Intracoronary irradiation markedly reduces neointimal proliferation after balloon angioplasty in swine: Persistent benefit at 6-month follow-up

Abstract

This study examined the long-term efficacy of intracoronary irradiation for limiting neointimal proliferation after overstretch balloon angioplasty in a porcine model of restenosis. In addition, this study sought to identify any adverse late sequelae of this novel therapy for restenosis. Restenosis after coronary angioplasty represents in part a proliferative response of vascular smooth muscle at the site of injury. We have shown previously that high dose intracoronary radiation induces focal medial fibrosis and markedly reduces neointimal proliferation early after balloon angioplasty in swine. Twenty-two juvenile swine underwent intervention at a target segment of the left coronary artery. In 11 swine, a 2-cm ribbon of iridium-192 was positioned at the target segment and 2,000 cGy was delivered to the vessel wall. Subsequently, overdilation balloon angioplasty was performed at the irradiated segment. In 11 control swine, overdilation balloon angioplasty was performed without previous irradiation. Twenty animals survived and underwent histopathologic analysis at 180 +/- 8 days. Mean (+/- SD) neointimal area was 1.59 +/- 0.78 and 0.46 +/- 0.35 mm2 (p < 0.001) in control and irradiated animals, respectively. Mean percent area stenosis was 37.9 +/- 12.4% and 14.2 +/- 9.0% (p < 0.001) in the control and irradiated animals, respectively. Thus, by 6-month follow-up, intracoronary irradiation before balloon angioplasty had reduced the bulk of the neointimal lesion by 71.1% and reduced percent area stenosis by 62.5% compared with that in control animals. There was no evidence of radiation vasculopathy or myocardial damage at 6 months. Intracoronary irradiation (2,000 cGy) produces persistent impairment of neointimal proliferation 6 months after balloon injury, with no evidence of late radiation sequelae.