A detailed study of the effect of vagus stimulation on the heart has shown that it affects all the four fundamental properties of the heart muscle (fig. i 1). By inhibiting the S-A node, it depresses the rhythmicity ; by affecting the conductive system, it retards the propagation of the impulse in the auricular muscle and in the A-V bundle ; by affecting the muscle proper, it diminishes its con tractility and each beat becomes weaker, in consequence of which the refractory period of the heart is shortened; and finally it di minishes the irritability of the heart. Whether the vagus has a direct action on the mammalian ventricle is still doubtful.
If both vagi are cut, the heart immediately begins to beat faster, showing that under normal conditions a continuous stream of impulses passes down the cardio-inhibitory nerves, which do not allow the heart to beat at its full independent rate.
For obvious reasons, section of the vagi cannot be performed in man, but we have at our disposal a drug which paralyses the peripheral nerve endings of the postganglionic vagal fibres, namely atropine, an alkaloid obtained from belladonna.
The question as to what controls the normal tone of the vagi has been the subject of many researches, and at present we know of several factors that are concerned. Amongst them we must mention first the blood pressure. Marey was the first to show that, other conditions being equal, the vagus tone increases with increase in the blood pressure. This effect is probably not due to the direct stimulation of the vagus centre in the medulla, but to stimulation by high blood pressure of special sensory endings in the aorta, in the ventricles, and in some of the blood vessels going to the brain. The sensory impulses reflexly retard the heart by stimula tion of the vagus centre. Changes in the composition of the blood and various drugs may also affect the vagus centre. Asphyxia, and the action of morphine may be mentioned as such centrally acting stimuli; they retard the heart, but only if the vagi are intact. Reflexes from various sensory nerves may stimulate or inhibit the vagus centre ; for instance, inflation of the lungs diminishes vagus tone (the Hering Breuer reflex) ; increase in the output of the heart has the same effect (Bainbridge reflex). Stimulation of the respiratory passages, as in the case of inhalation of an irritant volatile substance, retards the heart, and high intracranial pres sure has the same effect. There are also stimuli which may excite the peripheral nerve endings of the vagi in the heart itself, i.e.,
substances which will act even after section of the vagi, but not after injection of atropine—for instance bile salts, which enter the general circulation in the case of jaundice.
The intimate mechanism by means of which the vagus produces its effect on the heart has been a field of intense experimentation and theorisation. It has been suggested that the vagus impulses produce "interference" waves with the impulses originating in the S-A node ; that the vagus is a nerve which abolishes the kata bolism or disintegration processes associated with activity, and leads to anabolism or reconstruction processes; that on account of similarity in the effect of stimulation of the vagus with that of potassium salts, the vagus possibly liberates free potassium from a colloidal combination or from an adsorbed state from the pro teins. According to Loewi, the vagus acts by producing some chemical substance (of the choline type) which is the active factor.
His experiments support thetheory most brilliantly. If a per fused frog's heart is stopped by stimulation of the vagus, and if the perfusion fluid is collected from the heart and transferred to a beating frog's heart, the second heart will show all the effects of vagus stimulation. The chemical substance responsible has been extracted and dried, but has not yet been obtained in a sufficiently pure form to establish its chemical nature.