THE CHEMISTRY OF MUSCLE. 67 



becomes completely unirritable. We may define fatigue, there- 

 fore, as a more or less complete loss of irritability and contractility 

 brought on by functional activity. But even when the fatigue is 

 complete and the muscle fails to respond at all to maximal 

 stimulation, a very short interval of rest is sufficient to bring about 

 some return of irritability. For a complete restoration to its 

 normal condition a long interval of time may be necessary. If 

 the muscle is isolated from the body and thus deprived of its cir- 

 culation the recovery from fatigue is less rapid and less complete 

 than under normal conditions. In such an isolated muscle, more- 

 over, if provision is made to irrigate its blood-vessels with a solution 

 of physiological saline (Nad, 0.7 per cent.) the recovery from fatigue 

 is hastened. These facts seem to indicate clearly that fatigue is 

 not due to a complete consumption of the material in the muscle 

 that supplies the energy for the contractions. In other words, 

 fatigue as it usually presents itself to us in life or under experi- 

 mental conditions is a phenomenon different from exhaustion. 

 Ranke,* who made the first complete study of this subject, was 

 convinced that a muscle when tetanized to the point of complete 

 fatigue consumes only a fraction of the oxidizable or energy-yielding 

 material contained in its substance. He believed that there exists 

 in the fatigued muscle a something brought into existence by the 

 contraction itself, which retards or prevents further physiological 

 oxidation. In support of this view he found that if an extract 

 was made from the fatigued muscles of one frog and injected into 

 the circulation of a second frog, the muscles of this latter animal 

 gave evidence of fatigue, that is, they showed diminished power 

 of contraction upon stimulation. A similar experiment made with 

 an extract from resting muscle gave no such effect. Investigation 

 of the separate products formed in a muscle during contraction 

 demonstrated that the acid-reacting substances, sarcolactic acid 

 and acid potassium phosphate, are apparently responsible for this 

 effect. According to these experiments, the accumulation of these 

 acid products is responsible for the appearance of fatigue; the 

 muscle's own waste products, therefore, serve to limit its responsive- 

 ness to stimulation, and thus form a protective mechanism that 

 saves it from complete exhaustion. Under normal conditions these 

 products are quickly removed by the blood, and even in the isolated 

 muscle we may suppose that their depressing effect upon the irri- 

 tability of the muscle is rapidly removed by the neutralizing effect 

 of the alkaline lymph in the muscle; perhaps, also, the lactic acid 

 is further oxidized. This chemical theory of fatigue does not, how- 

 ever, explain all the phenomena, particularly the after-results. 

 As was stated in describing the experiments made with the ergograph, 

 * Ranke, " Tetanus," Leipzig, 1865. 



