External Radiation for Restenosis

Background: Restenosis after balloon angioplasty remains a substantial clinical problem. Endovascular radiation has been shown to reduce neointima formation in animal models of restenosis, and the results of early clinical trials are promising. However, this technique has several limitations, particularly, the inability to delay or fractionate therapy and inhomogeneous dose distribution. These shortcomings might be overcome by delivering radiation therapy from an external approach. This study investigated the effects of high dose external beam irradiation on balloon‐injured pig coronary arteries. Methods and Results: Eight domestic juvenile pigs underwent balloon overstretch injury. External beam irradiation (21 Gy) of the heart was performed within 2 hours on four pigs and the remainder were not irradiated (controls). Sections of paraffin embedded injured arteries, perfusion fixed at 4 weeks, were measured by computer‐assisted histomorphometry. Luminal area in the 21‐Gy group was 3.84 ± 1.80 mm2 compared to 2.0 4 ± 0.49 mm2 in the controls (P < 0.01). Neointimal area and maximal intimal thickness were reduced in the 21‐Gy group (0.23 ± 0.36 vs 1.36 ± 0.67mm2, P < 0.0005; 0.25 ± 0.35 vs 0.64 ± 0.2, P < 0.01, respectively). Diffuse focal interstitial fibrosis was observed in the myocardium of the irradiated group. Conclusions: At 21 Gy, external beam irradiation significantly increased lumen size and reduced neointima formation in balloon‐injured pig coronary arteries. However, myocardial damage was also induced by irradiation of the whole heart at this dose.