THE REFRACTORY PERIOD AND FATIGUE 175 



stimulus. In other words, with the increasing deficiency of 

 oxygen, the response is not merely reduced for every stimulus, 

 but the duration of the refractory period is likewise progressively 

 prolonged until finally with an absolute want of ox3'^gen, constant 

 and complete depression takes place. In the genesis of this pro- 

 cess another factor, however, has the same effect. 



While with a sufficient supply of oxygen disintegration leads 

 to the formation of carbon dioxide and water, therefore to end 

 products, which can quickly and easily be removed by diffusion, 

 the want of oxygen produces complex products of incomplete 

 combustion and finally of anoxydative decomposition, such as 

 lactic acid, fatty acids and even more complex substances in con- 

 stantly increasing quantities. These products permeate the proto- 

 plasmic surfaces with great difficulty, if at all, and as they cannot 

 subsequently be oxydatively split up, constantly accumulate. 

 These asphyxiation substances, as they may be briefly termed, 

 produce a depressing effect on further disintegration. This can 

 be experimentally demonstrated. 



For this purpose I have modified the experiment previously 

 described in the way that after every introduction into the blood 

 of oxygen-free saline solution and after the injection of strych- 

 nine, the artificial circulation was stopped so that stagnation of 

 the oxygen-free saline solution took place in the vascular system. 

 The processes then occurred in exactly the same manner with 

 the exception that the state of non-irritability appeared somewhat 

 earlier. If after the beginning of complete depression artificial 

 circulation with oxygen-free saline solution was again started, a 

 certain degree of recovery took place within one or more minutes. 

 The stimuli were once more effective and produced a number 

 of contractions. At times, several single contractions, following 

 each other in more or less quick succession, could be brought 

 about. But complete recovery or the appearance of even incom- 

 plete tetanic convulsions was never again obtained, whereas by 

 the introduction of oxygen complete recovery could at once be 

 brought about. If, however, the circulation with oxygen-free 

 saline solution was continued, irritability gradually decreased. 

 The refractory periods after the individual stimuli became longer, 



