PHYSIOLOGY OF RADIATION INJURY 979 



circulating Evans blue has been described in dogs by other investigators 

 (Prosser, Painter, and Swift, 1947) ; yet plasma albumin, to which Evans 

 blue is bound, is said to be diminished at the time of greatest reduction in 

 dye disappearance. An increase in the rate of dye disappearance might 

 be expected if the decline in albumin were due to its leakage through 

 capillaries with increased permeability to colloids. The discrepancy in 

 dye disappearance is not easily resolved ; in the dog experiments determin- 

 ations were made on the same animals at different postirradiation times, 

 whereas with mice and rabbits, single determinations were made on 

 paired control and irradiated animals. 



That augmented disappearance of various tagged substances in mice 

 and rabbits is indicative of increased permeability is perhaps strengthened 

 by the finding that macrophage function is not altered appreciably (Wish 

 et al., 1952; Barrow et al., 1949). Although colloidal gold leaves the 

 circulation more rapidly, the absolute amount that is retained in the 

 liver and spleen is essentially similar in both control and irradiated 

 animals. It is conceivable that the apparent increase in permeability 

 results, in part, from intravascular changes such as cell clumping and 

 platelet thrombi, which lead to stagnation and decrease in the effective 

 blood volume, although local anoxia and increased hydrostatic pressure 

 would favor leakage under these conditions. Since capillary obstruction 

 has been noted in in vivo preparations (Smith, Svihla, and Patt, 1951), it 

 is difficult to guess the extent to which heightened capillary permeability 

 is apparent or real and whether this is a direct or indirect result of the 

 action of radiation on the vascular endothelium. It should be pointed 

 out that there is no evidence for increased permeability of renal glomeruli 

 and, therefore, that altered permeability following irradiation is probably 

 not typical of capillary endothelium. 



Vascular fragility is thought to be increased after irradiation since 

 hemorrhage is not always related to the thrombocytopenia and delayed 

 clotting, and mild trauma frequently results in showers of petechiae 

 (Field and Rekers, 1949a). Increased fragility is suggested further by 

 the rapid disappearance of labeled erythrocytes from the circulation and 

 by the presence of blood in the lymph of X-rayed rats and dogs several 

 days postexposure (Bigelow et al., 1951; Wish et al., 1952). Bleeding 

 may be minimized, moreover, by certain of the flavonoids although this 

 has not been verified universally (Rekers and Field, 1948; Field and 

 Rekers, 1949a; Kohn, Robinett, and Cupp, 1948). Rutin is reported to 

 antagonize hyaluronidase (Beiler and Martin, 1947), but the enzyme 

 probably does not play a role in altered fragility. Other hyaluronidase 

 inhibitors fail to influence radiation toxicity (Field and Rekers, 1949b), 

 and hyaluronidase itself is inactivated by irradiation in vitro (Schoenberg 

 et al., 1950). It is, of course, possible that the relatively small dosages 

 of radiation that are required to induce bleeding result in direct degrada- 



