Besides its effect upon the structures of the heart, digitalis in the laboratory may produce another effect on the circulatory organs, viz., contraction of the peripheral arteries. The evidence of this is: If a loop of dog's intestine in situ is inclosed in an oncometer so that any change in its volume can be measured, the administration of a laboratory dose of digitalis is seen to be followed by shrinkage in the volume of the intestine. The shrinkage is synchronous with a heightened general arterial pressure, and is due to contraction of the vessels. If the splanchnic nerves are cut so as to remove connection with the centers, the shrinkage is less than before, therefore stimulation of the vasoconstrictor center is an effect of the drug.

Fig. 22.

Fig. 22. - A. The solid line represents the normal outline of the electrocardiogram. The T wave is directed upward. The dotted line shows the change which occurs in the T wave under the influence of digitalis. B, in a similar way, shows the change in certain cases when the T wave is initially directed downward. Under the influence of digitalis it turns upward (A. E. Cohn, Journal of Experimental Medicine, June, 1915).

Further, in perfusion of an isolated loop of intestine or of a severed leg, i. e., of organs removed from connection with the nerve-centers, if digitalis is added to the perfusing fluid, the venous outflow is decreased. This effect is due to thecontrac-tion of the arterioles, and shows that there is a peripheral vasoconstrictor effect. The peripheral effect may be analyzed -

(a) by the use of apocodeine or ergotoxine, two drugs which paralyze vasoconstrictor nerve-endings; the digitalis still causes contraction, so must directly stimulate the arterial muscle; and

(b) by perfusion of a coronary or pulmonary artery; these contract under digitalis, though they have no vasoconstrictor nerves. There is a slight stimulation of the vasoconstrictor nerve-endings, but the main peripheral effect of digitalis is exerted on the arterial muscle. Thus digitalis causes contraction of the arteries by stimulating the arterial muscle and the vasoconstrictor center, and slightly by stimulating the vasoconstrictor nerve-endings.

The contraction of the arteries occurs mainly in the splanchnic area, but ordinarily occurs also in the vessels of the limbs. After powerful doses the arteries of the limbs, as shown by the plethysmograph, may be dilated; for they have less power of contraction than the splanchnics and may be forced into dilatation when the blood is prevented from entering the splanchnic area (for it must go somewhere). The increased peripheral resistance in itself is a resistance stimulus to the heart, and, in addition, promotes the coronary circulation during the diastolic pause. Richards and Wood report an increased production of epinephrine after digitoxin or strophanthin. Stewart and Scott report that in three cases of auricular fibrillation the blood-flow in the hands was promptly and decidedly increased by digitalis, this being doubtless a cardiac effect. In one case with normal rhythm the blood-flow in the hands was slightly reduced.

These are the effects from laboratory doses, i. e., poisonous amounts administered intravenously, and they show the tendency of the drug. But in practical therapeutics the effect is not so striking. In fact, it is the consensus of opinion among students of the circulation that in medicinal doses digitalis does not cause constriction of the arteries in measurable degree.

Arterial Pressure

In laboratory animals digitalis results in increased output of blood from the heart, increased peripheral resistance, and an increased quantity of blood in the arteries at the expense of that in the veins. Hence we have a decided rise in'arterial pressure.

In man the smallness of the dose and the slowness of the drug action permit the sensitive blood-pressure control mechanisms to adjust themselves; hence digitalis in therapeutic amounts may cause no rise in arterial pressure. As Mackenzie expresses it, "contrary to expectation the blood-pressure is raised only in exceptional cases, even when the drug is repeatedly pushed until full physiologic action is apparent, and even when the patient is evidently much benefited by the drug." Price, Lawrence, and others note similar absence of pressor changes.

In our own experience, a certain number of heart cases have shown decided improvement in arterial pressure while taking digitalis; indeed, in a few cases there has been a very close relation between the amount of the drug being taken and the systolic pressure. But many other cases have shown no effect at all upon the pressure, though the appearance of poisonous symptoms demonstrated that full dosage was being given.

We have, therefore, reached the same conclusion as a number of other students of the circulation, viz., that frequently the improvement in the circulation under digitalis cannot be fully judged by estimation of the arterial pressure. In auricular fibrillation arterial pressure records are worthless, as no two beats are alike.