1904.] Pharmacology of Indian Cobra Venom. 



189 



The early fall is undoubtedly due to inhibition of the heart. It 

 has been clearly shown that this is mainly brought about by the direct 

 action of the poison on the vagal centres in the medulla oblongata, 

 as it occurs before the accompanying failure of respiration has had 

 time to act. Moreover, it is seen whilst artificial respiration is being 

 actively carried on, and can be checked under these circumstances by 

 division of the vagi. 



On the other hand, there can be no doubt that asphyxiation of the 

 vago-inhibitory centre intensifies and maintains the inhibition which 

 direct influence of the venom on the vagal centre produces. 



The spontaneous recovery of respiration, or the application of 

 artificial respiration, has a powerful influence in mitigating the action 

 of the venom on the vagal centre. In the same way artificial respira- 

 tion, and to a less extent the spontaneous recovery of respiration, 

 appear to act beneficially on the poisoned respiratory centre. 



Even if the heart is cut adrift from all central vagal impulses, 

 whether direct or indirect, by the division of the vagi, there yet 

 remains evidence of a continued inhibition which must be attributed 

 to the direct action of Cobra venom on the terminals of the vago- 

 inhibitory mechanism. This action would appear to be a direct one, 

 but there is every probability that it is indirect as well, in other words 

 that it acts through asphyxiation of the vagal terminals, as well as> 

 by the poisoning of these parts by the circulating poison. There is, 

 however, another factor which must not be lost sight of, viz., a direct 

 exhaustion of the heart muscle as the result of irregular over- 

 stimulation. 



2. When the secondary rise of blood pressure, which follows the 

 primary fall, occurs, it is due to the same factors which determine its- 

 occurrence when small closes have been injected. It remains to explain 

 why it is sometimes absent, brief or ill marked. The explanation is 

 simple ; it is merely a question of cardiac failure. We have seen that 

 the direct inhibitory action of the venom through the vagal centre is 

 capable of overcoming the tendency which the blood circulating, 

 through the heart muscle has to throw that muscle into death in 

 systolic tone. Were it not for these two rival forces to some extent 

 equilibrating each other, Cobra poison would kill by its direct action 

 on the heart muscle. When the doses are comparatively small, or 

 when the vagi are cut or thrown out of gear by atropine, we find the 

 tonic cardio-muscular influence of the venom in evidence, but when 

 the dose of venom is a large, and especially when it is intravenously 

 given (the vagi remaining intact), the inhibitory action overpowers the 

 muscular excitation, and failure of the heart occurs. If the inhibition 

 is sufficiently well marked, no amount of arteriolar spasm that occurs 

 will compensate it, consequently the blood pressure falls. 



When the dose of venom is a very large one, the direct muscular 



