VOLUME OF BLOOD 



39 



when they are injected as a mixture (73), may account 

 for the differences wliich have occasionally been 

 reported for these two species (16, 17, 133, 227). 

 In some other species, however, there seems little 

 doubt that T-1824 has a consistently larger distribu- 

 tion volume than radioiodinated albumin. This has 

 been reported for the rabbit (242, 244) and for the 

 mouse (242). Comparative values are not available 

 for the rat. They might throw light on the widely 

 varying T-1824 distribution volumes reported by 

 different investigators for this species. These vary 

 from a low of 27.3 ml per kg (148) to a high of about 

 40 ml per kg (155, 236). 



Comparative studies with a variety of plasma 

 labels are needed in other species, in view of demon- 

 strated species differences. They are also needed in 

 man and in the dog under abnormal conditions. The 

 dye T-1824, along with others such as Congo red, 

 disappears at very fast rates in human subjects with 

 amyloidosis, with improbably large initial distribution 

 spaces in the neighborhood of 100 ml per kg (232). 

 In congestive heart failure it is still not clear whether 

 the enlargement of plasma volume is as great as it is 

 made to appear by T-1824, or whether this is in 

 part due to abnormal dye distribution. Blood volume 

 appears to be increased in this condition when it is 

 estimated with T-1824 as the only label, but not 

 when it is estimated with P'- (202, 203). The error 

 in such estimates has already been discussed. The 

 magnitude of the error, especially when attempts are 

 made to correct H, to H„, is likely to be greater in 

 those abnormal states in which precise knowledge of 

 blood volume would be of the greatest value. When 

 both cells and plasma are labeled, the distribution 

 volumes of both are found to be increased in con- 

 gestive failure, and the ratio mean circulatory hema- 

 tocrit '.central hematocrit reduced (207). Although 

 it is clear that other plasma labels such as radioiodi- 

 nated albumin have an expanded distriijution in this 

 condition, it is not clear, in the ab-sence of compara- 

 tive data, whether the expansion is the same as it is 

 for dye (207). 



An attempt was made in our laboratory a number 

 of years ago to compare, in acutely splenectomized 

 dogs, the distribution space of T-1824 with that of 

 undyed albumin, by using equation 2 as explained 

 in the introduction to this chapter (142). When these 

 studies were repeated recently on intact dogs, using 

 a continuous exchange to replace dyed circulating 

 plasma with undyed plasma without disturbing 

 arterial pressure, the dye and the undyed plasma 

 which replaced it seemed to have the same distribu- 



tion volume (fig. 2). Although such studips throw no 

 light on the anatomical distribution of the dye, it is 

 clear that any dye which may have escaped from 

 circulating plasma in normal dogs is freely exchange- 

 able with it. 



Other Dyes 



A red dye resembling the original Rowntree dye 

 but with better controlled composition, and known 

 as brilliant vital red, was introduced in 1920 (115). 

 In its early circulatory behavior it is indistinguishable 

 from T-1824 (56; 182). A number of other blue dyes 

 have been used by European workers (see ref 95). 

 The composition of T-1824 from readily available 

 sources is more carefully standardized than that of 

 most dyes, and more is known about its physiological 

 behaxior, spectral characteristics in plasma, and 

 protein binding. There is little reason to believe 

 that search for a superior dye label for plasma would 

 be worthwhile. 



Dves which are rapidly cleared from plasma by 

 hepatic, renal or other special excretory mechanisms 

 were discarded by Dawson el al. (50) as being unsuited 

 for plasma volume measurement. If unobserved 

 disappearance rates during the mixing period are 

 proportional to the observed rates for the post- 

 mixing period, present methods of correcting for loss 

 during the mixing period should be inadequate for 

 reasons that were stated earlier. It is difficult to 

 reconcile with these considerations a report that 

 rose Bengal, which has a disappearance rate of 50 

 per cent in 8 min in the dog, has the same distribution 

 volume as T-1824 (216). 



Plasma Proteins Labeled with Radioactive Tracers 



These were introduced by Seligman & Fine (70, 

 71, 211) in 1943. It is now possible to label albumins 

 or globulins in vitro with P''" or Cr^'; or in vivo by 

 administering tracer-laijeled amino acids to donors. 

 The tracers most commonly employed in vivo are 

 C" and S^^, and since they become metabolically 

 incorporated in plasma proteins, there is every 

 reason to believe that the labeled proteins follow 

 completely normal metabolic pathways. There is, 

 on the other hand, no reason to believe that artificially 

 labeled proteins, whether the label is a dye, V^^, 

 or Cr°', will have a normal metabolic history. For 

 metabolic studies, the disappearance of protein 

 label from plasma is followed for a period of days or 

 weeks, and the biological half-life is usually computed 



