ENDOVASCULAR LOW-DOSE IRRADIATION INHIBITS NEOINTIMA FORMATION AFTER CORONARY-ARTERY BALLOON INJURY IN SWINE - A POSSIBLE ROLE FOR RADIATION-THERAPY IN RESTENOSIS PREVENTION

Background Restenosis after percutaneous transluminal coronary angiopl asty remains a major limitation of the longterm success of this proced ure. Restenosis is a form of wound healing. Low-dose ionizing radiatio n has been effective in inhibiting exuberant wound healing responses i n a variety of clinical situations. Methods and Results Vascular neoin timal lesions resembling human restenosis were created in the coronary arteries of normal pigs by overstretch balloon angioplasty injury. To test the effect of low-dose endovascular gamma radiation on lesion fo rmation, a high-activity Ir-192 source was introduced into one of the injured arteries in each animal and left in place for a period suffici ent to deliver one of three doses: 350, 700, or 1400 cGy. To test pote ntial benefits of delayed irradiation, 700 cGy was given in another gr oup 2 days after injury. Animals were killed 14 days after balloon inj ury and the coronary vasculature was pressure-perfusion fixed. To test the late effect and safety of endovascular low-dose irradiation, 700 or 1400 cGy was given in miniswine coronary arteries after injury as w ell as in noninjured carotid arteries; this group was followed up for 6 months. Tissue sections were measured by computer-assisted planimetr y. All arteries treated with radiation demonstrated significantly decr eased neointima formation compared with control arteries. The ratio of intimal area-to-medial fracture length (IA/FL) was inversely correlat ed with the different radiation doses: control, 0.59; 350 cCy, 0.38; 7 00 cGy, 0.42; and 1400 cGy, 0.17 (r = -0.75, P<.0001). Delay of 700-cG y irradiation for 2 days after injury significantly decreased neointim a formation compared with the same dose given immediately after injury . Analysis of long-term specimens showed reduction of IA/FL in the art eries irradiated with 700 cGy (0.3, P=.009) and 1400 cGy (0.31, P=.001 ) compared with control arteries (0.50). There was no excess fibrosis in the media, adventitia, or perivascular space of the coronary arteri es or adjacent myocardium in pigs that received radiation compared wit h control animals. Conclusions Low-dose intracoronary irradiation deli vered to the site of coronary arterial overstretch balloon injury in p igs inhibited subsequent intimal thickening (hyperplasia). A dose-resp onse relationship was demonstrated, and delay of treatment for 48 hour s appeared to augment the inhibitory effect. Six months of follow-up w ithout fibrosis or arteriosclerosis demonstrated the durability of the beneficial effect in the treated group. These data suggest that intra coronary irradiation therapy may aid in preventing clinical restenosis .