PHYSIOLOGY OF RADIATION INJURY 967 



in animals which vary in susceptibility, being more generalized in the 

 dog than in the rat (Allen et al, 1948; Kohn and Robinett, 1948). In the 

 dog, localized hemorrhages in the terminal state sometimes give rise to 

 myocardial and neurological signs (Prosser, Painter, Lisco, et al, 1947). 



Exposure to ionizing radiation may result in a decreased coagulability 

 of whole blood in animals and in human beings (Prosser, Painter, Lisco, 

 et al, 1947; Allen et al, 1948; Field and Rekers, 1949a; Silverman, 1949). 

 Allen and his associates (Allen and Jacobson, 1947; Allen et al, 1948; 

 Jacobson, Marks, Gaston, Allen, and Block, 1948) have observed a 

 prolongation of clotting time in acutely irradiated dogs which is related 

 to the appearance of a circulating heparin-like substance. The hemor- 

 rhagic diathesis in dogs is considered to be a consequence, for the most 

 part, of the circulating heparin-like material, since various antiheparin 

 substances, e.g., toluidine blue and protamine, can restore coagulability to 

 normal values and prevent hemorrhage even in the presence of thrombo- 

 cytopenia. The coagulation defect may occur before significant reduc- 

 tion of the blood platelets and in the absence of any change in pro- 

 thrombin time and in blood calcium and fibrinogen. It is not altered 

 significantly by transfusions of whole blood (Allen et al, 1951) or adminis- 

 tration of vitamins K or C. A similar clotting defect has been described 

 in rabbits (Jacobson, Marks, Gaston, Allen, and Block, 1948) and in man 

 (T. R. Smith et al, 1948) after treatment with nitrogen mustards. The 

 origin of the heparin-like substance is unknown; although it could arise 

 from mast cells, the exact role of these cells after irradiation is uncertain 

 (Kelsall and Crabb, 1952). It is of interest that chronic irradiation with 

 low dosages, although sufficient to result in blood damage and death, does 

 not appreciably alter blood clotting (Jacobson, Marks, and Lorenz, 1949). 



While the influence of toluidine blue or protamine on the development 

 and disappearance of radiation hemorrhage is dramatic, these agents do 

 not alter total survival appreciably. It is noteworthy that the median 

 lethal dosage for the rat can be reduced to that for the dog by injecting 

 heparin after irradiation (Kohn and Robinett, 1948) ; yet, the distribution 

 of hemorrhage in the heparinized irradiated rat is apparently unchanged 

 despite the increase in bleeding. This may imply a difference between 

 the rat and dog in the latent injuries that require "heparin-like sub- 

 stances" for their development; it should also be recalled that the hemor- 

 rhagic picture in traumatic shock varies greatly from species to species. 

 As contrasted with these observations, heparinization is said to decrease 

 the lung damage that appears in rabbits following repeated irradiation of 

 the thorax over a two- week period (Boys and Harris, 1943). Dicumarol 

 has also been employed to decrease pulmonary changes in man after local 

 irradiation (Macht and Perlberg, 1950). In this case the role of vascular 

 thrombosis in local tissue radiation damage may provide the explanation. 



The existence of a circulating anticoagulant is questioned by some 



