concentration reduces cardiac glycoside toxicity in the human myocardium

RH Schwinger, M Bohm, R Uhlmann, K La Rosee, A Koch and E Erdmann

Medizinische Klinik I, Universitat Munchen, Klinikum Grosshadern, Germany.

We studied the influence of magnesium on contractility and on force- frequency-relationship as well as on the positive inotropic and toxic effects of ouabain (OUA) on electrically driven human right auricular trabeculae. Radioligand binding experiments were performed with myocardial tissue from nonfailing and from terminally failing patients. Magnesium produced a concentration-dependent negative inotropic effect (P < .05). In contrast, OUA (0.03-0.1 mumol/l) concentration- dependently increased isometric force of contraction. The maximal positive inotropic effect of OUA (5.9 +/- 0.9 mN; 1 mmol/l of magnesium) was unchanged after increasing magnesium from 1 to 2 mmol/l (5.8 +/- 0.9 mN). OUA was as effective as Ca++ (15 mmol/l; 6.7 +/- 0.5 mN). OUA (0.05 and 0.03 mumol/l) exerted toxic effects after 2 hr and 0.08 or 0.1 mumol/l of OUA after 30 min, respectively. Time until toxic effects occurred after OUA (0.1 mumol/l) was significantly longer with 2 mmol/l of magnesium compared to 1 mmol/l of magnesium. In right auricular trabeculae, the force of contraction increased with increasing frequency (0.5-1 .5 Hz) of stimulation. The force-frequency- relationship becomes negative after elevation of extracellular Ca++ (2.4 mmol/l of Ca++) (2 Hz: 92 +/- 5.5% basal). Magnesium restored the force-frequency-relationship in the presence of enhanced Ca++ concentration (2.4 mmol/l of Ca++; 2 mmol/l of Mg++; 2 Hz: 145 +/- 16.9% basal). The receptor-density and affinity measured by [3H]OUA binding was not different in nonfailing and failing myocardium. Magnesium increased concentration-dependently the affinity of [3H]OUA to its receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 263, Issue 3, pp. 1352-1359, 12/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1992 by the American Society for Pharmacology and Experimental Therapeutics.