Assay of digitalis glycosides in man

Abstract

The administration of digitalis glycosides is followed by a consistent and dose-dependent abbreviation of the duration of left ventricular ejection in normal individuals. The changes in left ventricular ejection time determined from the indirect carotid arterial tracing and corrected for heart rate (ejection time index) offer an easily derived measure of the myocardial response to digitalis. In the present studies, this effect of the cardiac glycosides was employed in comparing the temporal course of the action of four digitalis glycosides in man. Deslanoside (1.6 mg.) and ouabain (1.0 mg.) intravenously induced a temporally equivalent onset of action which reached a maximum 20 minutes after administration. Onset of the effect of digoxin (1.6 mg. intravenously) was similarly rapid. The initial response to digoxin was followed by a secondary delayed effect which reached its maximum six hours after drug administration. Digitoxin (1.6 mg. intravenously) evoked a slight initial effect followed by a slowly developing, late response which reached a maximum six hours after its administration. A logarithmic temporal dissipation of the effects of the digitalis glycosides on the ejection time index occurred. From the dissipation curves the physiologic half-lives of the glycosides were calculated: ouabain, 22 hour; digoxin, 33 hour; deslanoside, 36 hour; and digitoxin, 102 to 112 hour. When administered orally, digoxin elicited a response characterized by a late onset, delayed maximum and diminished potency when compared to the intravenously administered agent. The effects of digitoxin on the ejection time index were virtually identical by the intravenous and oral routes. The action of digitalis glycosides on ejection time index was demonstrated in patients with heart failure and in individuals with complete heart block. These effects on ejection time index offer a new, objective and quantitative approach to the measurement of the cardiac response to digitalis in man.