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-Ci 32 P radioactive stents in a porcine atherosclerotic coronary model. Methods and Results-Control (nϭ19) and 1.0-to 12.0-Ci 32 P radioactive (nϭ43) stents (total, nϭ62) 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 (Pϭ0.54). On histology, the mean neointimal area and the percent in-stent stenosis correlated positively with increasing stent activity (rϭ0.64, PϽ0.001). The mean neointimal area (mm 2 ) for the stents with Ն3.0 Ci 32 P (3.57Ϯ1.21) was significantly greater than that for the nonradioactive stents (1.78Ϯ0.68, PϽ0.0001). The neointima of the stents with Ն3.0 Ci 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. (Circulation. 1999;100:1548-1554.)

Intracoronary β-Radiation Exacerbates Long-Term Neointima Formation in Balloon-Injured Pig Coronary Arteries

“…Carter et al 7 described increased neointima formation and adventitial fibrosis at 6 months using highactivity 32 P radioactive stents in atherosclerotic pig coronary arteries. A larger neointima and delayed neointimal healing 15 weeks after radioactive stent implantation in dog coronary arteries were also reported by Taylor et al 8 However, a sustained reduction of neointimal proliferation but incomplete vessel wall healing 1 year after the implantation of high-activity 32 P radioactive stents in rabbit iliac arteries was communicated by Farb et al 9 Compared with radioactive stents, long-term animal data on catheter-based intracoronary radiation are incomplete.…”

Three-Dimensional Intravascular Ultrasound Assessment of Noninjured Edges of β-Irradiated Coronary Segments

“…[23][24][25][26][27] Further, a recent report has shown that continuous low-dose rate irradiation delivered by radioactive stent promotes "atheromatous" neointimal formation. 28 Therefore, a question still remains to be elucidated: Does endovascular radiation have any influence on the progression of atherosclerosis, especially in the adjacent nontarget irradiated segments? Figure 3.…”

“Edge Effect” of 32 P Radioactive Stents Is Caused by the Combination of Chronic Stent Injury and Radioactive Dose Falloff

“…9 -12 There is only anecdotal evidence of the substrate of this edge effect. 13 Possible explanations for this edge phenomenon are the stimulation of tissue proliferation 14,15 or excessive extracellular matrix 16,17 by low-dose irradiation, by mechanical injury, 18 -20 or by a combination of both. The latter has been described in clinical endovascular radiotherapy as geographic miss.…”