322 Transactions, 



excitability of the medullary centres, and the stronger reflex effects from 

 these usually lead to a rise of blood-pressure ; but in cases where some 

 reflex cardiac inhibition already obtains, this is increased by tutin, and a 

 fall in pressure results. That tutin acts specially on the centres in the 

 medulla was also shown in several experiments where Traube-Hering curves 

 and Cheyne-Stokes type of respiration occurred simultaneously. When 

 twitching and general convulsions set in, the blood-pressure curve became 

 markedly irregular, due probably to mechanical obstruction to the flow 

 through the vessels. 



The action of tutin on the vagus-endings in the heart was investigated. 

 The strength of stimulus just necessary to inhibit the heart slightly and 

 cause a fall of blood-pressure was determined both before and after the 

 injection of tutin. No marked difference was obtained, so it was con- 

 cluded that tutin has no influence on the excitability of the nerve-ending 

 in the heart. 



In some of the later experiments a spring manometer was used to mea- 

 sure the blood-pressure instead of the ordinary mercurial manometer. This, 

 by recording each heart-beat on the tracing, enabled the rate to be accu- 

 ratelv determined. It was found that there was no increase, but in rabbits 

 the rate is already so high that one could hardly expect much change. 



A curious periodicity in the heart's action was observed in spme cases 

 towards the end of the experiment when the animal was dying, one or two 

 beats being missed at each inspiration. The explanation of this was not 

 at first clear, but in a subsequent experiment on a cat (Exp. 153), where 

 the heart was auscultated as the animal was dying and breathing in the 

 way shown in the tracing, it was noticed that towards the end of each in- 

 spiration the heart missed two or three beats. The explanation of this 

 seemed to be that as the respirations were infrequent and deep, and the 

 respiratory passages obstructed by quantities of mucus and saliva, the 

 deep forcible inspiration created so much negative pressure in the thorax 

 that the heart was unable to beat until the pressure was relieved by expira- 

 tion. That the variation was due to respiratory influence, and not to any 

 action of the drug upon the circulation, was shown in the case of this cat 

 by the fact that when respiration had ceased the heart continued to beat 

 regularly for two minutes and a quarter. 



With regard to Christie's statement that the arterioles are contracted, 

 no direct experiments were made, but some perfusion experiments on frogs 

 showed that there was no marked or constant change. Further, the 

 action on the heart is sufficient to account for the rise in blood-pressure. 

 Were the arterioles also constricted, one would expect a much higher rise 

 than occurs. Any influence that tutin does exert on the calibre of vessels 

 is exerted through the vaso-motor centre in the medulla, as seen in the 

 Traube-Hering curve already mentioned. 



Action on the Respiratory System. — The rate and amplitude of the 

 respiratory movement is markedly increased by tutin. After the first 

 injection in the anaesthetised animal the rate may be doubled. During 

 convulsive seizures the spasm of the respiratory muscles is very marked, 

 and respiration appears to be brought to a complete standstill — e.g., in a 

 cat (Exp. 3), during an interval of four minutes and a half, no visible or 

 audible sign of breathing could be noticed. Doubtless this is a frequent 

 cause of death in animals poisoned by a large absorption of tutin. 



That respiration ceases before the heart was a constant observation. 

 It was seen in fishes and in all animals where such an observation could be 

 made. 



