To demonstrate the effect of γ radiation on proliferating smooth muscle cells in vivo, a standardized bilateral carotid balloon catheter arterial injury was produced in 45 rats and doses from 0-20 Gy were delivered to the right carotid artery at 24 h after injury. At 20 days after injury, cross-sectional area of intima was determined from axial histological sections. Compared to contralateral, nonirradiated balloon-injured arteries, radiation produced a significant dose-dependent reduction in intimal cross-sectional area, with a 50% decrease at 5-7.5 Gy. To determine the effect of timing of irradiation on intimal hyperplasia, 30 rats with bilateral carotid injury received unilateral cervical irradiation at doses of 1, 5 or 10 Gy administered at either 1, 3 or 5 days after injury. The radiation dose (P = 0.0002), timing of irradiation (P = 0.003) and an interaction between timing and dose (P = 0.0278) were significantly associated with reduction in neointimal cross-sectional area. To determine the effects of radiation on intimal hyperplasia at later intervals, rats irradiated with 15 (n = 5) or 20 Gy (n = 5) were euthanized at 3 months after injury. A significant persistent reduction in intimal cross-sectional area for irradiated arteries at 3 months was associated with minimal apparent radiation effects upon adjacent tissue. These data suggest that external γ irradiation at the single doses used effectively inhibits smooth muscle proliferation and intimal hyperplasia in the rat balloon catheter injury model in a time- and dose-dependent manner.

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