This section is from the book "Materia Medica: Pharmacology: Therapeutics Prescription Writing For Students and Practitioners", by Walter A. Bastedo. Also available from Amazon: Materia Medica: Pharmacology: Therapeutics: Prescription Writing for Students and Practitioners.
(a) Constriction of the coronary arteries is a real digitalis effect, as shown by perfusion experiments. In the coronaries of young rabbits a solution of 1: 20,000 reduced the outflow from 8 c.c. per minute to 3 c.c. (Dixon), and by the ring and strip methods, Voegtlin and Macht showed contraction by both digitoxin and digitalin. From therapeutic amounts, this action is probably negligible, for, as Hatcher suggests, it seems improbable that the improvements in the circulation from digitalis could occur if the coronaries were constricted.
In acute poisoning, however, coronary constriction may be a factor in weakening the muscle; and in cumulative poisoning, it may be the cause of the muscular weakness which manifests itself by alternating weaker and stronger beats, the condition known as "pulsus alternans." This seems probable because the conditions in which pulsus alternans not due to digitalis is observed are those in which the coronary circulation is probably inadequate, viz., myocarditis with coronary sclerosis, the cardiac hypertrophy of nephritis, and paroxysmal tachycardia. (a) In coronary sclerosis the coronary blood-flow is retarded, (b) In hypertrophy a much larger blood-supply than usual is required, and a time may come when the coronary flow cannot meet the needs of the large mass of muscle. (c) In a rapid tachycardia the diastolic pause is much shortened, and, as the coronary circulation goes on essentially during diastole, this shortening obviously causes a serious interference with the cardiac blood-supply.
Pulsus alternans may, therefore, be a coronary effect, and when it results from digitalis, is a decidedly toxic one.
The increased pressure in the aorta invigorates the coronary circulation, and the prolonged diastasis from slowing allows it to last longer. At the same time the greater contraction in systole promotes the emptying of the coronary veins. The result is not only a greater supply of food and oxygen to the heart, to nourish it and permit of recuperation, but also a greater supply of the drug to the heart muscle to keep up its stimulation.
Hare (1897) has shown how digitalis can improve the heart nutrition in growing animals, and, as a result, probably the general nutrition. Of a litter of 10 pigs two months old, he kept 5 as a control, and treated the other 5 with normal liquid digitalis. The dose was 2 minims twice a day for a month. It was then gradually increased until, at the end of three months, it was 10 minims twice a day. The food was the same for all. There were no poisonous manifestations. After four and a half months the digitalis pigs averaged 4 pounds heavier than the others, and their hearts averaged heavier by more than 1/2 ounce (15 gm.). On examination by W. M. L. Coplin the ventricular walls were thicker, firmer, and more resistant on cutting, and their muscle-fibers measured 0.02 mm. wider (average), i. e., 1/10 to 1/5 larger than those of the control pigs.
Cloetta (1905) gave digitalis for several months to adult normal rabbits, without effect upon the size of the heart. Then he artificially produced aortic regurgitation, keeping some of the rabbits as controls, while to others he gave digitalis. The hearts of the treated animals were much more hypertrophied and more dilated than those of the controls, and were capable of much greater stimulation. Their aortas were also less dilated than those of the controls. These experiments would go to show that in growing animals and in hearts that required compensatory hypertrophy digitalis might improve the coronary circulation and the nutrition of the heart.
Electrocardiograms, as demonstrated by Cohn, Fraser and Jamieson, show a change under the action of digitalis (Fig. 22), and this effect has been observed to persist for from 5 to 22 days. It is not affected by atropine.
Digitalis may affect the heart in regard to its rate and rhythm; its tonicity, contractility, irritability, and conductivity; its nutrition, oxygenation, and recuperation. Through its action on the vagus it may produce loss of tonicity, slowing, phasic arhythmia, momentary standstill, or blocking of the auricular impulses in their passage to the ventricle. Through its action 12 on muscle it may increase the tonicity, the contractility, and the irritability, the last to a dangerous degree. It makes a specific change in the electrocardiogram.