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

Abstract

Background - Experimental studies have demonstrated that 32P 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 32P radioactive stents in a porcine atherosclerotic coronary model. Methods and Results - Control (n = 19) and 1.0- to 12.0-μCi 32P 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 (mm2) for the stents with ≥ 3.0 μCi 32P (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 32P was composed of smooth muscle cells, matrix proteoglycans, calcification, foam cells, and cholesterol clefts. Conclusions - Continuous low-dose-rate irradiation delivered by high-activity 32P 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.