Dose-Response Effects of P Radioactive Stents in an Atherosclerotic Porcine Coronary Model

Background—Experimental studies have demonstrated that P radioactive stents reduce neointimal formation at 28 days in porcine iliac and coronary arteries. Our objective was to determine the long-term dose-response effects of 1.0to 12.0-mCi P radioactive stents in a porcine atherosclerotic coronary model. Methods and Results—Control (n519) and 1.0to 12.0-mCi P radioactive (n543) stents (total, n562) 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 (P50.54). On histology, the mean neointimal area and the percent in-stent stenosis correlated positively with increasing stent activity (r50.64, P,0.001). The mean neointimal area (mm) for the stents with $3.0 mCi P (3.5761.21) was significantly greater than that for the nonradioactive stents (1.7860.68, P,0.0001). The neointima of the stents with $3.0 mCi P 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 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. (Circulation. 1999;100:1548-1554.)