External beam irradiation inhibits neointimal hyperplasia after injury-induced arterial smooth muscle cell proliferation.

ABSTRACT

PURPOSE: Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by smooth muscle cell proliferation. This study examines the effects of external beam irradiation on neointimal proliferation after external injury to the central artery of the rabbit ear. METHODS AND MATERIALS Thirty male New Zealand White rabbits were used in this study. Crush lesions were performed on each ear under general anesthesia and bilateral auricular nerve blockade. A single dose of 1200 cGy (n = 10), 1600 cGy (n = 10), or 2000 cGy (n = 10) gamma radiation was delivered to the left or right central artery of the ear 24 hours after injury; the contralateral central artery served as control. All rabbits were sacrificed after 21 days and the central arteries of both ears were fixed for morphometric measurements. RESULTS: Mean (+/-SD) neointimal area was 0.062 +/- 0.005 mm2 (1200 cGy), 0.022 +/- 0.005 mm2 (1600 cGy), and 0.028 +/- 0.006 mm2 in irradiated arteries compared with 0.081 +/- 0.009 mm2 in the control group. Mean (+/-SD) luminal area was 0.049 +/- 0.004 mm2 (1200 cGy), 0.059 +/- 0.002 mm2 (1600 cGy), and 0.072 +/- 0.006 mm2 (2000 cGy) in irradiated arteries compared with 0.043 +/- 0.008 mm2 in the control group. The differences in neointimal and luminal area between control and irradiated arteries were significant (p < 0.05) for the 1600 and 2000 cGy group only. CONCLUSION: We conclude that in this model, external beam X-ray irradiation was successful in reducing neointimal proliferation after injury of the central artery of the rabbit ear. Marked reductions in neointimal proliferation were demonstrated in vessels subject to 1600 and 2000 cGy radiation; a less prominent effect was noted for 1200 cGy. Whether this approach can be used successfully to inhibit restenosis in the clinical setting requires further investigation.