I. Subjective Manifestations: a. Loss of appetite, nausea, vomiting, diarrhea.

b. Oppression about heart, palpitation, tachycardia, consciousness of premature or skipped beats.

c. Headache.

II. Objective Manifestations: a. Effect on sinus node - 1. Excessive slowing.

2. Sinus arhythmia c. Effect on muscle - Overexcitability

Exaggerated respiratory. Non-respiratory.

b. Effect on a-v bundle or Toward's node

Prolonged auriculoventricular in-terval (incipient block). Partial or complete block (with or without bradycardia).

Nodal rhythm.

1. Premature beats (extrasystoles).

2. Paroxysmal tachycardia.

3. Nodal and retrograde rhythms. 4. Auricular flutter.

5. Auricular fibrillation.

6. Ventricular fibrillation.

d. Combined effects on a-v bundle and on muscle -

1. In auricular fibrillation

1. Complete heart-block, but little or no bradycardia.

2. Coupled rhythm.

3. Phasic arhythmia.

2. In normal rhythm - complete block without bradycardia (owing to increased excitability). e. Constriction of coronary arteries - a possible influence pulsus alternans. These have all been explained in detail above.

In this connection the possibility of persistence of effect must be kept in mind, for, as ascertained by Hatcher in cats, the drug action may continue in some cases for as much as three weeks or a month after a single intravenous dose. I have observed persistence of partial heart-block for three and one-half weeks after the stoppage of digitalis, and of complete block for at least one week. Conn's electrocardiographic tracings have shown a digitalis effect in man as late as twenty-two days after the drug was stopped. Cushny reports a case of auricular fibrillation in which, through the influence of digitalis, "inhibition had gained a permanent control over the heart," so that the effect persisted indefinitely after the drug was stopped, or was perpetuated by an occasional dose. From my clinical experience I should judge that such an effect in auricular fibrillation is not uncommon.

Except when it is administered intravenously, the margin of safety with digitalis is a large one, so that there is no undue danger in the use of even large doses by mouth or hypodermatically, if the administration is stopped when one of the following conditions arises, viz.:

1. Nausea becomes marked.

2. The radial pulse goes below 60. The pulse may become progressively slower for a few days after the drug is stopped, hence the necessity for ceasing its administration before the slowing has become extreme. 3. A rapid ventricle with rate unaffected by digitalis for several days suddenly becomes slower (heart-block).

4. A regular ventricular rhythm changes to irregular, as from premature beats or the development of auricular fibrillation; or becomes intermittent, as from partial heart-block.

5. Paroxysmal tachycardia occurs.

6. The absolutely irregular rhythm of auricular fibrillation becomes slow and regular (complete heart-block), or shows coupled rhythm or phasic arhythmia.

A considerable risk may be avoided by refraining from the use of digitalis - (a) When the ventricle is intermitting; (b) when there are premature beats; or (c) when there is bradycardia.

Clinical reports of fatalities have borne out Hatcher's findings that an intravenous dose of any one of the principles of the group is much more active if digitalis has previously been administered by mouth or hypodermatically. For, as Hatcher reports, even as late as a month after the intravenous injection in a cat of a nearly fatal dose of digitalis, the test animal may require a smaller intravenous dose for lethal effect than an animal that has had no digitalis.

Treatment

In the simplest condition of poisoning, when excessive slowing or irregularity or intermittence of the heart, or tachycardia, begins to show, the treatment is simply to stop the drug and keep the patient quiet in bed until the effect of the drug has worn off. To check excessive vagus action, atropine sulphate, 1/65 grain (0.001 gm.), may be employed hypodermatic-ally, but its effect lasts not over an hour. For excessive irritability, sodium bromide, 1 to 2 drams (4-8 gm.), morphine sulphate, 1/4 grain (0.015 gm.), and a hot-water bag or ice-bag over the heart may give some relief. In severe poisoning there must be absolute repose and freedom from exertion for several days, the mere effort of sitting up in bed being sufficient in some cases to precipitate failure of the circulation and death. If necessary, body warmth must be maintained by blankets, hot-water bottles, etc. Symptoms are treated as they arise, there being no specific treatment.

So far as conduction is concerned, there is some evidence that caffeine tends to antagonize digitalis, hence it may prove a good drug in heart-block. On several occasions I have seen caffeine apparently undo the work of digitalis in auricular fibrillation, an observation confirmed by Barton.

Therapeutics

From our studies, it is evident that the only use for digitalis in therapeutics is to modify the action of the heart. And it is to be employed neither to constrict the arteries nor to act directly upon the kidneys. It is also evident that among the cardiac disturbances which require treatment there are those in which digitalis has a great value, those in which it has a small value, those in which it has no value at all, and those in which it is distinctly harmful or even dangerous. Discrimination, therefore, is most essential in the use of this powerful remedy.

We learn further that the determining factor in our choice of digitalis as the drug to use is not the state of the valves, but rather the functional condition of the various parts of the cardiac mechanism. According to Lewis, the relative frequency of disorders of the cardiac mechanism in hospital cases would approximate as follows: Heart-block, 5 per cent.; sinus arhythmia, 5 per cent.; pulsus alternans, 5 per cent.; paroxysmal tachycardia including auricular flutter, 10 per cent.; premature contractions, 34 per cent.; auricular fibrillation, 41 per cent. The role of digitalis in these several conditions is as follows: