THE METABOLISM OF PROTEIN 619 



perfused, no urea is formed. The evidence shows that the liver is an 

 important seat of urea formation, but not necessarily that other organs 

 are unable to form it in the intact animal, for there are many sources 

 of inaccuracy in perfusion experiments. Even though we exercise the 

 greatest care, we can not hope to maintain the organ in other than a 

 slowly dying condition. It is certainly far removed from the normal 

 state, as is revealed not only by histological examination, but by the fact 

 that edema almost invariably sets in and the blood vessels become ex- 

 tremely constricted, thus necessitating a gradual increase in the. per- 

 fusion pressure as the perfusion goes on. Furthermore, the organ being 

 isolated from the nervous system, there can be no control of the rela- 

 tive blood supply of different parts. In the intact animal the circula- 

 tion is more or less distributed according to the particular needs of the 

 different viscera, and such conditions obviously can not be simulated in 

 a perfusion experiment. Another objection depends on the fact that 

 the well-being of the organs in the intact animal is largely dependent on 

 hormones conveyed to them from other organs. Such hormones are 

 frequently quite labile in nature, and soon disappear from the perfusion 

 fluid. 



Notwithstanding these objections, there can be no doubt that many 

 of the functions of an organ are retained much longer than they would 

 be if the organ were not perfused ; for example, the contractility of the 

 muscle or the power of forming urea in the liver. Perfusion experiments 

 are of value therefore when they yield positive results. Negative re- 

 sults may indicate either that the organ does not perform the particular 

 function that is being investigated or that it has lost this function as a 

 result of partial death. That a perfused muscle retains its power of 

 contraction does not necessarily indicate that it maintains all of its 

 metabolic functions; neither does the fact that the liver forms urea 

 prove that it is capable of performing its other functions. It is easy to 

 show that the liver dies piecemeal; some functions, such as glycogen- 

 formation, die early, while others, such as urea-formation, remain for a 

 long time intact. The use of perfusion experiments for the settling of 

 questions of metabolism should therefore always be very carefully con- 

 trolled and never used as the sole line of evidence on which to base impor- 

 tant conclusions. 



(3) Before leaving this subject it may be well to point out that the 

 method which at first sight might appear to be the simplest for settling such 

 questions namely, the examination of the inflowing and outflowing blood 

 of different parts or organs is not applicable in most cases. This is be- 

 cause of the extremely small changes in concentration which may occur 

 even although large amounts of the particular substance in question 



