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ther； and by nitrous oxid。 In addition our tests have shown that under ether the increase of the H…ion concentrationacidityis more gradual than under nitrous oxid； an observation which accords well with the fact that nitrous oxid more quickly induces anesthesia than does ether。
Further striking testimony in favor of the hypothesis that the production of acidity by inhalation anesthetics is the method by which anesthesia itself is produced is found in the fact that although lethal doses of acid cause muscular paralysis； yet this paralysis may be mitigated by adrenalinwhich is alkaline。 This observation may explain in part the remarkable success of the method of resuscitation devised by me； in which animals 〃killed〃 by anesthetics and asphyxia are revived by the use of adrenalin。
In animals under inhalation anesthesia Williams found that no nerve…current could be detected by the Einthoven string galvanometer； a fact which might be explained by postulating that nerve…currents can flow from the brain to the muscles and glands only when there is a difference of potential。 Any variation from the normal alkalinity of the body must change the difference in potential。 Since the nerve…currents in animals under anesthesia are not demonstrable by any apparatus at our command； and since anesthesia produces acidity； then we may infer that acidity reduces the difference in potential。 As long as there is life； a galvanometer of sufficient delicacy would perforce detect； a nerve…current until the acidity increased to such a point as to reduce the difference in potential to zero the point of death。 If at this point a suitable alkali adrenalin solutioncan be introduced quickly enough； the vital difference in potential may be restored and the life processes will be renewed。 Bearing especially on this point is the fact that if adrenalin in sufficient quantities be administered simultaneously with an acid； it will not only prevent the fall in blood…pressure usually caused by the acid； but will also prevent the histologic changes in the brain； adrenals； and liver which are usually caused by the intravenous injection of acids。
This hypothesis regarding the cause of anesthesia and unconsciousness explains and harmonizes many facts。 It explains how asphyxia； overwhelming emotion； and excessive muscular exertion； by causing acidity； may produce unconsciousness。 It explains the acidosis which results from starvation； from uremia； from diabetes； from Bright's disease； and supplies a reason for the use of intravenous infusions of sodium bicarbonate to overcome the coma of diabetes and uremia （Fig。 76）。 It may explain the quick death from chloroform and nitrous oxid； and may perhaps show why unconsciousness is so commonly the immediate precursor of death。
One of the most noticeable immediate effects of the administration of an inhalation anesthetic is a marked increase in the rapidity and force of the respiration。 The respiratory center has evidently been evolved to act with an increase of vigor which is proportional within certain limitsto the increase in the H…ion concentration； whereas the centers governing the voluntary muscles are inhibited。 In this antithetic reaction of the higher cortical centers and the lower centers in the medulla to acidity we find a remarkable adaptation which prevents the animal from killing itself by the further increase in acidity which would be produced by muscular activity。 That is； as the acidity produced by muscular action increases and threatens life； the respiratory action； by which carbon dioxid is eliminated and oxygen supplied； is increased； while the driving power of the brain； which produces acidity； is diminished or even inhibited entirely； that is； the state of unconsciousness or anesthesia is reached。 We conclude first that； without this life…saving regulation； animals under stress would inevitably commit suicide； and； second； that it is probable that the remarkable phenomenon of anesthesia the coincident existence of unconsciousness and lifeis due to this antithetic action of the cortex and the medulla。
In the human； as in the animal； the degree of acidity parallels the depth of inhalation anesthesia。
Within a few seconds after beginning nitrous oxid anesthesia the acidity of the blood is increased。 This rapid acidulation is synchronous with almost instantaneous unconsciousness and increased respiration。 If the oxygen in the inhaled mixture be increased； a decrease in acidity is again synchronous with lighter anesthesia and a decrease in the respiratory rate。
If these premises be sound； we are justified in asserting that the state of anesthesia is due to an induced acidity of the blood。 If the acidity is slight； then the anesthesia is slight and the force of the nerve impulses is lessened； but the patient is still conscious of them。 As the acidity increases associative memory is lost； and the patient is said to be unconscious： the centers governing the voluntary muscles are not inhibited； however； and cutting the skin causes movements。 If the acidity is further increased； there is loss of muscular tone and even the strong contact ceptor stimuli of a surgical operation do not cause any muscular response； and； finally； the acidity may be increased to the point at which the respiratory and circulatory centers can no longer respond by increased effort； and anesthetic death that is； ACID deathfollows。
Certain clinical phenomena are clarified by this theory and serve to substantiate it。 For example； it is well known that inhalation anesthesia precipitates the impending acidosis which results from starvation； from extreme Graves' disease； from great exhaustion； from surgical shock； and from hemorrhage； and which is present when death from any cause is imminent。
We see； therefore； that anesthesia is made possible； first； by the fact that inhalation anesthetics cause acidity； and； second； by the antithetic adaptation of the higher centers in the brain and of the centers governing respiration and circulation。
In deep contrast to the action of inhalation anesthetics is that of narcotics。 Deep narcotization with morphin and scopolamin is induced slowly； the respiratory and pulse…rate are progressively lessened and there is no acidity。
By our researches we have established in what consists the generic difference between inhalation anesthetics and narcotics。 In our experiments no increase in the H…ion concentration was produced by morphin or by scopolamin； no matter how deep the narcotization。 In animals already narcotized by morphin the production of acid by any of the acid…producing stimuli was delayed or prevented。 On the other hand； in animals in which an acidity had already been produced by ether； by shock； by anger； or by fear； the later administration of morphin delayed or inhibited entirely the neutralization of the acidity。 In other words； morphin interferes with the normal mechanism by which acidity is neutralized possibly because its inhibiting action on the respiratory center is sufficient to overcome the stimulating action of acidity on that center； for； as we have stated； the neutralization of acidity is in large measure accomplished by the increased respiration induced by the acidity itself。
SUMMARY
Acidity inhibits the functions of the cerebral cortex； but stimulates those of the medulla。 This antithetic reaction to the stimulus of increased H…ion concentration is an adaptation to prevent animals from committing suicide by over…activity； for the mechanism for the initiation and control of the transformation of energy is in the higher centers of the brain； while an essential part of the mechanism for the neutralization of aciditythe centers governing circulation and respiration is in the medulla。 This explains many clinical phenomena why excessive acidity causes paralysis； why there is great thirst after inhalation anesthesia； after excessive muscular activity； excessive emotionafter all those activities which we have found to be acid…producing； for water； like air； neutralizes acids。 The excessive use of alcohol； anesthetics； excessive work； intense emotion； all produce lesions of the kidney and of the liver。 The explanation is found in the fact that all these stimuli increase the acidity of the blood。 and that； if long continued； the neutralizing mechanism must be broken down and so the end…products of metabolism are insufficiently prepared for elimination。
In view of these considerations we may well conclude that the maintenance of the normal potential alkalinity of the blood is to be estimated as the keystone of the foundation of life itself。
INDEX
ABDOMEN； diseases of； phylogenetic association and； 44 Acidity； 227 Adaptive energy； 176 variation in rate of energy discharge； 177 Adrenalin； Cannon's test for； 134； 196 injection of； changes in brain…cells from； 186 Adrenals； 196 brain and； relation of； 1。98 diseases of； effect of； on output of energy； 216 functional study of； 196 histologic study of； 198 Alcohol； changes in brain…cells from； 116 Alkalescence； 227 Anemia； pain of； 77 Anesthesia； 2； 227 anoci…association and； differentiation； 34 effect of trauma under； upon brain that remains awake； 3 inhalation； cause of exhaustion of brain…cells as res