CREATINE AND CREATININE 75 



varies from species to species, but is very constant in the individuals 

 of the same species ; those species with muscles richest in creatine 

 show also the greatest output of creatinine in the urine. The con- 

 stancy of content of muscle and of creatinine output would thus be 

 the expression of a dynamic equilibrium. 



The question whether creatine is formed as the result of muscular 

 work has been answered in the negative. 



Liebig found ten times as much creatine in the muscles of a fox 

 killed in the chase as in the captive animal, but Voit [1868] found 

 no increase after work or after tetanising. Van Hoogenhuyze and 

 Verploegh [1905 ; consult this paper for the earlier literature] only 

 found an increase when muscular work was done during absolute fast- 

 ing. Mellanby [1908], Scaffidi [1913] and others have also failed to 

 change the creatine content of muscle by work ; Brown and Cathcart 

 [1909] observed a slight increase after stimulation, but only with 

 isolated frog's muscles. 



Although creatine formation is not a function of rapid muscular 

 contractions, Shaffer [1908] regarded the creatinine output per kilo, as 

 directly parallel to muscular development or strength (" muscular 

 efficiency "), and Pekelharing and his pupils have during the last few 

 years connected creatine formation and creatinine output with muscu- 

 lar tonus. Weber [1908] had already shown that the surviving 

 pulsating heart, perfused with Ringer's solution, gave off creatine to 

 the perfusion fluid, and this observation was confirmed by Howell and 

 Duke [1908]. Weber also found that in the dog an increased crea- 

 tinine excretion could be induced by cinchonine convulsions (which 

 increase the tonus) but not by work ; the creatine in the muscles 

 decreased. Pekelharing and van Hoogenhuyze [1909, 1911] then 

 developed a new theory as to the effect of tonus on creatine formation. 

 They also observed a slight increase of the creatine content of muscle 

 during rigor ; the additional creatine is excreted in the urine as crea- 

 tinine. Pekelharing [1911] showed that there is an increase of urinary 

 creatinine after standing at attention for some hours in a military 

 position, but not after a long march. During sleep van Hoogenhuyze 

 and Verploegh [1905] had previously observed a decrease in the crea- 

 tinine output, which may be connected with the diminished tonus. 

 Beker [1913] has also supported this theory; he found that in preg- 

 nancy the creatine content of the uterus increases in the cow from 

 0-038 per cent, (calculated as creatinine) to 0*084 P er cent - m tne 

 gravid and 0-060 per cent, in the non-gravid horn. For pregnant and 

 non-pregnant human uteri the figures were 0*0766 and 0-0446 respec- 



