The activities of the heart depend upon a number of things, viz., the strength of contraction (contractility), the tone of the muscle, the recuperative power, the irritability, the conductivity of the stimulus from the pacemaker to the various chambers of the heart, or from one chamber to another, the rate of stimulus production, the rate of the beat, and the rhythm.

The heart's action may be affected by remedies directly or indirectly.

1. Directly, by action upon its muscle substance. If the muscle is stimulated, there is an increase in its tone, in its strength of contraction, and in its irritability; if the muscle is depressed, there are the opposite effects.

2. Indirectly, either through its nervous elements, through changes in its coronary circulation, or through changes in the peripheral resistance.

The nervous elements of pharmacologic importance are the accelerator and the vagus systems. The accelerators belong to the sympathetic nervous system. The center is presumed to have its seat somewhere in the brain, though it has not yet been clearly located. The fibers from this terminate about certain cells in the anterior horns of the upper portion of the spinal cord. These neurons in turn connect with the sympathetic ganglia, and the cells of these send fibers to terminate in the heart wall at the sinus node. The accelerator system, therefore, is composed of centers, nerves, ganglia, and nerve-endings. The effects of accelerator stimulation are those of direct muscular stimulation, as a rule. Rothberger and Winterberg (1910) have shown that stimulation of the left accelerator results in overaction of the left ventricle, and stimulation of the right accelerator in over-action of the right ventricle. But accelerator influence is not always certain, and at times accelerator stimulation will result merely in an increase in contractility without change of rate, or an increase of rate without change in contractility (Howell). The increase of rate is the result of shortened diastole.

The vagus system begins at the vagus center, a collection of cells on either side of the middle line in the medulla oblongata, and from here the nerve-fibers pass as the vagus nerves to groups of cells in the heart wall known as vagus ganglia. From the cells of these ganglia fibrils pass to the sinus node (the normal pacemaker) in the auricle, and to the auriculoventricular junctional tissues at the bundle of His. The vagus system comprises, therefore, the vagus centers, vagus nerves, vagus ganglia, and vagus nerve-endings. Its chief function, so far as the heart is concerned, is that of restraint or inhibition, and it is called the cardio-inhibitory nerve. Stimulation of any part of the vagus system results in slowing and weakening of the heart-beat, with depression of conductivity and loss of tone; while depression of the vagus system sets free the heart and results in increased frequency and strength of the beat and increased tone. The loss of tone is manifested by greater relaxation in diastole; the diminished contractility by less complete contraction in systole.. The slowing occurs essentially through a longer diastolic pause. Vagus stimulation and depression are very definite in their effects, and so great is the inhibitory action of the vagus that, under powerful stimulation, it can momentarily bring the heart to a complete standstill in a state of diastolic relaxation. Or excessive vagus action may have the effect of partially or completely checking the conduction of impulses from the auricle to the ventricle, with the production of heart-block. The vagus action, is primarily on the auricle, and, so far as known, is exerted upon, the ventricle only through the auriculoventricular bundle, except, perhaps, in a few cases in which the fibers of the right vagus pass directly to the ventricle (Cohn).

Robinson and Draper (1912), in electrocardiogram studies made during pressure of the human vagus in the neck, found that while pressure on either vagus slows the rate of contraction and retards conduction from auricle to ventricle, yet pressure on the right vagus has its predominating effect on the rate of the whole heart, while pressure on the left vagus predominates in interference with auriculoventricular conduction.

The vagi and accelerators are thus in some ways antagonistic, and as both are in a state of constant activity, they form a sensitive balanced control-mechanism which favors prompt response to any influence. (Compare with the antagonistic elements governing the size of the pupil.) The vagus and accelerator systems may be stimulated or depressed directly in any part of the system; or reflexly, through the center, by afferent impulses; coming from other parts of the body.

Resistance

Up to its limit of power, a heart will beat more slowly and more strongly in response to increased peripheral resistance; but if the resistance is beyond the cardiac power;, the result is weakness and dilatation and cardiac failure.