Fibrocellular tissue responses to endovascular and external beam irradiation in the porcine model of restenosis

Purpose: Endovascular radiation has reduced postangioplasty restenosis in preclinical and early clinical studies. External radiation treatment may have advantages over endovascular therapy. We examined vascular and perivascular tissue responses to endovascular and external irradiation in pig coronary arteries. Methods and Materials: Ninety-one animals received endovascular or external radiation following balloon injury and were sacrificed at 14, 30, or 180 days. Injured segments of coronary vessels including perivascular and myocardial tissues were evaluated with histochemistry. Results: Endovascular radiation was associated with delayed arterial wound healing as late as 6 months, evidenced by paucity of smooth muscle α-actin in neointimal cells compared to control. External treatment was associated with increased collagen in neointima and adventitia, and focal interstitial necrosis in adjacent myocardium. Conclusions: These investigations showed whole-heart 14 Gy external radiation treatment following coronary injury exacerbated certain aspects of arterial healing. In addition focal myocardial necrosis and fibrosis was observed following external but not endovascular irradiation. Endovascular radiation has some advantages over external irradiation; however the persistence of a synthetic smooth muscle cell phenotype in the neointima at 6 months suggests ionizing radiation in general may have profound effects on vessel architecture over the long term.