HiEMORRHAGINS OF SNAKE VENOM 161 



HISTOLOGICAL CHANGES CAUSED BY VENOM RffiMORRHAGINS. 



In endeavoring to discover the precise mode of the action of hsemorrhagin 

 Flexner and Noguchi have resorted to the mesentery of guinea-pigs and 

 rabbits. The venom (Crotalus adamanteus) was injected into the peritoneal 

 cavity, or, following Weir Mitchell's method, a minute particle of the dried 

 venom was placed on the exposed mesentery. The areas of haemorrhage, 

 when in thin, transparent membrane, were spread over small bottle-tops, 

 carefully fastened with fine silk, excised, and hardened, usually in Zenker's 

 fluid. The staining was done in haematoxylin and eosin. The preparations are 

 transparent and perfectly adapted for the study of the vascular walls. Places 

 showing the smaller, incipient extravasations are suitable for close scrutiny. 



The changes in the vascular walls associated with haemorrhages are clear 

 and unmistakable. The extravasations take place, not by diapedesis, but 

 through actual rents in the walls. The explanation of the rents is of much 

 interest. That they are not simple ruptures seems to be proved by the dis- 

 appearance, as if through solution, of the parts of the wall at the point of 

 the escape of corpuscles. The solution of continuity is one-sided, and, in some 

 cases, is attended by a displacement of the adjacent endothelial cells, which are 

 pushed outward, away from the vessel, by the force of the escaping blood. 



Other phenomena have been noted. Among those of interest is the occur- 

 rence of stasis in vessels, attended, usually by haemorrhage. That the condi- 

 tion is stasis, with the disappearance of the cell-contours, and not agglutination 

 of corpuscles, is shown by the separate state of the red cells beside the vessels 

 in the rare cases of associated stasis and extravasations. (Plate 27, A, b, c.) 



Giant cells occur in the course of the vessels in which venom changes are 

 going on. They are fusion giant cells arising from intravascular leucocytes. 

 From their size they must almost, or completely, block smaller veins in which 

 they form. 



The escape of corpuscles is not limited to the red cells. White cells also 

 pass out. Where the latter are noticeable, they are in far greater relative 

 proportion than in the circulating blood. The manner of their escape, 

 namely, by emigration, is easily followed. But especially interesting is the 

 fact that while, in some areas of specimens, the polynuclear cells predominate, 

 in others the mononuclear are chiefly met with. 



The escape of corpuscles by dissolution of the walls of the vessels is limited 

 to capillaries and small veins. When acted upon by venom both show irregu- 

 lar bulging of the walls, with which enlargements extravasation is often con- 

 nected. It is probable that the points of contact with venom, and of injury 

 of the vascular coat, are many, but only in a part of these does the vessel give 

 way entirely. 



In conclusion, Flexner and Noguchi made the following statement: "We 

 look upon haemorrhagin, therefore, in the light of a cytolysin for endothelial 

 cells of blood vessels, the destruction of which is the direct cause of the escape 

 of blood into the surrounding structures." 



