This remedy, like Convallaria, comes to us from Russia, and, like many of our best remedies, was first used by the common people as a remedy in dropsy and heart disease. Experiments were first made by Dr. Botken, the results of which were described by Dr. Butnon in a graduating thesis. The experiments made on both cold-blooded and warm-blooded animals with different preparations of Adonis (infusion and both aqueous and alcoholic extracts) showed that its action is to stimulate both the inhibitory apparatus and motor ganglia of the heart, to increase the contractility of the cardiac muscle, and to cause the contraction of small arteries in different parts of the organism without affecting the vaso-motor centre.
Under its influence in cases of dropsy the cardiac contractions increase in force, the pulse become less frequent, more regular and full, the urinary secretion increases from 200 to 2,000 or 3,000 cubic centimetres, and albumen and casts disappear from the urine.
In cases where the dropsy was due to a disturbance in the compensation and activity of the heart this remedy acted very satisfactorily. The heart-beat increases in force, and the size of the heart rapidly diminishes; the heart-sounds and murmurs, especially the presystolic and systolic in stenosis, are more marked and distinct. The heart-rhythm is more regular and somewhat slower; therefore the pulse is slower, and in most cases the pulse-wave fuller and slower. The urine increases from 300 to 3,000 cubic centimetres, a tenfold increase of the watery element. All deposits disappear, the specific gravity diminishes, and the urine has a very pale color. There is an absolute increase of the chlorides and urates, the body weight diminishes, and the oedema decreases rapidly; the dimensions of the liver increase, cyanosis and dyspnoea disappear, and respiration becomes full and regular.
In the largest number of cases great relief was experienced at the end of the first day. Complaints were less frequent, and in the course of a few days disappeared entirely.
These clinical results were obtained in hospital practice, where the cases were closely and carefully watched.
It is indicated in cases of (a) endocarditis, with valvulitis, when the heart-muscles are endeavoring to overcome the valvular obstruction and need the aid of specific remedies to increase the tonicity of those
14 tissues; or (b) when there is impending or actual dilatation of the heart from a giving way of muscular fibres. This condition is marked by diminished force of the heart’s action, with lowered blood-pressure everywhere, especially in the kidneys, decreasing their functional activity.
It has been found equally potent in secondary heart disease, following Bright’s disease, when we find a diminished action of the heart, pulse irregular or intermitting, passive venous stasis, dropsy, etc. A typical case from these hospital records is as follows: A common laborer, with chronic valvular disease, with dilatation. After the use of Adonis the heart diminished in size, the congestion of the lungs, well marked, almost disappeared, the oedema of the legs and the ascites disappeared entirely, palpitation of the heart and dyspnoea diminished so much that the patient was discharged from the hospital and returned to work.
The dose of Adonis, when given in infusion (13 of the herb to 123 of water), is a tablespoonful every two hours in severe cases; in chronic cases every four hours. Of the fluid extract the dose is one to two minims, or increasing from 5 to 10 drops.
By the above it is seen that Adonis is quite similar, if not identical, in its action on the heart to Digitalis and Convallaria. The symptomatic differences have not yet been brought out by any physiological provings. We can resort to it when, as is often the case, the two medicines above named fail to act favorably, or cease to give the patient relief. It is said to be more liable (than Digitalis) to cause gastro-intestinal irritation, nausea, vomiting and diarrhoea, in large doses.
In experiments made on frogs, in both the isolated heart and the heart in situ, diastole ends the scene. Two questions now arise, namely: What is the cause of this stoppage in diastole, and what produces the slowing of the cardiac rate occurring in the heart when lying in its sac?
The diastolic arrest of the isolated heart can only be due to one of two things – either the inhibitory cardiac apparatus is stimulated, or the heart-muscle and its motor ganglia are depressed. The latter seems far more likely, not only from analogy, but from the fact that in the experiments performed on the non-eviscerated heart of frogs the inhibitory nervous apparatus was found to be stimulated centrally and not peripherally; and, furthermore, the very character of the slowing of the isolated heart showed it to be due to stimulation, but to increasing depression.
That the vagi are not stimulated peripherally by this drug at any time was proved by the following experiments, and also by the results of the observations on the action of the drug upon dogs, which will be described farther on.
If the inhibitory nerves be cut before the Adonidin is placed in the pericardial sac, the usual increase in rate under such circumstances takes place, and the addition of a small quantity of the drug now immediately increases the rate still further, without the appearance of any primary stage of slowing of rate. This proves that the primary slowing occurring when the vagi are intact must be due to exaltation of their function, and also proves that the drug must directly stimulate the heart-muscle; for the rapid rate under these circumstances is not one of weakness, but of power. It should not be forgotten that this drug in large quantities finally stops the heart in diastole, whether the vagi are intact or divided. In small quantities it does not produce the primary slowing of the pulse, nor does it bring on the peculiarly weak and imperfect movements which have already been described as occurring before death. In other words, it requires large doses to affect the pneumogastric, and large doses to depress the heart-muscle.
One more point is to be decided. Is the rapid stage following the primary slow stage in the viscus in situ due to paralysis of vagi, to direct stimulation of the heart which overcomes inhibition, or to both? While I am unable to state whether overstimulation takes place, it is a fact that the pneumogastric nerves are certainly in this second stage depressed by the drug, for galvanization of these nerve-trunks during this stage failed to produce as marked a slowing of rate as should have occurred, provided the inhibitory pathway was open. From this point we may conclude that although the stimulation of inhibition in the first stage is centric, the paresis of inhibition in the second stage is peripheral.
The same changes are present when the drug is injected into the posterior lymph-sac of a frog. The animal soon becomes passive and immovable, and dies shortly so quietly that its death is not noted until he is handled. That the high arterial pressure produced by this drug is due in part to centric stimulation of the vaso-motor system is proved by the fact that the mesenteric bloodvessels are seen to dilate after section of the spinal cord.
Further evidence of this fact was adduced when studying the influence of the glucoside on the circulation of mammals; for there is but little, if any, difference in the action of Adonidin on the dog and frog. The injection of the quarter of a grain of Adonidin into the jugular vein of a dog, weighing twenty-five pounds, causes a great increase of cardiac force and arterial pressure and a marked decrease in pulse-rate. Following this stage of exaltation of force and pressure come a marked fall of arterial tension and, as is usual, a decrease of pulse-force, with an increase of pulse-rate. This condition remains the same for some time, until at last the heart beats irregularly, and stops in diastole, just as did the heart of the lower animals. We have, therefore, several stages to be accounted for in the action of this drug in the dig, viz., the increase in arterial pressure, in cardiac force, and decrease in pulse-rate in the first stage; the fall of arterial pressure and force and increase of pulse-rate in the second stage, and the arrest of the heart in diastole at the end of the third stage. Turning attention to the rise in arterial pressure, the writer eliminated all danger of a rise due to asphyxia by curarizing the dog, artificial respiration being maintained. Under these circumstances arterial pressure was increased as greatly as when the animal was not curarized. What, then, is the cause for this rise in arterial pressure? Probably two factors lie at the bottom of this condition, namely, centric vaso-motor stimulation, aided by increased cardiac force; for when the spinal cord was divided high up in the cervical region, thereby producing vaso-motor palsy, the rise in pressure under the influence of Adonidin was of course less marked, and the rise which did occur must have been due to increased cardiac force. The experiment on the fourth dog was made to discover how the slowing of the pulse was produced in the first stage. One-fourth grain of the drug was administered in the same manner as before, the animal having first been curarized. No sooner was the slowing of the heart-beat most marked than the vagi were divided, and instantly the pulse was increased from 102 to 192 per minute, proving that the slowing was due to stimulation of inhibition, and that this stimulation was centric. The increase in force has already been shown to be due to a direct stimulant action of the drug on the heart itself. In regard to the symptoms of the second stage, we find that the fall of arterial pressure is due to palsy of the vaso-motor system, since, when the cord is intact, galvanization of the sciatic nerve or asphyxia did not bring about increased pressure.
The decrease in pulse-force is due to the depressing action of the drug on the heart itself, as is also the arrest in diastole. The increase in pulse-rate is due to inhibitory failure; for in the dog, as well as in the frog, galvanization of the vagi failed to slow the heart. In the next experiment the dose of the drug used was much smaller than before, since it had become evident that the larger doses were absolutely toxic in their character. An eighth of a grain was, therefore, injected into the dog’s jugular vein, curare and artificial respiration being used. As a result, I found that in small doses this glucoside does not cause any primary slowing of the heart, but increases its frequency, its force and the arterial pressure from the first, all three of these features being permanent and constant under the smaller dose. Even with this dose, however, the animal died. A twelfth of a grain given slowly to a large dog did not produce death nor a primary slowing in rate, but seemed to increase the rate, force and pressure. In this last experiment no tracing was taken, the jugular vein only being exposed. I should have stated before that when I poisoned a small dog by a large dose of Adonidin there were symptoms of nausea and intestinal spasm, accompanied by the expulsion of faeces. The animal had no convulsions or spasms, but lay on its side, with pupils widely dilated, and, when death occurred, respiration continued some moments after the heart stopped. The same writer thinks that Convallaria and Caffeine possess higher diuretic powers and less cardiac influence than Adonidin.
Finally, he sums up the results of his observations as follows:
In doses of 1/3 gr. Adonidin –
1. Increases arterial tension.
2. Regulates the heart-beat.
3. Diminishes the frequency of the pulse.
4. Increases the force of the cardiac contractions.
5. Acts with rapidity, its effects being only present during its administration.
6. Increases diuresis.
7. Is well tolerated.
8. That the indications for its use are the same as for Digitalis.
OTHER EXPERIMENTS WITH ADONIDIN.
Huchard presented, in the Societe de Therapeutique, at a meeting held on December 23rd, 1885, a series of cardiographic and sphygmo-graphic tracings taken from patients under treatment with adonidin (vide Gaz. Hebd., January 1st, 1886). Our readers will recall that Adonidin is the glucoside of Adonis vernalis, and was first extracted by Cervello as an amorphous yellowish extract of a bitter taste. The first experiments with the drug were made by Lesage and Montague. The cardiac frequency was found under its influence to be decreased, and at the same time a peculiar state of ventricular rigidity is induced, the ventricle itself becoming pale and anaemic.
Huchard injected 2 to 2 cg. (15/100 to 3/10 gr.) hypodermically into rabbits, and found respiration reduced, the cardiac force raised, disappearance of paralytic symptoms, fall of temperature, and death ensuing after fifteen to twenty hours. In man the infusion of Adonis vernalis may be given in 4 to 8 grammes (1 to 2 dr.) for a dose, four times daily, or, still better in pill form, 4 to 5 daily, 1/10 of a grain each. Huchard reported several cases in which Adonidin had been successful. In one case of interstitial nephritis, with galloping heart-sounds, anasarca and beginning asystole, in which Sparteine had been given in vain, Adonidin induced a profuse diuresis and an unquestionable improvement in the patient’s condition. For some time, however, the drug had to be discontinued, on account of the diarrhoea and vomiting it produced. When the quantity of urine fell off again, the remedy was again exhibited, and again relieved the most urgent symptoms. The diuresis rose two to four quarts daily. At the same time the arterial pressure grew stronger, the pulse more regular and full, and the oedema and cardiac frequency receded. In a woman having a mitral affection, but no heart-murmur, the drug produced a very audible systolic murmur. In typhoid fever, where great reduction of the arterial pressure exists, Huchard thinks the drug might be used advantageously to raise the pressure.
This plant has been examined by Italian doctors as to its therapeutic value, and Albertoni reports in its favor. His experiments were made on animals and sick and healthy people. In cases of insufficiency of heart action, with feeble, irregular, rapid pulse, diminished arterial pressure, dyspnoea and diminished excretion of urine, the administration of the plant in substance produced in a few days the return of normal pulse, increase of the pressure of the blood, and disappearance of the respiratory oppression. The quantity of urine increased from eight hundred to three thousand cubic centimetres in a day.
These good results were not obtained in cases in which the organs susceptible to the influence of Adonis, such as the kidney epithelium, muscular fibre and the nerve apparatus of the heart, had already retrograded to too great an extent.
The dose is 4 to 8 grains a day, given in substance or infusion. The effects manifest themselves about the third day.
Neither of these species of Adonis has been proved in our school. There were some attempts to prove Adonis vernalis, but the results were very meagre. It seems to cause irritation of the bladder, strangury, etc., but all cardiac medicines do that.
BARIUM AND ITS SALTS.
Barium has not yet been used as a remedy in cardiac affections, but it has a decided action on the heart and capillary vessels.
The provings already show this, and also show that, like Digitalis, its primary action is to stimulate the cardiac muscle, and, secondarily, to depress its vitality. The symptoms in a fatal case of poisoning by Baryta acet., reported by Dr. Dartmoor, are: “Pulse 125 to 130, very small and frequent. Pulse 65. Pulse 56, and even as low as 25. Irregular pulse.”
Baryta carb. has : “Violent, long-lasting palpitation. Palpitation when lying on left side. Palpitation renewed when she thinks of it. Pulse full and hard.”
Baryta mur. has : “Beating of the heart very irregular. Pulse scarcely perceptible. Pulse rapid. Pulse soft and irregular.”
Brunton, in his experiments, found Barium to act as energetically as Veratrine. He classes it with Digitalis, Helleborine, Nerein, Scillin, Strophanthus, Caffeine, etc.
Hahnemann says the Baryta salts are useful in the maladies of old age. The condition of the heart and bloodvessels of the old is certainly similar to what we might expect the secondary symptoms of Baryta to be. I shall not be surprised if we find in Baryta the remedy for many cardiac disorders which accompany old age. In senile or fatty degeneration it may rival Digitalis or Strophanthus.
The following statement of its action on the heart and circulation is certainly worthy our study:
SIMILARITY OF BARIUM TO DIGITALIS.
“The salts of Barium, though they have been occasionally employed therapeutically, have never been very generally recognized as really useful therapeutic agents, either in this country or abroad, partly perhaps from a want of knowledge as to their effects both in physiological and pathological conditions. This knowledge Dr. A. Bary, of Dorpat, has recently endeavored to supply, to some extent at least, by making a large number of investigations on the action of the Barium salts on animals, as well as by collecting recorded cases of the therapeutical employment of the drug or its accidental effects as a toxic agent in the human subject. The salt he mainly used was the chloride, a substance with which every one is perfectly familiar in the laboratory, if not in the dispensary. The chief action of Barium appears to be on the heart, showing great similarity to the action of Digitalis, and somewhat less to that of Physostigma. Thus it was found by experiments on frogs that in small doses Barium increased the action of the heart-muscle, and in large doses set up peristaltic movements, arresting the heart finally in systole, this arrest in systole being a tetanic spasm of the heart-muscle, and being capable of being brought to an end by agents which paralyze muscles and by mechanical distension by fluid pressure, but not by the electric current or by Atropin. In very acute poisoning, either by large doses or by the direct application of the Chloride of Barium to the heart, the frog was found, even after the heart was stopped, to be capable of jumping. Again, the isolated apex was caused to beat by Barium, finally being arrested in systole. The arrest caused by Muscarine and Chloral was brought to an end by using this salt. It was found that arrest in diastole could not be produced under its action by stimulation of the vagus or of the sinus venosus. The effects of Barium on the arrest caused by Muscarin, and the want of result from irritating the vagus, were found not to be due to any paralyzing action of the salt on the vagus. The foregoing effects are as nearly as possible identical with those produced by Digitalis, differing also only in a slight degree form those of Physo-stigma. In warm-blooded animals Barium in small doses slows the pulse independently of the inhibitory apparatus. In large doses it first accelerates the pulse, probably by stimulating the accelerating nerve, and finally slows it, in consequence of weakness of the heart. The blood-pressure is greatly increased by Barium. Like Pilocarpin, Barium increases in a marked manner the secretion of saliva, but only when it is injected into the veins, this activity being immediately checked by Atropin, differing in this latter respect from Physostigma. In view of the considerable contraction of the vessels caused by the Chloride of Barium, Professor Kobert has recently made some trials of its use in cases of dilated cutaneous veins, employing it in the form of ointment.
“The cases were one of caput medusae following renal tumor and a case of long-standing dilatation of the veins of the inner aspect of the thigh in a patient with cardiac disease.
“No beneficial effect was obtained. It is, however, probable that by extended observation on physiological principles some valuable therapeutical uses may be found for Barium.”
This cardiac remedy was first used by our school, and for twenty years or more we were the sole prescribers of it.
For the last five years other schools have used it, first the eclectic, and now the regular. The late Austin Flint, in his Clinical Medicine, mentions Cactus as “a valuable cardiac nervine and tonic, in five minim doses.” Dujardin Beaumetz, of France, quotes from Dr. Goss (Mat. Medorrhinum) and Dr. Kunze (New Preparations) several cases of palpitation, hypertrophy, etc., in which Cactus proved of value.
It is singular that F. Lauder Brunton did not appropriate it, together with his wholesale teachings from our Materia Medica. It is now used very extensively by all schools, but I doubt if it has come up to the expectations of some members of our school of practice.
It was heralded by the most fulsome laudations of its great value, not only in diseases of the heart, but in all other acute inflammations. I do not remember, however, to have seen any recent record of diseases other than disorders of the heart cured by the Cactus.
It is my opinion, from careful observation and study of its action, that all the symptoms and conditions caused and cured by Cactus are due to its affinity for the heart and its pathogenetic action thereon.
It appears to me that its action on the heart is that of an intense irritant of the ganglia of that organ. It may thereby cause the several conditions of hyperaesthesia, irritability, neuralgia, spasm, irregular action, and, finally, inflammation. It differs from Digitalis in this, that it seems to have an action on the spiral fibres of the muscular tissue of the heart, while Digitalis acts on all the muscular fibres alike.