Effect of Various Digitalis Glycosides upon the Cardioinhibitory Action of Acetylcholine

We have previously reported that in the dog 10% of the lethal dose of a certain tincture of digitalis abolished the cardiac inhibition produced by acetylcholine. 1 A preliminary investigation to determine whether this was due to some one or other of the known glycosides in digitalis purpurea has not been conclusive, but indicates that the glycosides do not behave identically in respect to their modification of the response to acetylcholine. To test this question further, the 3 glycosides of digitalis lanata, Lanatoside A, Lanatoside B, and Lanatoside C were employed.∗

Anesthetized dogs were used. The minimal dose of acetylcholine bromide required to produce cardiac inhibition after injection into the femoral vein was determined. This varied in different animals from 0.1 to 1.0 mg. As the variation in an individual normal animal when tested at various intervals of time was occasionally as much as 50%, provision was made for such variation by using twice the minimal effective dose of acetylcholine. The cardio-inhibitory action of acetylcholine was determined from the carotid blood pressure tracing and by electrocardiograph tracings. An estimated 1/12th of the lethal dose of a glycoside was injected via the femoral vein, and similar doses were injected at 10-minute intervals until the animal died. Five minutes after each injection the test dose of acetylcholine (i. e. twice the original minimal cardio-inhibitory dose) was injected and observations made as to whether this did or did not cause cardiac inhibition. The results in 10 animals with each glycoside are shown in Table I.

Lanatoside C invariably abolished the cardiac inhibition produced by acetylcholine and did this when an average of 62% of the lethal dose was given. Lanatoside A produced such an effect in only 2 out of 10 experiments and Lanatoside B in but 5 out of 10 experiments.