The Inhibition of Neointimal Hyperplasia by Combination of External Radiation and Paclitaxel in A Rat Carotid Injury Model

ABSTRACT

BACKGROUND AND OBJECTIVES: Radiation therapy is one of the promising new treatment for restenosis, which is a major problem for the long-term success after angioplasty. We compared radiation therapy only and combined therapy of paclitaxel and radiation on neointimal hyperplasia after injury of rat carotid artery to see whether we can reduce the effective dosage of radiation and thus diminish untoward consequence of radiation if paclitaxel could function as a cell-cycle selective radiosensitizer. MATERIAL AND METHODS: A standardized carotid balloon catheter arterial injury was produced in 65 rats. First group was composed of a single dose of paclitaxel 1 mg/kg body weight, 2 mg/kg or 4 mg/kg, which was administrated intraperitoneally at 2 hours after injury. Second group received external radiation at doses of 2.5 or 5 Gy at 24 hours after injury. Third group was treated with combined paclitaxel-radiation: paclitaxel was injected at 2 hours after injury and then external radiation was delivered 24 hours later. At 21 days after injury, the cross-sectional area of neointima and the ratio of intima/medial area were determined from axial sections using image analysis. RESULTS: Single dose of paclitaxel had no effect in reducing smooth muscle cell proliferation. Minimum effective single dose to inhibit neointimal hyperplasia was 5 Gy. Combined paclitaxel-radiation group except subgroup with paclitaxel 1 mg/kg and 2.5 Gy radiation showed significant reduction of neointimal area compared to group with 2.5 Gy radiation. CONCLUSION: Low-dose external radiation combined with paclitaxel can more effectively inhibit smooth muscle cell pro-liferation and neointimal hyperplasia than radiation only in the rat carotid injury model.