Abstract
1. The minimum lethal dose of the dried venom of Crotalus adamanteus has been determined for white rats to be 0.025 gram of dried venom per kilogram when given intraperitoneally. This is about ten times the dose per kilogram necessary to kill a guinea pig and six times that for a rabbit.
2. Crotalus venom shows neither a tissue fibrinogen nor a thrombin clotting action on citrated horse plasma; and is a powerful anticoagulant in vitro.
3. The venom has a marked specific, proteolytic action on blood fibrinogen, which it converts into a more soluble protein coagulable at 82°C. and an albumose.
4. The venom has little or no proteolytic action on serum albumin or serum globulin, or on fibrin. Crotalus venom contains a protease which appears to be specific for a single protein, fibrinogen.
5. The venom has a lipolytic action on cephalin, liberating a fatty acid and destroying the power of the cephalin to form thrombin by union with calcium and serozyme.
6. The venom destroys, to some extent, the power of tissue fibrinogen to cause intravascular clotting, when both are injected in a mixture. Fibrinogen disappears from the blood even though no clots are found.
7. The fact that large doses cause clotting in vivo indicates that the venom has a weak thrombin action, but why this appears only in vivo and not in vitro remains to be investigated.
8. If a small dose of tissue fibrinogen, which is itself non-toxic, be injected intraperitoneally simultaneously with the injection of venom or a half hour before it, then a white rat is killed by a dose of venom from one-half to one-fourth of the minimum fatal dose when the venom is injected alone. The cause of this increased toxicity of the venom due to the action of tissue fibrinogen is being further investigated.
Footnotes
- Received November 14, 1929.
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