Influence of decreased and increased magnesium supply on the cardiotoxic effects of epinephrine in rats.

Female Sprague-Dawley rats kept on a standard chow or on a magnesium (Mg)-deficient diet during 6 days received s.c. injections of 0, 25, 50, 100 and 200 micrograms of epinephrine (Ep). 1 h before, they were orally treated with 0, 125 or 250 mg of Mg/kg b.w. given as magnesium aspartate hydrochloride. Drug-induced changes were studied by analyzing serum and cardiac tissue samples (Mg, Ca, K, Na and in addition glucose, FFA, cholesterol and creatine kinase in serum) taken at 7 different times (15 to 420 min) after treatment with Ep; effects were evaluated by considering the respective areas under the concentration-time curves (AUC). AUCs were calculated with linear and logarithmic graduation of the time-scale and were also transformed into logarithms. In additional experiments, animals of both diet groups were treated with Mg and Ep as described above and the hearts, excised after 420 min, were prepared for histological examination. Cardiotoxic effects induced by adrenergic overstimulation were aggravated by Mg deficiency. Most pronounced electrolyte alterations and histologically detectable cardiac necroses were observed in the Mg-deficient animals at 420 min following the s. c. injection of 200 micrograms of Ep. On the other hand, oral Mg treatment induced hypermagnesemia and reduced toxic effects of Ep--especially Ca overload of the heart muscle--in controls and in Mg-deficient rats.