140 VENOMOUS SNAKES AND THE PHENOMENA OF THEIR VENOMS 



guinea-pig's blood, the blood becomes black and forms no coagulation, while 

 0.005 gm. produced a black clot after one hour, and no serum separated 

 when examined the next day. The quantities of 0.0025 &^- ^^^ 0.00125 

 gm. in I c.c. of saline solution and mixed with i c.c. of guinea-pig blood 

 retarded coagulation only a few minutes or about 10 minutes, and ren- 

 dered the color of the clot very black, no serum exuding from it the next 

 day. It is interesting to see that throughout the entire experiment, while 

 saline-isotonic solution without venom required 6 minutes for coagulation, 

 the mixtures containing 0.000625 gm., 0.000312 gm.,and 0.00007 g^- produced 

 coagulation in 2 minutes and a red-stained serum separated out. The clots 

 in these tubes became semi-fluid the next day. The quantities of 0.000028 

 gm. and 0.000004 gm. allowed the blood to form a bright red clot, from which 

 stained serum was separated out when examined the next day. 0.000002 gm. 

 in I c.c. mixed with i c.c. of the blood did not exert any influence in regard 

 to coagulation and subsequent serum exudation, which was exactly the same 

 as with the control. 



Using the doses of from 0.0002 to o.oooi gm. of cobra venom per i c.c. of 

 the blood, they have demonstrated the specific anti-inhibitory property of 

 Calmette's antivenin upon this venom. Their conclusions are: 



(i) Cobra venom delays or inhibits the clotting of the blood in vitro. 



(2) This inhibitory action is neutralized by antivenomous serum in vitro. 



(3) This action of antivenomous serum in vitro is specific. 



(4) Antivenomous serum itself, when added to blood, delays clotting. 



(5) For a certain dose (0.0001 gm.), the measure of the neutralization in 

 vitro, using clotting as a test reaction, is also the measure of the neutralization 

 in corpore for guinea-pigs. 



(6) The neutrahzation of the toxin by its antitoxin, in vitro, is certainly not 

 vital nor cellular, but must be chemical. 



Lamb and Hunter were able to show that the injection of a large amount 

 of cobra venom into a vein of rabbit never produces intravascular throm- 

 bosis, but causes some deficiency of coagulability of the blood. The diminu- 

 tion of coagulability was found to be more pronounced the larger the amount 

 of venom injected. This fact seems to furnish an easy explanation why 

 Wall, who used a small quantity of the venom, failed to obtain diminished 

 coagulability, while Cunningham,^ who killed the animal in a few minutes 

 with a much larger amount of cobra venom, observed the loss of the clotting 

 power of the blood of the animal after its death. 



Here a most striking dift'erence in the physiological action of the cobra and 

 daboia venoms is brought to light. The former produces, if employed strong 

 enough, a state of diminished coagulabihty without producing any increased 

 clotting power, while the latter produces, if in larger quantities, a sudden 

 increase of coagulability, culminating in an instantaneous thrombosis in the 



I Kanthack and Cunningham both observed that the blood running into a strong solution of cobra venom 

 either remained permanently unclotted, or the clot which formed after considerable delay was 

 soft and gelatinous and no senam exuded. 



