This section is from the book "Materia Medica Pharmacy, Pharmacology And Therapeutics", by W. Hale White. Also available from Amazon: Materia Medica Pharmacy, Pharmacology And Therapeutics..
The heart is capable of spontaneously originating impulses which in health begin in the sinus venosus, and spread downwards over the auricle and the ventricle to the apex. It used to be considered that these movements were due to spontaneous impulses proceeding from the cardiac ganglia surrounding chiefly the entrance of the superior and inferior venae cavae, the entrance of the pulmonary veins, and the auriculo-ventricular groove; but we now know that there is no certain evidence that these ganglia originate impulses, and most of the evidence goes to show that the contraction of the muscular fibres is due to spontaneous impulses arising in them. This contractile power of the muscular fibres can be inhibited by the vagus, the fibres of which proceed from the vagal nucleus in the medulla, and can be augmented by the augmentor or accelerator nerve-fibres, which proceed downwards in the cervical spinal cord to the upper dorsal nerves, from which they pass through the first thoracic ganglion to the sympathetic, and so to the cardiac plexus, and thence to the heart. We are ignorant of any function for the cardiac ganglia; we know that medullated nerve-fibres lose their medulla in them, and that more fibres proceed from them than enter them. Possibly they have a nutritive function. We have, therefore, only to consider the action of drugs on the muscular substance of the heart, on the vagal or inhibitory fibres, on the vagal centre, on the augmentor, accelerator, or sympathetic fibres, and on the accelerator centre. The centres are remarkably easily affected by afferent impulses, proceeding from the heart itself or from almost any part of the body. Our information concerning the action of drugs on the heart of man is necessarily rather inexact, for many experiments are difficult to perform upon the mammalian heart, consequently the cold-blooded animals have been largely used; and as some differences are observed among them - for example, between the fiog and the tortoise - it is probable that the deductions drawn from experiments upon the hearts of warmblooded animals are not wholly applicable to man. In the following account of drugs the action described is that of a moderate dose; the action of a large dose is generally the reverse of that of a moderate dose.
A. Drugs acting upon the Heart directly. - Our knowledge of these has been gained by studying the action of drugs upon excised hearts or pieces of the heart, and the action of drugs locally applied to the heart, either by gently applying a solution externally, or by means of a transfusion cannula. It is difficult to decide whether a drug acts upon the muscular fibre itself, or upon the fine nerves between these fibres, so that no attempt will here be made to distinguish between these actions. As the apex of the heart contains fewer nerves than the rest of the organ, it has been concluded that if a drug acts upon the apex, when it is cut off from the remainder of the heart, it acts upon the muscle only; but it would be difficult absolutely to deny the existence of fine nerve-fibres in the apex. The vagus or inhibitory nervous mechanism has been much more studied than the accelerating. The effect of stimulating the muscle may be either to increase the rate or the force of the beat, or to do both; that of stimulating the minute branches of the vagus or its terminations in the heart will be either to diminish the rate or the force of the beat, or both; and the effect of stimulating the accelerator fibres will be just the opposite; and in each of these cases the effect of paralyzing will be the reverse of stimulating. The distinction between a stimulating effect on the terminations of the vagus and a depressing effect on the terminations of the accelerator nerves might be determined by observing the effect of stimulation of each of these nerves before and after the local application of the drug, provided that it has been shown that the muscle itself is not affected by the drug; but this is often difficult to prove. It is easily seen that the complexity of the problem is so great that it will be most convenient to classify the drugs which act locally on the heart by the effect they produce, without attempting to say whether they act on the muscle or nerve terminations.
Drugs increasing the force of the contraction:
(3) Sparteine. (4; Squill. (5) Saponin.
In large doses these drugs in frogs always cause arrest of heart in systole; in mammals the final arrest may be in diastole with some, e.g., digitalis. They all slow the pulse.
(11) Dilute solutions of salts of the alkaline metals.
(12) Dilute solutions of copper double salts.
These drugs have the same action without the final arrest in systole. The rate of the pulse is not markedly altered.
Drugs the chief action of which is to decrease the force of the contraction, usually with stoppage in diastole:
(1) Diluted acids.
(2) Strong solutions of salts of the alkaline metals. (3) " of barium salts.
(4) " of copper double salts.
(5) " of zinc double salts.
(6) Strong solutions of chloral.
(7) Muscarine. (8) Pilocarpine. (9) Sapdhin (large doses).
(12) Salicylic acid (large doses).
Drugs an important action of which is to increase the rate of the cardial beat:
Drugs an important action of which is to slow the rate of the cardiac beat (see also first list given above):
Drugs which increase both the force and the number of the beats:
(1) Ammonium salts.
(7) Arsenical salts.
Drugs which decrease both the force and the number of the beats:
(1) Antimony salts.
(3) Hydrocyanic acid.
(5) Veratrum Viride.
B. Drugs acting on the Vagus Centre. - If we observe that the giving of a drug to an animal alters the beat of the heart, but that this alteration can be done away with, either by cutting the vagi or stimulating the peripheral end of the nerve, - if one only of them be cut, - we may conclude that the drug acted on the vagus centre in the medulla.
Drugs which stimulate the vagus centre: that is to say, the pulse is slowed, but this slowing disappears on section of the vagi:
(2) Chloral hydrate.
(5) Veratrum Viride.
(11) Convallaria Majalis.
(12) Hydrocyanic acid.
(13) Cocaine (large doses).
(14) Staphisagria (Delphinine.)
Only very early in their action.
(18) Increased blood-pressure.
(19) Venous blood.
Drugs which depress the vagus centre: Large doses of the drugs mentioned in the last list, and drugs which diminish the blood-pressure, such as amyl nitrite nitroglycerin, and the nitrites.
C. Drugs acting on the Accelerating Centre. - We do not know anything of drugs which depress this. Probably some stimulate it, for their administration renders the pulse still more rapid after the vagi have been cut.
They are -
(5) Delphinine. (6) Any drugs which make the blood venous.
The drugs most used for their action on the heart are digitalis, strophanthus, ammonium salts, sparteine, squill, convallaria majalis, caffeine, alcohol, ether, chloroform, cactus, strychnine, belladonna, aconite, antimony, and hydrocyanic acid. The therapeutic indication for each of these drugs will be found given under the individual drug.