70 THE PHYSIOLOGY OF MUSCLE AND NERVE. 



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 the}^ con- 

 sist of the known products of muscular metabolism, namely, lactic 

 acid (or the lactates), carbon dioxid, and possibly also acid potas- 

 sium phosphate (KH2PO4). These results have been confirmed by 

 other observers,* and we may accept, therefore, the view that the 

 products of muscular activity, if they are allowed to accumulate in 

 the muscle, serve to diminish or suppress its contractihty, 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 prod- 

 ucts does actually occur. It is possible, of course, that other 

 intermediary substances are formed which may have a similar effect. 

 At present we are justified only in laying emphasis upon the known 

 products of muscular metabohsm, particularly the lactic acid. 

 When this substance 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 respira- 

 tory movements and upon the heart-rate is explained, as we shall 

 see, in a similar way. It should be added that Lee,t 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 influence 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 irrital)ihty if given a short 

 rest. But even in the case of a muscle in the body, with its cir- 

 culation intact, an interval of some hours is required before it re- 

 gains entirely its power to perform a normal amount of work. It 

 seems probable that the diminution in the total work-power of a 

 muscle after exercise is due to the fact that the supply of energy- 



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

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



t For discussion and experiments, see Lee, Harvey Lectures, 1905-08, 

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

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



