340 



NATURE 



{Aug. 17, 1876 



life had ceased. Thus it was shown that nitrite of amyl 

 was not an anaesthetic. It did not produce sleep. 



After the life of the animals of warm blood was sud- 

 denly extinguished by the vapour, — and apparently the 

 extinction was without pain, — I remarked that the in- 

 ternal organs of the body after the death were in some 

 instances exceedingly congested with blood. The lungs 

 and the brain were commonly in this state ; but it struck 

 ine, though I could not explain the fact at the moment, 

 that exceptionally these organs, when the death of the 

 animal was instantaneous, were left quite bloodless, and 

 actually white in their texture. Further, I observed that 

 in the warm bloods the muscular irritability remained for 

 a very long time after death, often for many hours. These 

 phenomena were strange on the warm-blooded animals, 

 but they were trifling in comparison with what was ob- 

 served on cold-blooded animals. I discovered that in the 

 frog the complete insensibility, and, as it seemed, absolute 

 death, produced by the nitrite was not death really, but a 

 suspended animation, a condition like that which has 

 been called trance in the human subject. A condition of 

 simulated death so perfect that no sign of life could be 

 obtained, and yet from which, after so long an interval of 

 time as nine days, the animal would wake up and enter 

 again into life as if nothing had been done to derange its 

 life. During all this time the limbs of the animal re- 

 mained mobile ; not a muscle was stiffened into the 

 rigidity of death. There was induced, in fact, not only 

 the trance of the human subject, but the corresponding 

 cataleptic state of the muscular fibre. In addition I 

 learned that during this state of suspense of life, the blood, 

 though it was darkened and deprived of its capacity of 

 becoming oxidised, and otherwise changed, was held in the 

 fluid state. Like the muscles, it remained free of the 

 change called pectous ; it did not coagulate. 



The next step in the investigation had relation to the 

 action of the nitrite on the vessels which constitute the 

 minute circulation. The change in the circulation in 

 the web of the frog under its influence was carefully in- 

 vestigated ; the condition of the circulation through the 

 semi-transparent ear of the rabbit while the animal was 

 breathing the vapour was also carefully investigated. 

 The result of these inquiries was to discover that nitrite 

 of amyl exerts a direct action on the nervous function, 

 and that the action consists of a paralysing influence on 

 the nervous mechanism by which the minute arterial 

 system is controlled and governed. To repeat the words 

 of the report I made to the meeting at Newcastle, 

 " the action of the nitrite was directly on the nervous 

 system, and that such action, transferred to the filaments 

 of nerves surrounding the arteries, paralysed the vaso 

 nerves, on which the heart immediately injected the 

 vessels, causing the peculiar redness of the skin and the 

 other phenomena that have been narrated." 



In this preliminary inquiry I advanced the new propo- 

 sitions that we had in our possession a chemical sub- 

 stance which, being introduced into the body, overcomes 

 the arterial tonicity, and causes phenomena analogous to 

 those changes in the vascular current which follow upon 

 division of the sympathetic nerve. 



I further suggested that in cases of trance and cata- 

 lepsy in the human sutyect, some substance analogous in 

 its action to the nitrite is produced in the body by some 

 error of secretion, some modification of the animal che- 

 mistry, and that the foreign substance so engendered is 

 the cause of the disease. The first of these propositions 

 is, I consider, proven ; the second is not proven by any 

 new research, but is still the most reasonable exposition 

 of the phenomena to which it refers. 



In continuation of experiment on the action of the 

 nitrite of amyl on the nervous system, I studied next its 

 local action, and came to the conclusion that its action 

 on the nervous matter is not through the blood, but by 

 direct impression through the nervous cords to the vas- 



cular motor nervous supply. I compared other bodies 

 of the nitrite order — such as nitrite of methyl, ethyl, and 

 butyl — with it in their operation. I compared it in its action 

 with emotional shocks, and correlated the blush on the 

 cheek or the pallor of the cheek which it produces with 

 the blush or pallor induced by the impressions creating 

 shame, fear, or other similar passions. I traced, through 

 the whole of the phenomena induced by the agent, the 

 action of the base amyl, and the effect of the addition of the 

 elements, nitrogen and oxygen ; and I showed that when 

 oxygen and nitrogen are brought into combination with 

 the base, the physiological effect is modified and the 

 specific influence of the substance on the vascular sys- 

 tem is declared. I was led to compare the action of 

 nitrite of amyl with other chemical bodies, and, using it 

 as a key, was enabled to show the analogical action of 

 many other compounds. Notably, I pointed out from 

 the observations collected during this inquiry, that alco- 

 hol produces its influence on the extreme vascular system 

 by the same paralysing process. By investigating the 

 effect of the agent after its long- continued inhalation, I 

 was able to show that it induces changes in the circu- 

 lation of the lung which lead to congestions and even to 

 haemorrhages like those which occur in some forms of 

 pulmonary consumption, and thus the nervous origin of 

 consumption of the lungs was brought fairly under notice 

 as a new element of study in the clinical history of that 

 fatal disease. In yet another series of observations I 

 learned that rabbits afflicted with a singularly loath- 

 some skin disease — resembling lepra in man — re- 

 cover rapidly in an atmosphere containing the nitrite 

 vapour ; that the dry and colourless and scaly skin of the 

 animals become suffused with blood ; that with this 

 increased capillary circulation the scales fall off and 

 healthy skin begins to appear ; that the fur of the animals 

 begins to grow ; that the general nutrition of the animals 

 is soon improved, and that within a month their cure is 

 completed. 



From my point of view the disclosure of these facts 

 alone were a sufficient vindication of the line of research 

 by experiment on living animals pursued with the nitrite 

 of amyl. They were, however, very poor indeed, when 

 they are compared with another disclosure of fact which 

 came out of the same experimental research. 



In 1863 I had learned that the influence of the nitrite 

 of amyl was on the nervous vascular supply, that it para- 

 lysed temporarily the nervous action, and that the vascu- 

 lar redness it induces is due to this paralysis. In the 

 succeeding year I followed up this subject more closely, 

 and by an extension of observation I was led to the con- 

 clusion that in the nitrite of amyl we had found the most 

 potent chemical agent that had ever been discovered for 

 overcoming muscular spasm generally. The singular 

 cataleptic and passive state of the voluntary muscles was 

 an evidence of this fact, and it tallied with the earlier 

 observation of the effect on the vascular tension. In 

 addition, I saw that in this nitrite I held a sub- 

 stance which would not fix itself with the tissues of the 

 animal and require to be eliminated by the slow process 

 of fluid excretion through the kidney ,or skin, but that, 

 owing to its insolubility and volatility, it would escape by 

 the organs of respiration as well as by the other channels 

 of elimination. I had learned, indeed, that in animals 

 like frogs, from the bodies of which, owing to the thick- 

 ness of the cutaneous tissue, the transpiration is easy, the 

 spontaneous evaporation of the nitrite, extending over the 

 long period of nine days, was sufficient of itself to lead to 

 restoration of vital function. The study of the whole 

 series of facts, when the facts were carefully collected and 

 weighed, led to the demonstration that the original view 

 as to the nitrite of amyl being a stimulant and an extreme 

 excitant was wrong ; it disclosed that the phenomena of 

 excitation, as they at first seemed, were phenomena really 

 of suppressed nervous function, that the vascular injeCT 



