Long-term effects of intracoronary beta-radiation in balloon and stent-injured porcine coronary arteries

Background-The data on the long-term safety and efficacy of intracoronary b eta -radiation in animal models are limited. Methods and Results-A total of 30 coronary arteries in 15 swine were subjec ted to balloon or stent injury followed by beta -radiation from a centered P-32 source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation pro cedure. The animals received aspirin for 6 months and ticlopidine for 30 da ys, Five of the 10 animals subjected to radiation died (at 5 days, 7 days, 3 months [n=2], and 4 months) as a result of layered occlusive thrombus at the intervention site (3 stent and 2 balloon injury sites). No deaths occur red in the control group. In the surviving animals, balloon-injured and irr adiated vessels showed a trend toward larger lumens than controls 2.15+/-0. 17 versus 1.80+/-0.08 min(2), P=0.06) and larger external elastic lamina ar eas (3.32+/-0.21 versus 2.62+/-0.10 mm, P=0.003). In the stent-injured vess els from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58+/-0.33. 3.16+/-0.35 and 8.12+/-0.42 mm(2) for irradiated ve ssel segments; these values were not different from those in controls (3.21 +/-0.15, 2.84+/-0.27, and 7.76+/-0.28 mm(2), respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hem orrhage were occasionally seen. Conclusion-In the long-term (6 month porcine model of restenosis, the inhib ition by intracoronary beta -radiotherapy of the neointimal formation that is known to be present at 1 month is not sustained. This lack of effect on neointimal formation after balloon and stent arterial injury is accompanied by subacute and late thrombosis that leads to cardiac death on a backgroun d of continuous aspirin but relatively brief ticlopidine treatment.