HA MORRHAGINS OF SNAKE VENOM 161 
HISTOLOGICAL CHANGES CAUSED BY VENOM HA2MORRHAGINS. 
In endeavoring to discover the precise mode of the action of heemorrhagin 
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 hemorrhage, 
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 hematoxylin 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 hemorrhages 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 hemorrhage. 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 hemorrhagin, 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.” 
