Dose-dependent radiation effect on microvasculature and repair

Abstract

It has been postulated that the damage to microvasculature may be a major factor in the manifestation of late radiation damage to organized tissue. In this study, the radiation damage to microvasculature was investigated in a rabbit model during the early phases of irradiation with the use of vascular permeability as a marker. By means of a triple isotopic technique, the vascular, extravascular, and intracellular spaces could be defined. A forelimb and hindlimb of New Zealand White rabbits were irradiated with single doses of 2-30 Gy. 125I- and 131I-labeled bioscreened albumin were used to determine the changes in vascular permeability due to irradiation. The rabbits were sacrificed at various intervals post irradiation. Vascular and extravascular spaces and the respective albumin concentrations in tissue samples from irradiated limbs were compared with control values from the unirradiated contralateral limbs in each animal. The results indicated a definite increase in the vascular permeability of albumin secondary to irradiation. The increase in vascular permeability was apparent instantaneously with irradiation, even at 2 Gy. The microvascular compromise appear to be dose related. When examined at 16-24 hours post irradiation, the excess extravasation of albumin was significant at and beyond 8 Gy. At 10-30 days post irradiation, injury was not apparent up to 15 Gy. Thus there appeared to be an instantaneous injury at the capillary level due to irradiation, which appeared to be dose related. A repair process became evident as early as 16-24 hours and appeared to be dose related as well as related to elapsed time post irradiation.