Dose-Response Effects of 32 P Radioactive Stents in an Atherosclerotic Porcine Coronary Model

Abstract

Background —Experimental studies have demonstrated that 32 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 1.0- to 12.0-μCi 32 P radioactive stents in a porcine atherosclerotic coronary model. Methods and Results —Control (n=19) and 1.0- to 12.0-μCi 32 P 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 ≥3.0 μCi 32 P (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 ≥3.0 μCi 32 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 32 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.