The effect of certain drugs upon the still-stand produced by irritation of the vagus or of the venous sinus is very remarkable. A large number of drugs, more especially atropine, curare, coniine, and nicotine, when injected into the circulation have the power of completely destroying the inhibitory power of the vagi as far as the rate of rhythm is concerned, so that when their fibres are stimulated the heart is not arrested, nor are its beats rendered slower, but they are, on the contrary, quickened.

These poisons again may be divided into two classes: Class I. containing atropine and its congeners. Class II. containing curare, coniine, nicotine, etc.

These two classes agree in destroying the inhibitory power of the vagus nerve, so that irritation of its trunk will no longer produce still-stand or slowing of the heart. They differ in their action on the still-stand produced by irritation of the venous sinus. Atropine and its allies prevent any inhibition occurring when the venous sinus is stimulated, or when muscarine is applied to the heart directly. This action affects chiefly the rhythm of the heart, for muscarine can still reduce the force of the cardiac contractions after the application of atropine.

Poisons of the second class do not prevent the still-stand of the heart occurring on irritation of the sinus, nor do they prevent muscarine from arresting the beats of the heart. This antagonism of atropine and muscarine has hitherto been explained on the supposition that muscarine greatly stimulates inhibitory centres in the sinus or auricle, while atropine paralyses them.

These two classes also agree in leaving unaffected the accelerating nerves of the heart.1

These complicated effects are very hard to explain on the ordinary hypothesis.

It is still more strange that although atropine and muscarine have such apparently opposite effects, they both agree in ultimately paralysing the inhibitory function of the vagus.

Muscarine, as I have already mentioned, arrests the movements of the heart; but, if the circulation be carried on, this arrest is only temporary, and is succeeded by a period, first of slowness, then of irregularity, and then of return to the normal; the stage of irritation of the inhibitory centre by the muscarine gradually passing into that of complete paralysis. During the time when the pulse is still slow in consequence of the action of muscarine, irritation of the vagus itself has no power to arrest it, or even to increase the slowness, while at that very time irritation of the accelerating nerves quickens its pulsations just as it would those of a normal heart.2 When the accelerating nerves are thus irritated, there is often not only an increase in the number but also in the size of the pulsations, very much as Gaskell has observed under other conditions from irritation of the vagus in the frog. This action is only to be observed in moderate conditions of poisoning. When the poisoning is very profound, irritation of the accelerating nerves has a very peculiar effect, sometimes producing so-called staircases, and sometimes a prolonged condition of still-stand, half in systole and half in diastole.

1 In the frog the accelerating nerves appear to run along with the inhibitory fibres in the vagus trunk. In warm-blooded animals these fibres run in separate nerves which pass out from the spinal cord along the vertebral artery and reach the heart through the sympathetic system. Although the chief accelerating fibres pass in these nerves, some are also contained in the vagus trunk, both in warmblooded animals and in frogs. In animals poisoned by atropine, irritation of the vagus usually produces acceleration of the pulse.

2Weinzweig. From experiments in Von Basch's laboratory. Archiv f. Anat. u. Phys., Phys. Abt., 1882, p. 527.

A marked difference is seen between the action of the accelerating nerves and the inhibitory fibres of the vagus, as the inhibitory action follows very shortly after the irritation of the vagus, and usually ceases very shortly after the irritation is removed, whereas that of the accelerating nerves does not occur until some time after the irritation has been applied, and often lasts a good while after the irritation has been removed. The two sets of fibres also appear to influence a different period of the heart's action, the inhibitory affecting the pause or relaxation, while the accelerating affect the systole or contraction. This condition renders it not improbable that we may have to do here with an action of these nerves on two different parts of the heart - the ganglia and the cardiac muscle.

It is quite clear that, in order to get any satisfactory explanation of these phenomena, we must take into consideration not only the rhythmical actions going on in the cardiac ganglia and those in the cardiac muscle separately, but also the relation to one another of these rhythms both as regards their energy and rate.