The fact here established explains in the simplest manner the often described observation that in the human being and in mammals during prolonged anæsthesia typical products of insufficient combustion, such as fatty acids, lactic acid and above all aceton, in not inconsiderable quantities are eliminated, as the case may be, by the urine or the respiratory air.[216] If, as has been shown by the foregoing experiments, the processes of disintegration can continue to anoxydatively take place during narcosis, the problem arises, if this anoxydative breaking down can be further increased by excitating stimuli. This question has been answered likewise by means of experiments on the nerve made by Heaton.[217] The two sciatic nerves of the same frog were drawn through a double glass chamber of the form previously described so that each nerve lay on an electrode and with the central stump protruding out of the chamber hanging likewise over an electrode. As in the former instances the muscle contraction of the shank again served as indicator. Both nerves were then subjected to the same current of nitrogen-ether. When, as a result of the narcosis, their irritability has sunk to the level of “stromschleifen” the central stump of the one nerve was continuously stimulated with faradic shocks during a prolonged period, while the other nerve remained at rest. Finally, by displacement of the current of nitrogen-ether with one of pure nitrogen, cessation of narcosis was brought about. It was then seen that the irritability of the continuously stimulated nerve showed a much greater decrease than that of the nonstimulated. The control made by introduction of air demonstrated that both nerves recovered in an oxygen supply. There can, therefore, be no doubt, by comparative experiments we find, that during narcosis anoxydative disintegration can be still further increased by the action of stimuli.
In view of this knowledge of the influence of narcotics on oxygen exchange it may be considered as a firmly established fact, that a process of depression is developed during narcosis, which can be classified with the large group of depressions, resulting from deficiency of oxygen. This is followed by the important problem, is it possible to attribute the whole series of alterations, produced by the narcotic, solely to this one factor? In other words, is narcosis the result of acute suppression of the oxydative processes?
If the individual symptoms which characterize narcosis are investigated from this point of view, one must indeed confess that they are all readily understood when regarded as the results of suppression of the oxydative processes. Indeed, the disappearance of the perceptible vital activities, the decrease of irritability, the restriction of the conduction of excitation, the continuance of an anoxydative breaking down, the recovery on cessation of narcosis, provided oxygen is present, etc., in short, all the characteristics of narcosis so far known must be expected and demanded if a suppression of the oxydative processes exists during narcosis.
There is only one point which at the first glance would not seem to agree entirely with the assumption. This is the fact that depression sets in with a relatively greater rapidity in narcosis than when the supply of oxygen is completely withdrawn. Depression of the centers in the spinal cord, which begins in about five to ten minutes after artificial circulation of an oxygen-free, alcohol-containing, saline solution, is not brought about for more than an hour when the same saline solution but without alcohol is introduced. This difference is still more strikingly apparent in the nerve. The same degree of depression, which is produced in the nerve in a nitrogen-ether mixture within about five minutes, is not reached in pure nitrogen without ether until after the lapse of from two to four hours. In order to investigate this relation somewhat more closely I have questioned if it is possible for a living system, which has been narcotized to a certain extent, to regain its irritability in a completely oxygen-free medium, if cessation of the narcosis takes place after a period essentially shorter than the time of asphyxiation of the system under equal conditions. If the depression of narcosis is founded exclusively on asphyxiation, it would be expected that no recovery could occur. Experiments which I have made on the spinal cord centers as well as on the peripheral nerves have, however, demonstrated exactly the contrary. If a frog is subjected to an artificial circulation of an oxygen-free saline solution containing 5 per cent. of alcohol until reaction is lost, being certain of this by the injection of a weak dose of strychnine, and if now a cessation of the narcosis is brought about by the transfusion of oxygen-free saline solution, the centers of the animal recover completely within ten to fifteen minutes, as shown by typical strychnine tetanus. If a nerve is placed in a gas chamber through which a mixture of nitrogen and ether is allowed to flow until irritability is greatly decreased, and is then displaced by pure nitrogen, irritability increases more or less completely according to the time which has passed from the beginning of asphyxiation. This investigation proves that living substance, even after the deepest narcotic depression, may recover on cessation of the narcosis, although in an entirely oxygen-free medium. Fröhlich, Bondy and Heaton, by the methods of their experiments above described, have proved this fact in a great number of instances. On the other hand, Ishikawa could not observe a pronounced recovery in amœbæ from narcosis in pure nitrogen. But it is possible that here the difference is perhaps merely quantitative.
What position should be taken in the face of these facts? Does recovery of a deeply narcotized tissue in an oxygen-free medium really make it difficult to suppose that narcosis is the result of an acute suppression of the processes of oxydation? On closer view, it will be found that this difficulty is merely apparent. In reality it is quite possible to bring these facts into harmony with the assumption that narcosis consists in a suppression of these processes. If one proceeds from the supposition that living substance possesses a certain, even though merely a small supply of oxygen in its interior, then it is at once evident that a more or less complete recovery of irritability from narcosis depression is possible, even in an oxygen-free medium. It can take place at the cost of the oxygen still present in the living substance and which during the narcosis, on account of the suppression of the oxydation processes, could not be consumed. If the presence of a certain oxygen reserve in living substance is entirely set aside and a different explanation sought for the primary continuance of irritability after a complete withdrawal of the oxygen supply from without, the great difference of time in the setting in of the depression in narcosis and that of the complete elimination of the oxygen supply from without would make it necessary to assume the processes occurring in narcosis are entirely different in nature. The explanation that narcosis is the result of suppression of the oxydative processes would indeed be out of the question in such a view.
The assumption, however, that in a living system at the same moment when oxygen is removed from the neighborhood, let us say by a stream of nitrogen, no oxygen would be present and that in consequence every oxydative process must cease, contains so little probability that I have rejected it on various occasions.[218] The way in which irritability is lost in asphyxiation of the nerve likewise very clearly demonstrates the untenability of this view. The recent investigations of Lodholz[219] have shown that decrease of irritability takes place after a sudden displacement of all oxygen from the surrounding medium uniformly and gradually in the form of a logarithmic curve. If at the moment of oxygen withdrawal from the outer medium, metabolism became entirely anoxydative, the curve of irritability must under all circumstances show a sudden steep decline at this point, and subsequent to this a further slower decrease. For, as the oxydative processes constitute by far the chief part in the energy production of living substance, the production of energy, and with this irritability, would undergo considerable loss at the same moment in which oxydative was replaced by anoxydative disintegration. The curve of decrease of irritability during the transition period from oxygen supply to oxygen withdrawal shows, on the contrary, a completely uniform course and it is not until later that a very slow decline takes place, which only after a prolonged time assumes increasing rapidity. But the assumption that at the moment when the supply of oxygen ceases, anoxydative breaking down could acquire such enormous dimensions that it furnishes just exactly the same amount of energy as was before supplied oxydatively, is a view which no one will seriously entertain. In connection with this I wish to call attention to the experiments of Fröhlich[220] in which he compared the time required for asphyxiation to take place in the nerves, when, on the one hand, the frogs had been kept several days previous to the experiment in temperature of 14–40° C., and on the other, in one merely a few degrees above zero. He found that the nerves of the cooled frogs required on an average twice or three times as long for their irritability to sink to the same degree as those of the heated frog, although during the experiment the same temperature was present in both. It was also shown that the asphyxiation period was prolonged up to a certain limit, depending upon the length of time the animals were kept at a low temperature. It would seem to me that these facts admit of no other explanation than that in a low temperature a greater amount of oxygen is stored in the nerve than in high temperatures. From the standpoint that from the moment of withdrawal of oxygen from without, disintegration likewise takes place exclusively anoxydatively, these facts would be completely incomprehensible. When, however, the assumption is made, and this would appear to me as inevitable, that living substance contains in itself a certain even though a very slight quantity of oxygen, which in low temperature is greater, in a high temperature less, the recovery from narcosis, when oxygen is withheld, is not at all surprising. The comparatively rapid setting in of depression in narcosis finds a simple explanation in the violent manner in which the oxydative breaking down, notwithstanding the presence of oxygen, is suddenly suppressed by the flooding by the narcotic. Finally, this view receives unlooked-for support by a group of facts which at the first glance would appear to bear no relation whatever to the process of narcosis.
In a series of investigations on the mechanism of movement in naked protoplasm,[221] I have pointed out the rôle played by oxygen in the genesis of the amœboid protoplasm movement. We can distinguish two antagonistic phases in the movement of amœboid cells, the expansion phase and the contraction phase. The first consists in an increase, the latter in a diminution of the surface, the mass remaining the same. The expansion phase is manifested in the stretching out of the pseudopods by a centrifugal outflowing of the protoplasm into the surrounding medium, the contraction phase by the indrawing of the pseudopods by the centripetal inflowing of the protoplasm to the cell body. In total contraction, such as occurs, for instance, in strong excitation following stimuli, the cell body becomes ball shaped. In local contraction of the long thread or net-shaped outstretched pseudopods of the sea rhizopoda, the protoplasm of the retracting pseudopod forms balls and spindles. Considered from a physical point of view the expansion phase of amœboid movement is an expression of decrease, the contraction phase an increase of the surface tension. I have shown that the factor which under physiological conditions decreases the surface pressure and thereby brings about the expansion phase is the introduction of oxygen into the living substance. With removal of oxygen the stretching out of the pseudopods ceases. The cell gradually draws in all pseudopods and assumes the shape of a ball. On the reintroduction of oxygen the outflow of the pseudopods begins anew. This fact can be observed in all amœboid cells. When, therefore, consumption of oxygen and oxydative changes is suppressed during narcosis it is to be expected that all naked protoplasm masses by being narcotized lose their capability of assuming the expansion phase of movement and contract into the shape of balls. Experimentation confirms this deduction in the most striking manner. When amœbæ are placed in a drop of water under the microscope in a gas cell through which air and a little ether are allowed to flow, the pseudopod formation of the amœbæ ceases within a few minutes and they all assume the shape of a ball. (Figure [62].) In asphyxiation in pure nitrogen, the changes in the amœbæ take place in exactly the same manner with the exception that in this case a longer period ensues according to the size and activity of the animals. About 20 to 60 minutes elapse before depression becomes complete. If larger sea rhizopoda are narcotized in the same manner all pseudopods are more or less retracted and the contained protoplasm flows centripetally and contracts in the characteristic manner into balls and spindles. (Figure [63].) If the narcosis is removed by displacing the ether by pure air, the stretching out of the pseudopods then begins anew, provided the narcosis has not been too deep or too prolonged.
Fig. 62.
Amoeba limax. A—In normal state. B—Narcotized by ether.