The comparative effects of total-body exposure to 60 Co gamma rays or fission spectrum neutrons on subcutaneous capillary blood flow in the ${\rm B}6{\rm CF}_{1}$ mouse have been estimated by measurement of xenon clearance after subcutaneous injection of ${}^{133}{\rm Xe}$ in a saline solution. These findings are important as an indicator of functional changes in the micro-vasculature that can then be related to structural changes observed both in vivo and with the electron microscope. The clearance of ${}^{133}{\rm Xe}$ from the subcutaneous injection site can be fitted to a single exponential. In unirradiated control mice, the mean halftime $(T_{{\textstyle\frac{1}{2}}}={\rm ln}\,2/\lambda)$ in 4-month-old animals was 9.83 ± 0.72 min and ranged between 9.48 and 10.70 min during the first 12 months of observation (4-16 months of age). The halftime increased to 130-140% of the initial mean value during the second year, and then decreased to as low as 50% in very old animals. In mice irradiated at 4 months, the clearance halftime of ${}^{133}{\rm Xe}$ increased significantly 3-6 months after exposure to gamma rays or fission neutrons at dose levels well below the acutely lethal range (e.g., 268 gamma rad or 80 neutron rad). More severe injury levels, but still below the acutely lethal range, resulted in little change from mean control values. In all irradiated groups, however, clearance times were shorter at ages in excess of the mean survival time, suggesting a compensatory increase in capillary blood flow. Although capillary blood flow showed significant changes in relation to radiation quality and dose, the absence of a clear dose-response relationship precludes quantitative comparison of dose effectiveness for neutrons and gamma rays.

The kinetics of injury accumulation during a single exposure to 60 Co γ-rays is described in the adult rooster and 3-wk chicken, and the results compared with those previously reported for the 3-day chick. Single exposure periods vary from 30 to 1440 min, with exposures in the lethal range for early (0-2 day) and for later (3-30 day) acute mortality. For early mortality, an empirical model based on a constant repair or reversal rate during irradiation describes the dose-time relations. Individual repair rates are assumed to be normally distributed and independent of exposure rate. In addition, there appears to be little influence of age between 3 days and 6 mo. For the later (3-30 day) mortality, repair or reversal processes operating during irradiation are time limited as well as rate limited, with an effective period of about 360 min. The effectiveness of dose protraction decreases with age.

White Leghorn roosters, 3-4 days after hatching, received single exposures to either 60 Co γ-rays or 200 kVp x-rays. Doses were in or immediately below the acute lethal range. Survivors at 35 days were caged individually and maintained for duration of life observations (85 control and 193 irradiated birds). Survival time, weight, and major pathologic findings were determined in control and in four irradiated groups (A, 24-hr γ-ray exposure to 700-1000 R, 30-day lethality <3%; B, 24-hr γ-ray exposure to 1200-2000 R, 30-day lethality 10-80%; C, 6-60 min γ-ray exposure to 700-1100 R, 30-day lethality 10-80%; D, 30-min x-ray exposure to 1000-1200 R, accompanied by prophylactic treatments that reduced acute lethality from 99% to 30-80%). Mean survival time of controls was about 6 years and maximum life span was 10.6 years. A single γ-ray exposure in the acute lethal range (groups B and C) resulted in a mean life shortening of about 50%, and the decrease in body weight (growth) was correlated with decrease in mean survival time. When the exposure time was increased from 1 hr to 24 hr, radiation effectiveness for life-span shortening and for weight was reduced. In x-irradiated birds protected against acute lethality by various prophylactic treatments, there was a differential effect on survival and growth; growth was more severely reduced than would be expected on the basis of 30-day mortality or life-span shortening. The principal radiation-induced lesions were those characteristic of cardiac failure; these were observed most frequently in birds that died before 5 years of age. Tumors were commonly testicular in origin; they were found with equal frequency in irradiated and unirradiated groups. The incidence of leukosis, a virus-induced neoplasia, was reduced in irradiated groups and was zero after the higher radiation exposures (groups B and D).

Early circulatory collapse in the lethally irradiated chicken, in which the vasculature is fully differentiated, is similar to that previously described in the chick embryo. Effects of whole-body 60 Co γ-irradiation in the 3-week chick are considered in relation to quantitative difference in early mortality (<24 hours) after short (15 minute) and protracted (24 hour) exposures. The microcirculation in the wing skin was studied before and for several hours after irradiation and observations were recorded cinemicrographically. Intravenously injected colloidal carbon was used to indicate areas of vascular damage. Stasis and occlusion of smaller superficial vessels occurred within 1 or 2 hours after a 15-minute exposure to 1200 R. Swollen endothelial cells and carbon accumulation in disrupted vessel walls were demonstrated in localized regions, especially in capillaries and venules, within 3 or 4 hours after exposure. Mortality exceeded 80% within 24 hours. When the radiation exposure was protracted over 24 hours, a dose of 10 000 R resulted in stasis and lysis of relatively few vessels and fewer than 5% of the chicks died within 24 hours after the exposure had been completed. Radiation injury resulted in a random distribution of microvascular damage sufficient to cause carbon labeling, in contrast to the more uniform pattern that has been observed after localized trauma (e.g., heat or crushing).

The early response to lethal doses of ionizing radiation in the chicken and chick embryo is characterized by rapid structural and functional changes in the vascular system. Increase in exposure time from a few minutes to a few hours has been shown to reduce the dose effectiveness for this injury mechanism. An x-ray exposure to 1100 R delivered in 12 minutes resulted in more than 95% mortality within 24 hours; when the exposure time was increased to 240 minutes, 1100 R represented a sublethal dose, 1800 R a 50% lethal dose, and 2200 R a 95% lethal dose. Effects of these exposures on the microcirculation were studied in the explanted chick embryo. The extent of injury to the vascular system could be correlated with the amount of lethality produced by the irradiation. A 240-minute exposure to 1100 R produced little effect on the microcirculation. Only after exposure to 2200 R was there a rapid circulatory collapse comparable to that produced by a 12-minute exposure to only 1100 R. Degenerative changes in individual endothelial cells appeared to be a direct effect, which was reduced when the exposure time was increased.

Exposure of the chicken and chick embryo to lethal levels of ionizing radiation results in a circulatory failure and early mortality (<24 hours). This injury response, previously characterized in relation to physical factors of the experiment (dose, dose rate, and time), involves a circulatory collapse that results from increased vascular permeability and degenerative changes of the vascular endothelium. These effects, leading to circulatory stasis and death, have been observed and recorded cinemicrographically in irradiated chick embryos. After 66 to 68 hours of incubation, embryos (including the entire area vasculosa) were explanted onto an agar-albumen medium and subjected to 250-kv X-ray exposures of 700 R or 1100 R, delivered in 12 minutes. These exposures resulted in 10% or 90% mortality, respectively, within 24 hours. Circulation in chick embryos exposed to 700 R was similar to that in nonirradiated controls. After exposure to 1100 R, the hemoconcentration observed within 30 to 45 minutes suggested a plasma loss. In localized areas circulating cells adhered to the endothelium, and thrombi formed. Vascular degeneration progressed until stasis became complete, frequently within 4 to 6 hours after exposure. A movie, illustrating these findings, is available upon request. Order movie by title and number: ANL-MP-730-153, Early changes in the microcirculation in the x-irradiated chick embryo. Argonne National Laboratory, Film Center, D-2-149, 9700 S. Cass Avenue, Argonne, Illinois, 60439.