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26

Report on Poisons. By G. L. ROUPELL, M.D., F.R.S.

THE complexity of the functions of the animal body, and their liability to disturbance from a number of causes, must be apparent to the most superficial observer. To those who endeavour to explain what takes place during the disturbed performance of the vital actions, many difficulties present themselves; opposite causes occasion one common and similar result, and the same agent will produce very different effects under circumstances apparently analogous. Whilst, however, there may be thus many conflicting processes exhibited to us, we are satisfied that there are leading principles and general laws in operation which it is our great aim to seek for and discover. We cannot avoid allowing the proposition, "That under actually corresponding circumstances similar effects must ensue." the effects of any substance upon the system, as a poison for example, we Should then differences exist in naturally refer them to modifying influences; at the same time that we explain the production of similar effects from opposite causes, by the agency of fundamental principles, proving simplicity in the laws which regulate our frames.

The object of my former communications has been to illustrate the effects of those poisons which induce an alteration in the vascularity of the different tissues with which they may come in contact, and to portray the appearances exhibited by dissection: on the present occasion some views will be stated concerning the operation of an agent which is constantly eliminated from the system, the effects of which, although not indicated by obvious local changes or capable of elucidation by drawings, appear nevertheless to be highly deserving of consideration and study. Carbonic acid is the agent alluded to; one highly interesting, first, from its producing very marked and injurious consequences if applied in any way to the human body, either internally or externally; secondly, from its immediate connection with one highly important function of our system; thirdly, from the analogy of its effects with some most serious maladies; and fourthly, from the causes which influence its secretion.

It cannot here be requisite to insist upon the necessity for the rejection of all effete matter from the body, or to show the importance of the changes perpetually going on in the circulating fluids. These points will readily be conceded to me; nor will the mischief be questioned arising from the presence of certain principles in the blood, such as bile or urea; but, while these substances have deservedly occupied much attention of late, we are neglectful of an agent far more injurious. The ducts of the liver may be partially, if not entirely closed, for months; the kidneys may be removed, or the secretion of urine may be suspended for more than a week, yet life during that time may be preserved; but should the elimination of carbonic acid from the lungs be prevented for a few minutes, nay, only for a few seconds, life will be placed in imminent peril, if not irrevocably destroyed.

We are well aware that carbonic acid is generated by various processes, for example, by decomposition, both of animal and vegetable bodies, by combustion, by fermentation, as well as by the respiratory apparatus. We are also aware that plants yield it by night; that it is exhaled from the earth in certain situations, and that it is disengaged by chemical action, from compounds of which it forms an ingredient. We are certainly ready to admit that air charged with this gas, from whatever source it may be produced, is positively and highly detrimental. Sir Humphry Davy deemed it not beneath his notice to investigate the condition of the atmosphere rendered impure by persons crowding together in large or public assemblies, and showed that carbonic acid was present in excess in the vitiated air of such meetings. The

experiments of MM. Allen and Pepys, Lavoisier and Seguin, Davy and Berzelius, concerning the exact quantity of this gas evolved during respiration, still occupy the attention of the scientific world; but its effects upon the system seem to me to be yet greatly overlooked and disregarded. The injurious consequences which it produces to those who, by accident or design, may be exposed to its effects, have led to less useful results, practically, than might have been anticipated from the nature of the symptoms, and the interesting phenomena which result from its action. Year after year numbers flock to witness the experiment of submitting a wretched animal to the deadly atmosphere of the "Grotto del Cane," without drawing those deductions, or deriving that advantage from its sufferings, which alone can palliate or justify their infliction.

Carbonic acid has many sources out of the body, and it is abundantly furnished by respiration. The lungs, however, are by no means its only outlet from the animal body. It is given off by the skin, it is secreted as well by the serous as mucous membranes*, points of much interest, not only as affording an example of vicarious action, but as explanatory of various bodily disorders. It cannot here be necessary to controvert old errors respecting the source of the carbonic acid yielded by respiration, nor to dwell upon the more probable views of modern times. The opinions and experiments of Mr. Edwards, which prove that this acid is extricated from the lungs, although no oxygen is respired†, the observations of Professor Magnus, and his conclusions that all blood contains carbonic acid, the belief of Müller that the quantity held in solution in itt is sufficiently large to account for the whole exhaled by the lungs, are facts well known to all whom it is my pleasure to address. Thus we find that a most important series of changes takes place during the circulation of the blood leading to the formation of carbonic acid, which is set free from various surfaces, chiefly, however, from the parietes of the air-cells, which allow it to pass through them in order to be exhaled§. Next we find that many circumstances greatly influence the amount of this gas yielded by respiration; these may be ranked in two classes, one of which may be considered as natural or regular, the other as accidental or abnormal. With regard to the first of these, to the regular performance of the functions of the system, we find that more carbonic acid is eliminated during the day than by night; that it increases at day-break, and diminishes at sunset; that it is produced in larger quantity by exercise and during digestion ; and, what is extremely interesting, we see a tendency to equilibrium in the whole amount; for if given off in excess at one time, at another it will, as a consequence, be lessened. With regard to the second class of circumstances which influence the secretion, we find that it is diminished by depressing passions, debilitating causes, low diet, and injuries to the par vagum¶.

If we now look to the actual effects of carbonic acid, when placed in contact with the living body, many interesting consequences result which serve to indicate its use in the human economy, and its agency in disease.

It imparts an acid taste, produces a sense of burning in the uvula**, and acts instantaneously as a powerful irritant to the muscles of the larynx, occasioning by their spasmodic action the complete and firm closure of the glottis tt. Applied externally to the skin, or taken into the stomach, it occasions giddiness, pain and weight in the head, obscurity of sight, and ringing in the ears‡‡. * Mayo, Phys., pp. 120, 131. Mayo, Path., 336. Müller, Phys., 556. Robert Lee, Cyclopæd. Pract. Med. vol. iv. p. 383.

Mayo, Phys., p. 63.
Müller, ibid.

Müller, p. 328.

§ Müller, p. 330.
¶ Brodie, Phil. Trans., c. ii. p. 390.
Christison on Poisons, 3rd ed., 745.

** Davy on Nit. Ox., p. 472.
Collard de Martigni, Archives, 211. Christison, 2nd ed., pp. 703-706.

tt Ibid.

Inhaled by the breath, it is well known to produce serious and alarming symptoms, varying as the gas may be more or less diluted. The following experiments show its effects when injected into the vessels.

EXPERIMENT I. To show the Effect of Carbonic Acid injected into the Veins.

Two fluid ounces (by measure) of this gas, prepared by the action of diluted hydrochloric acid upon chalk, were collected over water, and thrown slowly, by a syringe, into the external saphæna vein of a strong dog. Almost immediately afterwards the animal exhibited signs of uneasiness, uttered cries of distress, became convulsed, lost its consciousness, and appeared to be dying; it felt, however, the stimulus of cold water when thrown upon it, and quickly recovered upon being removed into the fresh air.

It thus is capable of producing a powerful impression on the system, when thrown into the veins even in a small quantity. Still more marked results ensued when it was introduced into an artery, as was shown in the next experiment.

EXPERIMENT II.-To show the Effects of Carbonic Acid when thrown into the Carotid Artery.

The left external carotid artery was exposed in the same dog, and a small tube was introduced into it, a ligature having previously been applied to prevent hemorrhage: a fluid ounce and a half (by measure) of carbonic acid was then thrown in. This was done gently, but it was necessary to discontinue the experiment, in consequence of the animal becoming convulsed and foaming at the mouth. After forty seconds it seemed to recover; but again relapsed, lost all consciousness and power of movement, was quite insensible, and lay as if dead upon the floor. At intervals of a few minutes it was seized with attacks of violent spasms. This alternation of stupor and convulsions continued for four hours, when the animal regained its senses, the power of its limbs, and appeared afterwards to suffer no inconvenience.

M. Nysten considers that the effects witnessed on throwing carbonic acid into the vessels arise from the distension of the right side of the heart; this seems, however, questionable in the experiment just detailed, as the gas was injected slowly in a direction from the heart, and produced other symptoms than those described as arising from the simple admixture of air with venous blood*. This eminent experimentalist certainly errs in considering that carbonic acid is not itself intrinsically poisonous. It cannot be necessary to pause in order to refute this idea, but it is worth while to mention the diversity in its effects: some speak of experiencing a lively sensation of pleasure on respiring it; others, of the sensation of a gentle heat and perspiration ; and Sir Humphry Davy said he could answer, from his own experience, that no pain precedes the insensibility occasioned by breathing gases unfitted for supporting life. In general, however, vertigo, head-ache, accelerated pulse, hurried breathing, palpitation of the heart, tendency to sleep, ending in complete loss of consciousness, with convulsions, mark its effects during life; whilst retention of the warmth of the body, flexibility of the limbs, fluidity and blackness of the blood, characterise after death the bodies of those poisoned by this gas.

If we now turn to those diseases, the leading symptoms of which bear resemblance to the effects of carbonic acid, we find them to be such as prevent the proper arterialization of the blood, emphysema of the lungs, diseases of the heart; or, to be brief, all such as impede respiration, in which cases we find betude of mind, torpor of body, inclination to doze, spasmodic respiratory + Salmonia, p. 112.

* Mayo, Phys., p. 72.

movements, and the tendency to convulsive muscular action. It is not, in truth, novel to refer these symptoms to the accumulation of carbon in the system; but, close as the similarity in many respects undoubtedly is in these instances, the disorder in which we have the nearest resemblance, and which seems as if it were its true prototype, is still the Opprobrium Medicorum. We have in the symptoms produced by carbonic acid, the counterpart of those exhibited in epilepsy; no less instantaneous is the attack of this appalling malady, than are the effects of the sudden closure of the glottis by the irritation of the choke damp, or other exposure to fixed air, by persons descending into vats, or breathing the gas given off by fermentation. Plunge an animal into it, or inject it into the veins, and we can at will produce epilepsy with all its terrific features and depressing consequences.

The curious coincidence of the diminished secretion of this acid from the lungs, towards evening, when the natural tendency to sleep comes on; the increase in its quantity at day-break, when epileptic seizures are most likely to occur; the hurried and spasmodic respiration, when it is present in excess, are valid arguments for the belief that it may be an active agent in exciting both healthy and disordered functions.

Carbonic acid acts upon the medulla oblongata, for it annihilates volition and consciousness, which have their seat in this portion of the nervous centres. The medulla oblongata also, be it observed, is the source of the respiratory movements*. How these are called into action we are yet in doubt; that they may be excited primarily and throughout life by the stimulus of carbonic acid, is advanced as a conjecture, which derives abundant support from the analogy of other excretions.

gas,

Minute details would here be out of place, or the quantity of this capable of producing injurious consequences, and the peculiarities of individuals rendering them especially liable to its influence, might be entered into. Suffice it, that extremely minute portions of gaseous bodies, as shown in the instance of the odour of musk, or the fragrance of flowers, is enough to produce the most decided effects.

It were tedious to enter into collateral inquiry, or to combat objections which may be advanced against the ideas thus submitted to the Association. It is doubtless extraordinary that an acid should be formed in the blood, and given off, instead of combining with the alkali of the serum. The insensibility of animals confined in nitrogen or hydrogen gases, in which the quantity of carbonic acid nearly equals that by natural respiration, may be otherwise explained; new combinations may form; carburetted hydrogen, for instance, may be generated, which would itself poison the animal; and we should not forget the fact, that the insensibility, occasioned under the circumstances. alluded to, is found to be much more easily dissipated than that which arises from the prevention of the escape of carbonic acid from the body.

From this we might pass on to various spasmodic disorders, but it were perhaps premature to say anything further on this head; only one more point shall be noticed in connection with this subject, and that is the resemblance in the effects of narcotic poisons to those arising from carbonic acid. Reflections upon these facts have led me to think that this gas may play an essential part in the phenomena exhibited by narcotics, a class of substances, the operation of which is so little understood, but the action of which is obviously upon the functions of the system, rather than upon the vascularity of its organs. It has long been laid down as a rule, that opium is not to be exhibited when the blood is not properly aërated or decarbonised.

Many experiments have been made by me to ascertain whether any difference * Müller, pp. 348, 351, 827, 918.

existed in the quantity of carbonic acid given off from the system, when under the influence of opium. With this view the quantity eliminated before and after a dose of this drug had been taken, has been repeatedly measured. The experiments were performed by breathing through a solution of pure potassa, and by weighing the result, as well as extricating the carbonic acid acquired. It is unnecessary to enumerate the modifications in the apparatus used, in order completely to separate the watery vapour, to prevent the chloride of calcium employed for this purpose from descending into the potassa and negativing the result, to obviate the escape of minute portions of the solution of potassa on passing the expired air through it; the conclusion arrived at is, that much more carbonic acid is given off simultaneously with the production of the effects of opium. Not only is the number of respirations increased, and thus more is eliminated, but in an equal number of respirations there was found to be an increase of at least one-tenth. The quantity of opium taken was equivalent to a grain and a half of the extract, and the observation was made as soon as the effects (tightness of the forehead, slight sensation of nausea, accelerated pulse, quickened breathing, and general feeling of tranquillity) were perceived. It were easy to show the general likeness of the action of narcotics to those produced by carbonic acid gas; but to connect them with this last-named agent will require further inquiry.

Allow me now, in conclusion, to state that the ideas expressed in this paper, are submitted with great deference to the Meeting; that they are advanced with the view of calling attention to certain interesting but obscure phenomena, and are forwarded in compliance with the desire of the Association. 15 Welbeck Street, July 1841.

Report on Discussions of Bristol Tides, performed by Mr. BUNT under the direction of the Rev. W. WHEWELL, F.R.S. [With Plates 2, 3, 4, 5.]

THE careful and intelligent manner in which Mr. Bunt had conducted those Discussions of the Tides, on which the grants of the British Association in former years had enabled me to employ him, made me very desirous of continuing to profit by his labours, in order to bring, if possible, the ascertained laws of the tides nearer to the observations. With this view I applied at the last meeting for an additional grant of 50%.; and have now to report the progress which has been consequently made in our tide discussions. We began by considering the possibility of improving the correction for lunar declination, and the determination of the anterior epoch of the semimenstrual inequality. But it did not appear very probable that any additional discussion of the observations which we had before us would give us any additional accuracy, commensurate with the great labour which must be undergone in making the trial. I was therefore the more ready to follow out a suggestion of Mr. Bunt's, who wrote to me in January last that he had recently determined to try whether he could perceive any effect on the heights of high water at Bristol produced by atmospheric pressure. He adds, "I accordingly arranged the errors of the calculated heights for 1840 in columns for every two-tenths of an inch of the barometer, observed contemporaneously with the tide."

From a diagram given in his letter, the average effect appeared to be about 15 inches depression of high water to 1 inch rise of mercury in barometer. The consistency of these results leaves no doubt as to the fact of a sensible effect on the heights from this cause. In his letter, he adds, In his letter, he adds, "Some subsequent trials

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