THE REFRACTORY PERIOD AND FATIGUE 173 



until finally irritability does not reappear at all, and even the 

 strongest stimuli fail to produce the least contraction. The 

 continuous manner in which the refractory period is, in the 

 absence of oxygen, more and more prolonged until eventually a 

 prolonged state of nonirritability is developed, can be better 

 followed by observing the experiment than when described in 

 words. If at this stage instead of the oxygen-free saline solution, 

 defibered blood of the ox shaken in air or a saline solution satu- 

 rated with oxygen is circulated in the frog, restitution is often 

 within a few minutes so complete that tetanic attacks are once 

 more produced by a single stimulus, that is, the refractory period 

 has from being practically nil returned to the normal. This 

 experiment can be repeated several times on the same animal. 

 It is invariably found that the refractory period is prolonged 

 by the withdrawal of oxygen and shortened with a renewed 

 supply. 



I have described this experiment somewhat in detail as it con- 

 tains facts which are the key for the comprehension of a general 

 physiological process of paramount importance. I refer to 

 fatigue. The refractory period and fatigue are inseparably con- 

 nected, for fatigue is founded on the existence of the refractory 

 period and is an expression of prolongation of the former, brought 

 about by want of oxygen. This is shown at once by closer 

 analysis. It is here necessary to differentiate somewhat more in 

 detail the factors which bring about the prolongation of the 

 refractory period in deficiency of oxygen. 



If we first turn our attention to the normal refractory period 

 which occurs in a system in metabolic equilibrium of rest in 

 direct connection with dissimilatory excitation, following a 

 momentary stimulus, we find that reduction of irritability or, 

 more exactly expressed, the lessening of the response is, as we 

 have seen, determined by the time involved in the metabolic 

 decomposition and recovery. Both these processes require time 

 and until their completion the quantity of substance demanded 

 for the oxydative disintegration is decreased in a given space, 

 and every stimulus must consequently be followed by a weaker 

 response. Our conceptions of the physical details of these pro- 



