70 THE PHYSIOLOGY OF MUSCLE AND NERVE. 



to whom we owe the first thorough investigation of this subject, 

 was led to believe that as a result of the chemical changes occur- 

 ring in the muscle during contraction certain substances are 

 formed which depress or inhibit the power of contraction. In 

 support of this view he found that extracts made from the 

 fatigued muscles of one frog when injected into the circulation 

 of another fresh frog would bring on the appearance of fatigue 

 in the latter. Control experiments made with extracts of 

 unfatigued muscles gave no such result. He designated these 

 inhibitory products as fatigue substances and made experiments 

 to prove that they consist of the known products of muscular 

 metabolism, namely, lactic acid (or the lactates), carbon dioxid, 

 and possibly also acid potassium phosphate (KH 2 PO 4 ). These 

 results have been confirmed by other observers,* and we may ac- 

 cept, therefore, the view that the products of muscular activity, 

 if they are allowed to accumulate in the muscle, serve to diminish 

 or suppress its contractility, and, in all probability, this effect is due 

 to the acidity of the products formed (lactic acid, carbon dioxid). 

 We know' that when muscular activity is prolonged, or is carried 

 out under conditions which imply a lessened supply of oxygen, an 

 accumulation of some of these products does actually occur. It is 

 possible, of course, that other intermediary substances are formed 

 which may have a similar effect. Thus Weichardt f has stated that 

 muscular contractions give rise to a definite toxin, derived from the 

 protein material of the muscle, which, in his opinion, is the chief 

 agent in causing fatigue. He claims to have isolated this fatigue 

 toxin (kenotoxin) to the extent at least of having freed it from 

 the above-mentioned fatigue substances of Ranke. When 

 injected into the circulation of a fresh animal, it brings on fatigue 

 or even death. Moreover, by injecting it in suitable doses, the 

 body may form an antitoxin, and this latter substance, when given 

 to a fresh animal, may confer upon it an unusual capacity for 

 performing muscular work. It is not advisable, however, to 

 accept these statements until the facts have been corroborated 

 by other observers and further experiments. At present we are 

 justified only in laying emphasis upon the known products of mus- 

 cular metabolism, particularly the lactic acid. When this sub- 

 stance accumulates in the muscle it may be carried off in the 

 blood and thus influence other organs. On such a supposition we 

 may explain the fact, brought out by ergographic experiments, that 

 marked exercise of one set of muscles, for example, those of the legs 



*Lee, "American Journal of Physiology," 1907, 20, 170, and Burridge, 

 "Journal of Physiology," 1911, 41, 285. 



t Weichardt, "Archiv f. Anat. u. Physiol. (physiol. Abth.)," 1905, 219; 

 also"Miinchener med. Wochenschrift," 1904, 1905, 1906. 



