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

Background - The data on the long-term safety and efficacy of intracoronary β-radiation in animal models are limited. Methods and Results - A total of 30 coronary arteries in 15 swine were subjected to balloon or stent injury followed by β-radiation from a centered ³²P source (2000 cGy to 1 mm beyond lumen surface) or a sham radiation procedure. The animals received aspirin for 6 months and ticlopidine for 30 days. 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 occurred in the control group. In the surviving animals, balloon-injured and irradiated vessels showed a trend toward larger lumens than controls (2.15±0.17 versus 1.80±0.08 mm², P=0.06) and larger external elastic lamina areas (3.32±0.21 versus 2.62±0.10 mm², P=0.003). In the stent-injured vessels from surviving animals, lumen, neointimal, and external elastic lamina areas were 3.58±0.33, 3.16±0.35, and 8.12±0.42 mm² for irradiated vessel segments; these values were not different from those in controls (3.21±0.15, 2.84±0.27, and 7.76±0.28 mm², respectively). Histologically, healing was complete in most survivors, although intramural fibrin and hemorrhage were occasionally seen. Conclusion - In the long-term (6 month) porcine model of restenosis, the inhibition by intracoronary β-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 background of continuous aspirin but relatively brief ticlopidine treatment.