CORRELATION OF THE ELECTROPHYSIOLOGIC ACTION OF DIGOXIN WITH SERUM DIGOXIN CONCENTRATION

¹ Cardiovascular Research Laboratories, Department of Nutrition, Harvard School of Public Health; Levine Cardiac Unit, Cardiovascular Division, Department of Medicine, Peter, Beut, Brigham hospital; Cardiac Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts

Relationships between serum digoxin concentration (SDC) and drug-induced changes in cardiac automaticity were examined in dogs given single and multiple doses of this cardiac glycoside. Dominant serum half-time, measured by radioimmunoassay, was found to be 26.9 hours and rate of decline in SDC was not influenced by pre-existing body digoxin stores within the range studied. Changes in automaticity were assessed by 1) electrical provocation of repetitive ventricular responses (RVR) and 2) tolerance for acetyl strophanthidin (AS) infusion. RVR was demonstrable prior to the appearance of ventricular tachycardia (VT) provoked by digoxin. Post-VT RVR was observed when overt toxicity subsided. Initially, this post-VT RVR was manifest over a wide zone in electrical diastole. Reduction in the cardiac activity of digoxin was measurable from a narrowing in the post-VT RVR zone. Dissipation of digoxin action was also correlated with diminishing SDC; upon disappearance of VT, SDC was 12.7 ± 1.9 ng/ml (S.E.M.) and upon disappearance of 1) post-VT, RVR 7.65 ± 1.0 ng/ml. The effects of digoxin and AS upon cardiac automaticity were additive, and each drug comprised a fraction of the toxic (VT) digitalis dose. Over a range of SDC from 0 to 14 ng/ml, SDC was inversely correlated with AS tolerance. For each 1.0 ng/ml increase in SDC, a mean value of 5.2 µg/kg ± 0.65 less AS was needed to evoke VT.