THE METABOLISM OF PROTEIN 653 



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 in the investigation 

 of problems of metabolism should always ~be very carefully controlled and 

 the results should never constitute the only evidence upon which impor- 

 tant conclusions are based. 



(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 throwing 

 light on such problems as that under consideration namely, the examina- 

 tion of the inflowing and outflowing blood of different parts or organs is 

 not applicable in most cases. This is because of the extremely small 

 changes in concentration which may occur even although large amounts 

 of the particular substance in question are being absorbed or produced. 

 As we shall see later, this criticism is particularly applicable in the case 

 of sugar. Even during the injection of considerable quantities of sugar 

 into the portal vein, no difference in percentage can be demonstrated 



