THE CHEMISTRY OF MUSCLE. 69 



contained myosin and myogen, spontaneously, or under the action 

 of acid products of metabolism, pass into their insoluble forms, 

 namely, myosin fibrin and myogen fibrin. 



2. There is an increased acidity due to a production of lactic 

 acid. 



3. There is a production of CO2. Much importance was 

 attributed formerly to this product in the belief that it indicated 

 the occurrence of a reaction similar to "that taking place in con- 

 traction. Fletcher and Brown* give proof, however, so far at least 

 as heat rigor and chloroform rigor are concerned, that the CO2 

 formed does not arise from a metabolic breakdown of organic 

 material, but is simply an indirect result of the production of acid. 

 This acid as it accumulates acts upon the carbonates in the muscle 

 and thus leads to a liberation of the CO2. The CO2 produced in 

 this manner has no physiological significance. If, however, the 

 muscle during the development of rigor is supplied plentifully with 

 oxygen, then the lactic acid, as it is formed, undergoes oxidation, 

 with the production of CO2. In the absence of oxygen, therefore, 

 CO2 is formed from the action of the lactic acid on the alkaline car- 

 bonates, while in the presence of oxygen an additional amount is 

 formed by oxidation of the lactic acid itself. 



4. The consumption of glycogen. According to recent ob- 

 servers, carbohydrate disappears during rigor as it does during 

 contraction, and the loss in carbohydrate runs parallel to the 

 increase in lactic acid.f 



The Relation of the Chemical Changes during Contraction 

 to Fatigue; Chemical Theory of Fatigue. — As we have seen, a 

 muscle kept in continuous contraction soon shows fatigue; it 

 relaxes more and more until it becomes completely unirritable. 

 We may define fatigue, therefore, 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 com- 

 plete restoration to its normal condition a long interval of time may 

 be necessary. If the muscle is isolated from the body and is thus 

 deprived of its circulation and its proper supply of oxygen, fatigue 

 appears more rapidly and is recovered from less completely. 

 Ranke,! to whom we owe the first thorough investigation of this 

 subject, was led to believe that as a result of the chemical changes 

 occurring in the muscle during contraction certain substances 

 are formed which depress or inhibit the power of contraction. In 



* Fletcher and Brown, "Journal of Physiology," 48, 177, 1914. 

 t Parnas and Wagner, "Biochem. Zeit.," 1914, 61, 387. 

 t Ranke, "Tetanus," Leipzig, 1865. 



