40 



HANDBOOK OF PHYSIOLOGY 



CIRCULATION I 



from such data, as the time when the circulating label 

 has declined to one-half its initial value, corrections 

 being made for radioactive decay. Such studies 

 show that the half-life of proteins artificially labeled 

 with I'^' is considerably shorter than that of proteins 

 naturallv labeled with C" or S^^, and becomes 



progressively less as the iodination is increased (ii- 

 13, 151). The half-life of T-1824 dyed albumin is 

 less even than that of I'^' albumin (210). The inter- 

 pretation of such data is complicated, however, by 

 label reutilization after metabolic breakdown of the 

 labeled protein. There is no evidence for transfer of 

 dye to other circulating protein, and there seems to 

 be little retention of P'*' released by metabolic deg- 

 radation of iodinated protein (24). Even the natu- 

 rally incorporated labels C* and S'° have different 

 half-lives, due to differences in the rates of metabolic 

 degradation of the protein moieties containing them 

 (241). 



The requirements for metabolic studies, of course, 

 are much more rigorous than those for measurements 

 of plasma volume. A labeled protein is adequate for 

 the latter purpose if its initial distribution space 

 after circulatory mixing is the same as that of normal 

 plasma proteins. It is unfortunate for the present 

 purpo.ses that most studies comparing naturally and 

 artificially labeled proteins have been done with a 

 primary interest in metabolic history. Samples are 

 usually taken at such long intervals that it is impos- 

 sible to extrapolate the disappearance slope for the 

 first hour or two to an exact intercept in order to 

 compare initial distribution volumes. The reported 

 data permit a comparison of the total exchangeable 

 protein pools accessible to various labels, rather than 

 of the initial circulatory distributions (151). In the 

 few studies, however, in which attention has been 

 given to the initial distribution, no difference has 

 been found for proteins artificially labeled with 

 P'^ and those naturally labeled with C'^ or S'^ 

 (40, 65). 



Because of its commercial availability as prepared 

 radioiodinated human serum albumin, its convenient 

 radioactive half-life, and its ease of measurement, 

 I'" has been the most widely used radioactive plasma 

 label. Relatively few studies have been done on 

 species other than man with homologous iodinated 

 albumin (179, 242, 244). Still fewer have compared 

 heterologous and homologous albumins, and these 

 have failed to reveal a difference, so far as behavior 

 related to plasma volume measurement is concerned 

 (14, 237). Since dyed canine albumin and iodinated 

 human albumin have the same initial distribution 



volume in the dog, heterology seems to be of no 

 consequence in this species (210). 



The preparation of Ct^' proteins as suggested by 

 Gray & Sterling (88) in 1950 is technically much 

 simpler than the preparation of I"' proteins (120, 

 150, 165), and should facilitate studies with radio- 

 actively labeled autologous proteins. The only 

 reported studies with Cr^' as a plasma label, however, 

 have been done by injecting unbound Cr^'CU on 

 the assumption that protein binding would occur 

 within the circulation before appreciable loss had 

 occurred (72, 219). Insufficient data have been 

 reported with this technique to permit evaluation. 



Only scattered data on other radioactive plasma 

 labels are available. The report in abstract that 

 radioiodinated globulin has a smaller distribution 

 volume in man than T-1824 is puzzling (198). 

 It is in conflict with the documented report of identical 

 initial spaces for the dye and globulins in the dog 

 (90) and with data on the time required for albumins 

 and globulins to mix in the total exchangeable 

 protein pool (40, 151, 158). 



CELL L.-VBELS 



The first practical approach, in 1882, to measure- 

 ment of blood volume as a distribution space, made 

 use of carbon monoxide. Although it is a cell label, 

 and was selected by Grehant and Quinquaud because 

 of its affinity for hemoglobin, cell volume was not 

 calculated separately (see reference 64). Carbon 

 monoxide remained the only systematically employed 

 cell label throughout the period when dye methods 

 were being developed for plasma volume. When the 

 concentration of carbon monoxide was measured in 

 whole blood, and a value for total blood volume was 

 calculated, this usually agreed fairly well with the 

 value obtained by adding the dye distribution space 

 and Cl'h. Since a cell label and a plasma label thus 

 seemed to have the same distribution volume in 

 circulating whole blood, no need was apparent for 

 labeling both compartments and calculating them 

 separately (116, 201). 



It was not until other cell labels were introduced, 

 during the decade beginning in 1940, that the inade- 

 quacy of carbon monoxide as a cell tag began to 

 become apparent. Improved methods have been 

 developed for administering the gas and for measuring 

 its concentration (199). For clinical use, procedures 

 have been devised which obviate the need for drawing 

 blood samples, blood concentrations being calculated 



