Although we are unable, from the mere fact that the blood-pressure rises or falls after the administration of a drug, to say whether the result is due to the action of the drug on the heart or on the arterioles, yet we can come to some general conclusion regarding its mode of action by comparing the alterations which it has produced in the blood-pressure with those which occur in the pulse-rate. For in the normal condition of an animal, when all the nerves are intact, a rise in the blood-pressure renders the pulse slow by increasing the normal tone of the vagus centre in the medulla, and a fall of blood-pressure quickens the pulse by diminishing the tone. This mechanism tends in the normal animal to keep the blood-pressure more or less constant.

We find, therefore, that when alterations in blood-pressure and pulse-rate are depicted graphically, so that a rise in one curve indicates a rise in blood-pressure, and a rise in the other indicates quickening of the pulse, the two curves run in opposite directions if the alteration in blood-pressure is due to the arterioles, but they run parallel when the alteration is due to the heart (Fig. 87). Thus, if the vagi be cut, we find that the pulse-rate rises, and in consequence of this the blood-pressure also rises. Here the alteration in pressure is due to the heart, and the two curves are therefore parallel. If the vagi be irritated the pulse-rate falls, and in consequence of this the blood-pressure also falls. Here again the alteration is due to the heart, and the two curves are parallel.

Relation of Pulse rate and Arterioles to Blood pre 124

Fig. 87. - Diagram of a pulse and blood-pressure curve, where the alterations are due at first to the action of a drug on the heart, as in the case of atropine. The unbroken line indicates the blood-pressure, and the dotted line the pulse. After the injection shown by the vertical line the vagus is paralysed, the pulse becomes very rapid, and the blood-pressure rises. At A the vaso-motor centre becomes paralysed, the arterioles dilate, and the pressure falls. From a to b the action of the heart continues nearly uniform, notwithstanding the fall in blood-pressure, but at b the heart begins to become paralysed, and the pulse-rate and blood-pressure both continue to fall steadily till death.

Relation of Pulse rate and Arterioles to Blood pre 125

Fig. 88. - Diagram of pulse and blood-pressure curves, where the alterations are due at first to the action of a drug on the arterioles. The unbroken line indicates the blood-pressure, the dotted line indicates the pulse. The upright line indicates the time of injection of the poison. This is followed by contraction of the arterioles and consequent rise of blood-pressure. This rise stimulates the vagus roots, and causes slowness of the pulse. At b the vagus becomes paralysed, the pulse becomes quick, and the pressure rises still higher between a and B. At B the vasomotor centre becomes paralysed, the arterioles dilate, and the pressure falls, notwithstanding the rapidity of the pulse. At c the heart itself begins to be paralysed, its beats become slow, and both pulse and pressure fall steadily till death.

If, on the other hand, the arterioles are made to contract the pressure rises, but the increased pressure stimulates the vagus roots in the medulla and the pulse-rate falls, so that the curves run in opposite directions. If the arterioles dilate the pressure falls, and the vagus tone being lessened the pulse-rate rises; so the curves are again in opposite directions (Fig. 88).

An example of this is seen in the accompanying curve (Fig. 89), which illustrates the action of erythrophloeum - a substance similar in action to digitalis - on the circulation. After the injection of the drug the vessels contract, and the blood-pressure consequently rises and produces some slowness of the pulse. In a little while the vagus becomes paralysed, the pulse becomes quicker, and

Millims. of mercury.

Fig.89

Pulse in ten seconds.

Fig.89. - Curve of the pulse and blood-pressure in a cat after division of the spinal cord at the atlas and injection of erythrophloeum. (Prom a paper by Brunton and Pye, Phil. Trans. vol. 167.) the pressure rises still further. At a later stage the heart becomes slow, apparently from the action of the drug upon it, and the blood-pressure then falls again. At first then, where the alteration of pressure depends upon the state of the vessels, we have the two curves running in opposite directions, but when the alterations depend upon the condition of the heart we have them running parallel.1 It will be noticed that in the latter part of the curve, although the blood-pressure and the pulse sink together, they do not sink quite parallel; the pulse falling very rapidly and the blood-pressure very slowly. From this fact we may conclude that the arterioles are still contracted, and this affords an illustration of another way in which we judge of the effect of drugs upon the arterioles. This conclusion would not be warranted by the data contained in Fig. 89 alone. For the slowness with which the blood-pressure falls in this experiment might possibly be due to the heart beating more perfectly, at the same time that it begins to beat more slowly. An examination of the original tracings of the blood-pressure shows that this is not the case and that the beats of the heart became feeble at the same time that they became slow.

1 Although the rise in blood-pressure which accompanies that of the pulse is partly due to the heart, it is very probable that the contraction of the arterioles which caused the rise at first is not only continuing but increasing.

The mutual regulating power of the pulse and blood-pressure only exists when the vagi are working normally. If they should be paralysed, either by section or by the action of a drug, increased arterial pressure will no longer slow the pulse; it may even quicken it, and therefore the pulse-rate and blood-pressure may, in such a condition, run parallel even though the increased pressure should be dependent upon alterations in the arterioles.

But if the vagi are not paralysed, and we find on comparing the curves of blood-pressure and pulse-rate that they run parallel, a fall in the blood-pressure and slowness of pulse occurring together, or a rise in pressure and quickness of pulse accompanying each other, we may conclude that the alterations in such a case are due to changes in the action of the heart.

If, however, we find that the curves run in opposite directions, the pressure rising and the pulse falling, it is highly probable that the rise is due to contraction of the arterioles, and that the fall of the pulse is caused by the rise of pressure acting as a stimulus to the vagus roots. This is, however, not quite certain, as it might be due to the action of the drug upon the vagus, and the proper method of ascertaining this would be that employed by Ludwig, of allowing a quantity of blood to flow out into a bladder connected with a blood-vessel, so that the pressure should fall. If the pulse still continued slow in spite of the fall of pressure, it would be evident that the slowness was due to the action of the drug upon the vagus, and not to indirect action through the blood-pressure. By employing a bladder in this manner the blood can be quickly introduced again into the vessels after the effect of its withdrawal has been ascertained.

We not unfrequently find that, owing to the action of a drug the pulse, which has become slow during the rise of the blood-pressure, suddenly becomes very rapid notwithstanding that the pressure continues high. This is usually due to paralysis of the vagus-ends in the heart, and, when this occurs, the correctness of the conclusion which we draw from the occurrence may be ascertained by stimulating the vagus in the neck by a faradaic current, and seeing whether any slowing or stoppage of the heart occurs. Frequently we find that after the pulse has become quick from paralysis of the vagus, the pressure which the quick pulse had raised begins to fall again from paralysis of the arterioles. The pulse may continue quick and weak almost till death and then cease suddenly, or it may become gradually slow as well as weak from paralysis of the heart itself.