THE CHEMISTRY OF MUSCLE. 71 



tivity 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 simi- 

 lar effect. Thus Weichardt* has stated that muscular con- 

 tractions 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 

 in walking or climbing, may diminish the amount of work obtainable 

 from other unused muscles, such as those of the arms. So also the 

 effect of muscular exercise upon the rate of the respiratory move- 

 ments and upon the heart-rate is explained, as we shall see, in a 

 similar way. It should be added that Lee,f confirming an older 

 observation by Ranke, has published experiments which indicate 

 that the first effect of the so-called fatigue substances is to increase 

 the irritability of the muscle, while the later effect is to diminish the 

 irritability or to suppress it altogether. In this initial favoring in- 

 fluence Lee finds an explanation of the phenomenon of Treppe (see 

 p. 35). After the appearance of complete fatigue a muscle shows 

 usually some return of irritability if given a short rest. But even in 

 the case of a muscle in the body, with its circulation intact, an 

 interval of some hours is required before it regains entirely its power 

 to perform a normal amount of work. It seems probable that the 

 loss of power to do work is referable in part to a using up of the 

 supply of energy-yielding material, but the accumulation of the 



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

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



f For discussion and experiments, see Lee, Harvey Lectures, 1905-06, 

 Philadelphia, 1906; also "Journal of the American Medical Association," May 

 19, 1906, "American Journal of Physiology," 18, 267, 1907. 



