Dose-response effects of 32P radioactive stents in an atherosclerotic porcine coronary model

Background-Experimental studies have demonstrated that P-32 radioactive tents reduce neointimal formation at 28 days in porcine iliac and coronary arteries. Our objective was to determine the long-term dose-response effects of 1.0- to 12.0-mu Ci P-32 radioactive stents in a porcine atherosclerotic coronary model. Methods ana Results-Control (n=19) and 1.0- to 12.0-mu Ci P-32 radioactive (n=43) stents (total, n=62) were implanted in the coronary arteries of 31 miniature swine at 28 days after creation of a fibrocellular plaque by overstretch balloon injury and cholesterol feeding. Angiography and histomorphometry were performed at 6 months. Stent thrombosis occurred in 3 radioactive (7.7%) and no control stents (P=0.54). On histology, the mean neointimal area and the percent in-stent stenosis correlated positively with increasing stent activity (r= 0.64, P<0.001). The mean neointimal area (mm(2)) for the stents with greater than or equal to 3.0 mu Ci P-32 (3.57+/-1.21) was significantly greater than that for the nonradioactive stents (1.78 +/- 0.68, P<0.0001). The neointima of the stents with greater than or equal to 3.0 mu Ci P-32 was composed of smooth muscle cells, matrix proteoglycans, calcification, foam cells, and cholesterol clefts. Conclusions-Continuous low-dose-rate irradiation delivered by high-activity P-32 radioactive stents promotes the formation of an '"atheromatous" neointima after 6 months in this experimental model. These data may be useful for predicting late tissue responses to radioactive stents in human coronary arteries.