PRINCIPLES OF TRACER METHODOLOGY 35 



Further relationships in regard to the rate of transfer to the individual 

 areas A and B and detailed derivations may be found in the original paper 

 (75). Equation (1-32) is expressed in terms of concentration of labeled 

 Na. For purposes of comparison it is convenient to express the con- 

 stants Cp, Ceq, oi, and ao in terms of fractions of the initial labeled Na con- 

 centration, and the eciuation then becomes 



Cp - 0.247 = 0.522e-' """ + 0.231f?-« ««»' (l-32a) 



It is necessary to consider the physiological interpretations possible 

 from this type of information. It is clear that the dynamic state of the 

 various constituents in the body system can be quantitated as far as 

 removal and reentry into plasma are concerned. Although these curves 

 do show one or more characteristic transfer rates, it is recognized that 

 they represent the results of complex processes that cannot be mechanis- 

 tically interpreted at this time. 



In general, there are several possible processes that could account for 

 removal from the plasma at more than one rate. For example, the sub- 

 stance might be present in the plasma in more than one form, each of 

 which might be removed at its characteristic rate, or the substance might 

 pass across the vascular membrane at a different rate than that of the sub- 

 sequent passage across the cell membrane. On the basis of other obser- 

 vations, it has been suggested that at least Na and K are transported 

 across the capillary wall at different rates in different parts of the system. 

 Thus, on the basis of tissue accumulation of injected labeled sodium, 

 Gellhorn et al. (75) consider that sodium ions in the extravascular system 

 may be divided into two groups, one group being in areas where the rate 

 of exchange with plasma ions is relatively rapid and the other group 

 being in areas where the rate is relatively slow. 



Obviously, much more information is needed on the kinetics of accu- 

 mulation in the various compartments. Subjectively one thinks of the 

 rapid rates of removal as being concerned with mechanical mixing and 

 physical processes such as fixation to proteins and cell surfaces. Shep- 

 pard et al. (76) have studied theoretically and experimentally the mixing 

 of K^'- in the plasma, a process that was shown to be predominantly 

 oscillatory. The next slower rate would probably be concerned with 

 diffusion or filtration into tissues and cells. The slowest rates may rep- 

 resent excretion. 



Uncertainties in the method may arise from the existence of removal 

 rates of similar magnitude which therefore cannot be resolved. It has 

 also been pointed out that the mean capillary concentration of an injected 

 substance may not equal that of the arterial blood until some time after 

 injection (77). However, this does not seem to be an important factor in 

 the normal intact animal. 



