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r； the cardiac； and the respiratory centers discharge energy in response to traumatic stimuli applied to various sensitive regions of the body during surgical anesthesia。 If the trauma be sufficient； exhaustion of the entire brain will be observed after the effect of the anesthesia has worn off； that is to say； despite the complete paralysis of voluntary motion and the loss of consciousness due to ether； the traumatic impulses that are known to reach the AWAKE centers in the medulla also reach and influence every other part of the brain。 Whether or not the consequent functional depression and the morphologic alterations seen in the brain…cells may be due to the low blood…pressure which follows excessive trauma is shown by the following experiments： The circulation of animals was first rendered STATIC by over…transfusion； and was controlled by a continuous blood…pressure record on a drum； the factor of anemia being thereby wholly excluded during the application of the trauma and during the removal of a specimen of brain tissue for histologic study。 In each instance； morphologic changes in the cells of all parts of the brain were found； but it required much more trauma to produce brain…cell changes in animals whose blood…pressure was kept at the normal level than in the animals whose blood…pressure was allowed to take a downward course。 In the cortex and in the cerebellum； the changes in the brain…cells were in every instance more marked than in the medulla。
There is also strong NEGATIVE evidence that traumatic impulses are not excluded by ether anesthesia from the part of the brain that is apparently asleep。 This evidence is as follows： If the factor of fear be excluded； and if in addition the traumatic impulses be prevented from reaching the brain by cocain＇*＇ blocking； then； despite the intensity or the duration of the trauma within the zone so blocked； there follows no exhaustion after the effect of the anesthetic disappears； and no morphologic changes are noted in the brain…cells。
＇*＇ Since the presentation of this paper； novocain has been substituted for cocain in operations under anoci…association。
Still further negative evidence that inhalation anesthesia offers little or no protection to the brain…cells against trauma is derived from the following experiment： A dog whose spinal cord had been divided at the level of the first dorsal segment； and which had then been kept in good condition for two months； showed a recovery of the spinal reflexes； such as the scratch reflex； etc。 Such an animal is known as a 〃spinal dog。〃 Now； in this animal； the abdomen and hind extremities had no direct nerve connection with the brain。 In this dog； continuous severe trauma of the abdominal viscera and of the hind extremities lasting for four hours was accompanied by but slight change in either the circulation or in the respiration； and by no microscopic alteration of the brain…cells （Fig。 1）。 Judging from a large number of experiments on NORMAL dogs under ether； such an amount of trauma would have caused not only complete physiologic exhaustion of the brain； but also morphologic alterations of all of the brain…cells and the physical destruction of many （Fig。 2）。 We must； therefore； conclude that； although ether anesthesia produces unconsciousness； it APPARENTLY PROTECTS NONE OF THE BRAIN…CELLS against exhaustion from the trauma of surgical operations； ether is； so to speak； but a veneer。 Under nitrous oxid anesthesia there is approximately only one…fourth as much exhaustion as is produced by equal trauma under ether （Fig。 3）。 We must conclude； therefore； either that nitrous oxid protects the brain…cells against trauma or that ether predisposes the brain…cells to exhaustion as a result of trauma。 With these premises let us now inquire into the cause of this exhaustion of the brain…cells。
The Cause of the Exhaustion of the Brain…cells as a Result of Trauma of Various Parts of the Body under Inhalation Anesthesia
Numerous experiments on animals to determine the effect of ether anesthesia _per se_； _i。 e_。； ether anesthesia without trauma； showed that； although certain changes were produced； these included neither the physiologic exhaustion nor the alterations in the brain…cells which are characteristic of the effects of trauma。 On turning to the study of trauma； we at once found in the behavior of individuals as a whole under deep and under light anesthesia the clue to the cause of the discharge of energy； of the consequent physiologic exhaustion； and of the morphologic changes in the brain…cells。
If； in the course of abdominal operations； rough manipulations of the parietal peritoneum be made； there will be frequently observed a marked increase in the respiratory rate and an increase in the expiratory force which may be marked by the production of an audible expiratory groan。 Under light ether anesthesia； severe manipulations of the peritoneum often cause such vigorous contractions of the abdominal muscles that the operator is greatly hindered in his work。
Among the unconscious responses to trauma under ether anesthesia are purposeless moving； the withdrawal of the injured part； and； if the anesthesia be sufficiently light and the trauma sufficiently strong； there may be an effort toward escape from the injury。 In injury under ether anesthesia every grade of response may be seen； from the slightest change in the respiration or in the blood…pressure to a vigorous defensive struggle。 As to the purpose of these subconscious movements in response to injury； there can be no doubt THEY ARE EFFORTS TO ESCAPE FROM THE INJURY。
Picture what would be the result of a formidable abdominal operation extending over a period of half an hour or more on an unanesthetized human patient； during which extensive adhesions had been broken up； or a large tumor dislodged from its bed！ In such a case； would not the nervous system discharge its energy to the utmost in efforts to escape from the injury； and would not the patient suffer complete exhaustion？ If the traumata under inhalation anesthesia are sufficiently strong and are repeated in sufficient numbers； the brain…cells are finally deprived of their dischargeable nervous energy and become exhausted just as exhaustion follows such strenuous and prolonged muscular exertion as is seen in endurance tests。 Whether the energy of the brain be discharged by injury under anesthesia or by ordinary muscular exertion； identical morphologic changes are seen in the nerve…cells。 In shock from injury （Fig。 2）； in exhaustion from overwork （Hodge and Dolley） （Fig。 4）； and in exhaustion from pure fear （Fig。 5）； the resultant general functional weakness is similar in each case a certain length of time is required to effect recovery； and in each there are morphologic changes in the brain…cells。 It is quite clear that in each of these cases the altered function and form of the brain…cells are due to an _*excessive discharge of nervous energy_。 This brings us to the next question： What determines the discharge of energy as a result of trauma with or without inhalation anesthesia？
The Cause of the Discharge of Nervous Energy as a Result of Trauma under Inhalation Anesthesia and under Normal Conditions
I looked into this problem from many viewpoints and there seemed to be no solution until it occurred to me to seek the explanation in certain of the postulates which make up the doctrine of evolution。 I realize fully the difficulty and the danger in attempting to reach the generalization which I shall make later and in the hypothesis I shall propose； for there is； of course； no direct final proof of the truth of even the doctrine of evolution。 It is idle to consider any experimental research into the cause of phenomena that have developed by natural selection during millions of years。 Nature herself has made the experiments on a world…wide scale and the data are before us for interpretation。 Darwin could do no more than to collect all available facts and then to frame the hypothesis by which the facts were best harmonized。 Sherrington； that masterly physiologist； in his volume entitled 〃The Integrative Action of the Nervous System；〃 shows clearly how the central nervous system was built up in the process of evolution。 Sherrington has made free use of Darwin's doctrine in explaining physiologic functions； just as anatomists have extensively utilized it in the explanation of the genesis of anatomic forms。 I shall assume； therefore； that the discharge of nervous energy is accomplished by the application of the laws of inheritance and association； and I conclude that this hypothesis will explain many clinical phenomena。 I shall now present such evidence in favor of this hypothesis as time and my limitations will admit； after which I shall point out certain clinical facts that may be explained by this hypothesis。
According to the doctrine of evolution； every function owes its origin to natural selection in the struggle for existence。 In the lower and simpler forms of animal life； indeed； in our human progenitors as well； existence depended principally upon the success with which three great purposes were achieved： （1） Self…defense against or escape from enemies； （2） the acquisition of foo