Does a fatigue toxin exist?

Abstract

In 1904 Weichardt claimed to have found a specific substance, a fatigue toxin, as the chief agent in the production of fatigue. When present it was capable of forming in the tissues its own antidote, an antitoxin. A substance identical with fatigue toxin, named “kenotoxin,” was obtained in vitro by treating proteins in various ways. However obtained, the substance, when injected into animals in small quantity, resulted in the production of antitoxin; when in larger quantity, it caused a great reduction in bodily temperature, slowing of respiration, sleep, and ultimately death.

In the present experiments animals, such as rabbits or cats, were fatigued by running in a revolving wheel. After fatigue was pronounced the animals were killed by decapitation, and the muscles of the hind legs were stimulated directly by the faradic current until they ceased to contract. Soon after death, in some cases within six to eight minutes, marked rigor was observed in the skeletal musculature. Immediately after the cessation of response to faradic stimulation the muscles of the hind legs were removed, cut to pieces and ground thoroughly with sand, and the muscle juice was squeezed out by a powerful press, all procedures being carried on with aseptic precautions. The juice was found markedly acid to litmus. When this juice was injected into the peritoneal cavity of guinea pigs, usually in quantities as large as 10 c.c., either at the temperature of the room or after being warmed to bodily temperature, the animal became quiet; there was no constant effect on respiration, which sometimes increased in rate and sometimes decreased; and the bodily temperature began to fall at once. The fall continued during 30 minutes to I hour, the maximum so far observed being 1.6° C., after which there was a slower return toward the original temperature. These are the only immediate effects that have been observed. Occasionally the animal died on the following day. Precisely the same effects, including occasionally death on the next day, were obtained when the muscle juice of non-fatigued animals was used.