The Onset and Magnitude of the Contractile Response to Commonly Used Digitalis Glycosides in Normal Subjects

Abstract

Controversy exists over the rapidity of onset of the inotropic effect of various digitalis glycosides. Shortening of the systolic time intervals (STI) provides a quantitative measure of the inotropic effect of digitalis glycosides in human subjects. Total electromechanical systole corrected for heart rate (QS₂I) is the most sensitive of the STI since it combines the shortening effect of digitalis glycosides on both the pre-ejection period and ejection time. Normal volunteer subjects were studied serially following i.v. injection of 1.6 mg cedilanid-D (C) (n = 18), 1.0 mg ouabain (O) (n = 12), 1.6 mg digoxin (D) (n = 16), and 1.6 mg digitoxin (DT) (n = 9). The shortening of QS₂I was corrected for the molecular weight of the digitalis glycoside. The onset of shortening of the QS₂I/ mole proved to be exponential for each digitalis glycoside. This allowed estimation of the maximum shortening of QS₂I/mole (A) which would occur assuming zero excretion, from which the time constant (t_c) of the curves could be determined. There was no significant difference in A among the digitalis glycosides. The t_c, were 5.8 min (O), 7.2 min (C), 23 min (D), and 56 min (DT). These t_c were significantly different except for O and C. Thus both C and O have a rapid onset of activity which is significantly shorter than either D or DT. The t_c for C in patients with congestive heart failure is the same as normals. This study provides a heretofore unavailable, accurate measure of the differences among commonly used glycosides.