Indirect induction of vascular damage by x-irradiation.

T HE increased vascular permeability and hemorrhagic defects which have been observed following total body irradiation have been attributed to many causes. Cronkite et al. 1>2 correlated these changes with the well demonstrated thromboeytopenia 3 which occurs a few clays after exposure to whole-body ionizing radiation. However, there are a considerable number of reports which suggest that the etiology of these vascular changes might be attributed to one or more of the following: (1) direct damage to the vascular endothelium and perivascular connective tissue; 4 '"' (2) hypoprothrombinemia; 8 (3) a decrease in the concentration of circulating flbrinogen and damage to the reticuloendothelial system ; 7 (4) an increase in circulating histamine; 8 ' 9 (5) the destruction of mast cells and hyperhepa-rinemia; (6) the release of some yet uncharac-terized anticoagulant; 10 ' 11 and (7) vasodila-tion, 12 which would increase the tension on the walls of the vessels, thus increasing permea-bility and vascular fragility. All may be im-• plicated as contributory factors acting either independently or synergistically in the post-irradiation vascular syndrome. The present studies were undertaken to clarify, if possible, the role of humoral factors in the pathogenesis of vascular disturbances following total body irradiation. Methods Golden hamsters (Mesocrieetns auraiits) were anesthetized with an intraperitoneal injection of sodium pentobarbital (10 mg./lOO Gin. body weight). Both cheek pouches were everted and pinned out. One pouch was then shielded with a lead cover (8 mm. thick) and an area (500 mm. 2) of the abdomen was also shielded with the same material. Each animal was given 1,000 roentgens whole body x-irradiation of the following characteristics : 145 Kr, 6.5 ma., 0.5 mm. aluminum filter inherent in the tube, 30 cm., 35 y/minute. The moccasin (Agkistrodon piscivorus) venom test of Fulton et al. 13 was used to measure vascu-lar fragility by means of induced petcchial formation. In this test, anesthetized hamsters had both cheek pouches everted and pinned out to allow simultaneous tra.nsillumination and direct microscopic observation of the blood vessels of the pouch. Each pouch was then injected with 0.02 ml. of fresh 0.01 per cent moccasin venom dissolved in physiologic saline; petechial counts were made at %-hour intervals up to 1% hours, at which time the animals were returned to their cages. All tests were run on the fourth day after irradiation. These same animals were used again on the eighth postirradiation day to measure changes in dermal permeability …