EFFECT OF HEMODYNAMIC STATUS ON MYOCARDIAL DIGOXIN BINDING IN HYPOMAGNESEMIA

¹ Division of Cardiovascular Diseases and Internal Medicine, Department of Physiology and Biophysics and Department of Experimental and Anatomic Pathology, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

Because other investigators have reported enhanced toxicity of digitalis glycosides in magnesium-deficient states, we investigated the effect of acute depletion of serum magnesium on myocardial binding of digoxin-³H. Accordingly, 25 dogs underwent hemodialysis with the Kill artificial kidney; 16 were dialyzed against a standard physiologic solution and 9 against a magnesium-free solution. Serial determinations of cardiac output, systemic resistance, blood digoxin-³H and serum electrolytes were obtained. Under anesthesia, dogs were sacrificed one hour after injection of a standard dose of digoxin-³H (0.05 mg/kg), and radioactivity was measured by liquid scintillation in myocardial and subcellular fractions obtained by ultracentrifugation at 800, 8,000 and 105,000 x g. After dialysis the serum magnesium value (milligrams per 100 milliliters) was 2.13 (S.D. 0.25) in controls and 1.13 (S.D. 0.19) in magnesium-depleted dogs. There was no decrease in myocardial magnesium or change in other serum electrolytes. Regression analyses revealed positive correlations between blood and cardiac concentration of tritium and between cardiac radioactivity and mean systemic resistance, although a negative correlation existed between mean cardiac output and myocardial digoxin binding-³H. After adjustment for the independent variables of cardiac output and systemic resistance, no difference in digoxin-³H concentration was detected in blood, heart or subcellular fractions of mitochondria and sarcoplasmic reticulum between control and hypomagnesemic animals. This study suggests that acute reduction of serum magnesium does not affect myocardial binding of digoxin.