All natural
cardiac glycosides (CG) have a
hydroxyl (
OH) group attached to
carbon 14 (C 14) of the
steroid nucleus which has been considered important for their pharmacological action. To investigate the relation between chemical structure and
biological activity of CG, we studied the cardiac effects of a semisynthetic derivative if gluco-
digitoxigenin that lacks the C 14
hydroxyl group; the compound was named
Dig-3 and corresponds to the number of a series of semisynthetic
glycosides being studied. On the failing heart of the Starling's heart-lung preparation
Dig-3 reverts experimental
cardiac failure. Electrophysiological experiments in anesthetized dogs (
morphine chloralose) have shown that
Dig-3 shortens the functional refractory period of the ordinary atrial myocardium (OAM), and lengthens that of the specialized atrial tissue (SAT). The basal excitability is reduced in both tissues, however OAM is more susceptible to
Dig-3 action. The conduction velocity of impulses in SAT diminishes 50% with one tenth of the lethal dose (LD) of
Dig-3 whereas in the OAM, an equivalent decrease is achieved with 60% of LD.
A-V dissociation induced by the infusion of toxic doses of
Dig-3 reverted to sinus rhythm in about 6 min after the administration was stopped. We conclude that the presence of the
OH group attached to C 14 of digitalis molecule does not constitute a structural requirement for the preservation of its inotropic and electrophysiological actions on the heart, although its potency is greatly diminished.