Gamma irradiation inhibits neointimal hyperplasia in rats after arterial injury.

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Abstract
Restenosis complicates a significant proportion of endovascular and open vascular procedures such as carotid endarterectomy. In contrast to the primary atheroma, restenosis is characterized by intimal hyperplasia of vascular smooth muscle cells. We hypothesized that gamma radiation would reduce restenosis by limiting intimal hyperplasia after arterial injury. To demonstrate the effect of gamma radiation on smooth muscle hyperplasia in vivo, a standardized bilateral carotid balloon catheter arterial injury was produced in 37 rats. A single dose of 750, 1500, or 2250 cGy (1cGy = 1 rad) gamma radiation was delivered to the right carotid artery at either 1 or 2 days after injury; the shielded contralateral carotid artery served as matched control. At 21 days after injury, vessels were perfusion-fixed in situ, and cross-sectional area of neointima was determined from axial sections using image analysis. Marked reductions in neointimal cross-sectional area were demonstrated in vessels subjected to 1500- and 2250-cGy radiation at both 1 and 2 days after injury. A less prominent effect was noted for 750 cGy, reaching statistical significance only at 2 days after injury. By two-way ANOVA, radiation dose (P = .0002), timing of radiation delivery (P = .003), and an interaction between timing and dose (P = .0278) were significantly associated with reduction in neointimal cross-sectional area. At 1500 cGy, delivery of radiation 1 day after injury inhibited neointimal hyperplasia more prominently than the same dose 2 days after injury; a dose-response relation was evident at 1 day. Radiation may be an important adjunctive therapy for reducing the incidence of restenosis after angioplasty or endarterectomy.