90 PHYSIOLOGY OF MUSCLE AND NERVE 



activate it, and naturally, an excised muscle is more susceptible to 

 fatigue than a normal one, because it is quite unable to obtain new 

 material and to discharge the products of its metabolism. Likewise, 

 it may be inferred that a normal muscle is able to regain its functional 

 qualities within a relatively short time, while an excised muscle is not. 



This exhaustion, therefore, is referable to two causes, namely an 

 insufficient supply of nutrient material, inclusive of oxygen, and an 

 accumulation of depressing waste products. The fact that substances 

 of this kind are actually formed, needs no further substantiation, 

 because Ranke 1 has shown that the irritability of a fatigued muscle 

 may be restored by perfusing it with an ordinary non-nutritive solu- 

 tion, such as sodium chlorid. In addition, this investigator has 

 proved that the injection of extracts of the fatigued muscles of one 

 frog into the circulation of another gives rise to a typical depression 

 in the second animal. Inasmuch as these results can also be obtained 

 with solutions of lactic acid and creatin, he gave to these agents 

 the name of "fatigue substances," and later on included under this 

 term also carbon dioxid and acid potassium phosphate. (KH 2 PO 4 ). 

 More recently Mosso 2 has extended these experiments to warm-blooded 

 animals and has shown that the transfusion of the blood of a fatigued 

 dog into the circulatory channels of a second perfectly normal dog 

 produces in the latter most decided symptoms of fatigue. 



Weichardt 3 has attempted to add to the three fatigue substances 

 carbon dioxid, lactic acid and monopotassium phosphate, also a 

 certain specific muscle toxin which he calls kenotoxin. When isolated 

 from the other substances, this toxin, when injected into other animals, 

 is capable of producing the phenomena of fatigue. He also claims to 

 have obtained, by bacteriological methods, an antitoxin which serves 

 to counteract the effects of this toxin and to retain the muscle in a 

 reactive condition. These tests have more recently been repeated by 

 Lee and Aranowich, 4 but no evidence has been found to substantiate 

 the formation of an actual muscle toxin. 



It has also been shown by Lee 5 that small quantities of any of the 

 three fatigue substances previously mentioned, cause a temporary aug- 

 mentation in the activity of the muscle, as is evinced by an increase 

 in its irritability and working power. Thus, if a muscle is succes- 

 sively stimulated at intervals of, say, one second and its contractions 

 are registered upon a slowly revolving drum, the injection of a small 

 amount of any one of these agents temporarily increases the height 

 of these contractions. In this manner the curve may be made to show 

 periodic augmentations. This phenomenon is known as the " Treppe. " 

 In this connection it might also be mentioned that these staircase- 



1 Tetanus, Leipzig, 1865. 



2 Arch, de biolog. ital., xiii, 1890. 



3 Munchener med. Wochenschr., li, 1904, 12;lii, 1905, 1234; and liii, 1906, 1701. 



4 Proc. Exp. Soc. of Biology and Medicine, 1917. 

 8 Am. Jour, of Physiol., xx, 1908, 170. 



