In order to explain the effects of various poisons upon the heart, a hypothetical view of its nervous system has been proposed by Professor Schmiedeberg,1 and I have endeavoured to represent this in the accompanying diagram (Fig. 106) .2 It consists of a ganglion, m, which keeps up a rhythmical contraction of those muscular fibres of the heart to which it is connected by the fine nervous filaments, e. This ganglion is connected by an intermediate apparatus with an inhibitory ganglion, I, which can retard or stop the muscular contractions which m produces; and by another apparatus, c, with another ganglion, q, which quickens the contractions, I is connected by an intermediate apparatus, a with the retarding fibres, v, of the vagus, and d with the quickening nerve, s, of the heart.

This schema has been adopted by Professor Harnack.3 It has been supposed that motor ganglia are present because the apex of the heart of the frog, which contains no ganglia, will not contract rhythmically if left entirely to itself, whereas the ventricle containing ganglia will do so.1

1 Schmiedeberg, Ludwig's Arbeiten, 1870, p. 41.

2 ' Experimental Investigations of the Action of Medicines,' Lauder Brunton, British Medical Journal, December 16, 1871.

3 Pharmakologische Thatsachen fur die Physiologie des Froschherzens, Halle, 1881.

It has been supposed that inhibitory ganglia are present, because when a little muscarine is applied to the heart it causes it to stop in diastole. This effect is not developed all at once, but goes on gradually increasing, and its action in this respect seems rather to point to its effect upon ganglia than upon nerve fibres.

Fig. 106.   Diagram of the hypothetical nervous apparatus in the heart. M, motor ganglion. I, inhibitory ganglion. Q, quickening ganglion. v, inhibitory fibres ; and s, quickening fibres from the head.

Fig. 106. - Diagram of the hypothetical nervous apparatus in the heart. M, motor ganglion. I, inhibitory ganglion. Q, quickening ganglion. v, inhibitory fibres ; and s, quickening fibres from the head. A, a', b, and c, intermediate apparatus. e, fibres passing from the motor ganglia, m, to the muscular substance, p. [For simplicity's sake only one set of motor ganglia has been represented, but other similar ones are supposed to be present in other parts of the heart, and so connected with this set that they all work in unison. It must be remembered that this diagram is purely hypothetical : but if this be carefully borne in mind, the sketch will be found of service in remembering and comparing the action of different poisons on the heart.]

It has been supposed that the vagus acts through this inhibitory ganglion or ganglia because irritation of the vagus arrests the heart in diastole, just as muscarine does; but it has been supposed to be connected by some intermediate apparatus with the inhibitory ganglia, because we find that when nicotine is applied to the heart irritation of the vagus will no longer arrest its beats, but that irritation of the venous sinus, in which the inhibitory ganglia have been supposed to be situated, will do so at once.

It has been supposed that the inhibitory apparatus, I, was connected by an intermediate structure with the motor ganglia, m, because physostigmine does not produce the extraordinary still-stand which muscarine does, but it counteracts to a certain extent the effects of atropine which muscarine does not. Physostigmine in small doses increases the excitability of the vagus, so that a slight stimulus applied to that nerve, so slight that it would under ordinary circumstances be insufficient to affect the heart, will stop it.2 In large doses it appears to paralyse the vagus. The difference of action between muscarine and physostigmine seemed to show that they acted on different nerve structures; while the mutual power of atropine and physostigmine to neutralise each other's effects within certain limits indicated that atropine acted on the same nerve structure as physostigmine and consequently on a different one from muscarine.1

1 The recent researches of Gaskell have shown that the muscular fibre of the heart of the tortoise will contract, although it contains no ganglia. The question of muscular rhythm independent of ganglia will be considered further on.

2 Arnstein and Sustschinsky, Wurzburger physiol. Untersuch. iii.

When atropine is applied to the heart it completely removes the effect of muscarine and totally prevents any arrest being produced either by irritation of the vagus or the venous sinus. It has therefore been supposed that nicotine acts upon the intermediate apparatus, a, but that atropine acts either upon I or upon b.

The reason why it has been supposed that quickening ganglia exist is, that when irritation is applied to the vagus after its inhibitory power has been destroyed by the administration of nicotine or atropine it no longer produces slowness or still-stand of the heart, but, on the contrary, quickens its pulsations. But the quickening does not take place immediately, it only occurs some time after the application of the stimulus. If it is applied only for a short time, no quickening may take place until after its removal, but the quickening once induced remains for a considerable time. This seems to indicate that the stimulus does not act through nerve-fibres, as these would conduct the stimulus directly to the muscle, but rather through some ganglionic apparatus. It has been supposed that this apparatus is not identical with the motor ganglia themselves, because if the heart is irritated directly, its pulsations at once become quickened, and the quickening does not last long after the irritation is removed.

It is evident, however, that though this hypothetical schema allows us to explain in a fairly satisfactory manner the action of many drugs, yet it can only be looked upon in the same light as the hypothesis of cycles and epicycles in astronomy, which was useful for a time, and enabled astronomers not only to recollect but to predict facts. Its use was only temporary, and the hypothesis just at the time of its greatest complication gave place to one of the greatest simplicity.

It is probable, indeed almost certain, that the same thing will occur in regard to the action of drugs upon the heart, and that the whole complication of motor ganglia, inhibitory ganglia, accelerating ganglia, vagus endings, and intermediate fibres, may resolve themselves simply into a question of the mutual relationships between the rate of rhythm and rapidity of conduction in the muscular fibres, nervous ganglia, and nerve-fibres respectively. Schmiedeberg's hypothetical schema has been most useful for several years, but facts which it will not explain are beginning to accumulate, and we must look in another direction for their explanation. The whole question of the action of drugs upon the heart is far from being completely solved,

1 Lauder Brunton, op. cit.

but I shall try, if possible, to indicate the direction in which pharmacology is at present looking for an explanation.

For this purpose it will be necessary to go still more fully into the physiology of the heart than we have already done.

Before doing so, however, it may be advantageous to put in a tabular form the action of the most important drugs on the various parts of the circulatory apparatus, according to the prevalent opinions at present.1

Theories regarding the Mode of Action of Drugs upo 146

Fig. 107. - Diagram of the heart and vessels to illustrate the action of drugs on the various parts of the circulatory apparatus as given in the following tables. A, indicates accelerating ganglia.

1 In drawing up this table [see pp. 316-319] I have been greatly aided by the admirable paper of Professor Boehm, read before the International Congress in London in 1881.