Another method of ascertaining the effect of drugs on the vessels is to measure the amount which flows out of them in a given time. This method may be employed either in the frog or in the higher animals. The method of employing it in the frog is to destroy the brain and spinal cord, and tie one cannula into the heart or aortic bulb, and another into the inferior vena cava. The aortic cannula is connected with a reservoir containing saline solution, or defibrinated blood, which can be made to pass into the aorta and circulate through the vessels at any desired pressure by simply raising or lowering the reservoir; the fluid flows out through the cannula in the vena cava, and the quantity is registered upon a revolving cylinder.

By this method Cash and I have found that potassium chloride, contrary to our expectation, causes great contraction of the vessels; that barium and calcium and strontium do so also, but to a less extent. The instrument used for this purpose consists of a light lever, one end of which is depressed each time that a drop falls upon it. An electric circuit is thus broken, and the fall of each drop is readily recorded by means of an electromagnetic marker; at the same time the pressure under which the circulation is going on is also recorded by means of a manometer. Slowing of the flow indicates of course contraction of the vessels, and acceleration indicates dilatation of the vessels.

The general results of our experiments with several metallic salts are shown in the accompanying table. Most of the drugs experimented on cause contraction of the blood-vessels, but we are unable at present to arrange them in the exact order of their strength of action.

Lithium causes slight contraction.

Potassium (very dilute solutions) causes dilatation. Ditto (solutions of 1/4000) causes contraction.

Barium causes rapid contraction.

Calcium „ gradual „

Strontium ,, gradual „

Magnesium „ slight ,,

Aluminium (much diluted) has no effect. 1 per cent, needed to produce any effect.

Iron causes slow contraction.

Copper „ powerful „

Zinc „ „ „

Tin „ „ „

Cadmium „ slight „

Nickel „ „ „

Cobalt ,, ,, „

Platinum „ powerful „ but none is produced by solutions weaker than __1

In experiments made by such methods as that just described we reduce the problem of the action of drugs on the blood-vessels to a very simple form, although we have still to distinguish whether the drug acts directly on the contractile walls of the blood-vessel or on the nervous elements contained in them. There is at present no means of absolutely separating those two factors, but it is probable that the nerves die sooner than the muscular fibres, and that if the experiments are carried on for some time the effect of the drug is chiefly, if not entirely, exerted upon the muscular fibres. This is probably the explanation of the different effects of chloral on the vessels of the kidney observed by Ludwig and Mosso (p. 283).

In experiments on the flow of blood through the vessels of warm-blooded animals, the circulation is kept up in much the same way as in the frog. The blood may be used cold, or may be kept at the temperature of the body. The cannula is usually inserted either into the artery supplying an organ such as the kidney, or supplying a single muscle, or it may be put into the descending aorta, so that the blood passes through the whole of both lower extremities. The flow is measured by the rate at which the blood issues from the corresponding vein.

This method we owe to Ludwig, who, along with his pupil Mosso, made a number of experiments on the circulation through the kidney. The conclusions arrived at were : - that venous blood causes contraction, and oxygenated blood, dilatation of the vessels; but the dilatation which richly oxygenated blood, circulating after venous blood, causes in the vessels is only temporary, and they soon return to their normal calibre. Mosso's experiments have been repeated by Severini, who used the lung instead of the kidneys. He finds that the alternate circulation of oxygenated and of venous blood acts in the manner described by Mosso, but that when oxygenated blood is passed through steadily the vessels contract and the flow through them is diminished; venous blood, on the contrary, when circulated for a length of time causes the vessels to dilate and the flow through them to increase. The action of venous blood upon the arterioles appears indeed to be similar to its action upon other tissues. A small or moderate quantity of carbonic acid acts as a stimulus and causes contraction, but great interference with the natural process of oxidation produces paralysis.

Nicotine, in the proportion of 1 in 10,000, causes contraction of the vessels; but this is also temporary. One per cent., on the contrary, immediately causes dilatation.

Atropine has a very powerful action; but this differs completely according to the dose. One part in 100,000 causes temporary contraction of the vessels, which soon passes off. One in 10,000 causes contraction, which, instead of returning simply to the normal, passes into dilatation, and then returns to the normal. One in 5,000 has a similar action, but instead of the dilatation passing away, and the vessels returning to their normal size, the dilatation persists, and the kidney soon dies.

Chloral causes the vessels to contract and then to dilate; but besides this it has a peculiar action, either increasing rhythmical contraction and dilatation of the vessels, when such movements are already present, or inducing them when they are absent. It only acts upon the vessels when the blood contains oxygen; and when the blood is saturated with carbonic acid, it has no action on them at all. Its action is also altered by the condition of the kidney. When this organ has been kept for twenty-four hours in a cool place, its vessels still retain their irritability; but small doses of chloral, instead of causing contraction followed by dilatation, only produce contraction, and a much larger dose is required to produce dilatation. This alteration is due to a change in the vessels - either in their muscular walls, or more probably in the ends of the vaso-motor nerves - and not to any change in the blood; for it occurs when serum instead of blood is passed through the kidneys. When the kidney is dead, chloral mixed with the blood, instead of increasing the rapidity of the current as in the living organ, or leaving it unaltered, as one would expect, greatly diminishes it. Chloral also alters the effect of artificial stimulation of the kidney. Faradaic currents or induction-shocks do not seem to affect the normal vessels, but constant currents cause dilatation, which continues while the currents are passing and diminishes after they cease. When chloral is added to the circulating blood, however, the vessels contract during the passage of the current instead of dilating, and dilate slightly after the current has ceased. When the chloral has acted so far upon the vessels as to dilate them greatly, the constant current causes no alteration while it is passing, but, after it ceases, dilatation increases still further.