EFFECTS OF ENDOVASCULAR RADIATION FROM A BETA-PARTICLE-EMITTING STENTIN A PORCINE CORONARY RESTENOSIS MODEL - A DOSE-RESPONSE STUDY

Background Neointimal formation causes restenosis after intracoronary stent placement. Endovascular radiation delivered via a stent has been shown to reduce neointimal formation after placement in porcine and r abbit iliac arteries. The objective of this study was to evaluate the dose-related effects of a beta-particle-emitting radioactive stent in a porcine coronary restenosis model. Methods and Results Thirty-seven swine underwent placement of 35 nonradioactive and 39 beta-particle-em itting stents with activity levels of 23.0, 14.0, 6.0, 3.0, 1.0, 0.5, and 0.15 mu Ci of P-32. Treatment effect was assessed by histological analysis 28 days after stent placement. Neointimal and medial smooth m uscle cell density were inversely related to increasing stent activity . The neointima of the high-activity (3.0- to 23.0-mu Ci) scents consi sted of fibrin, erythrocytes, occasional inflammatory cells, and smoot h muscle cells with partial endothelialization of the luminal surface. In the 1.0-mu Ci stents, the neointima was expanded and consisted of smooth muscle cells and a proteoglycan-rich matrix. The neointima of t he low-activity (0.15- and 0.5-mu Ci) stents was composed of smooth mu scle cells and matrix with complete endothelialization of the luminal surface. At low and high stent activities, there was a reduction in ne ointimal area (low, 1.63+/-0.67 mm(2) and high, 1.73+/-0.97 mm(2) vers us control, 2.40+/-0.87 mm(2)) and percent area stenosis (low, 26+/-7% and high, 26+/-12%) compared with control stents (37+/-12%, P less th an or equal to.01). The 1.0-mu Ci stents, however, had greater neointi mal formation (4.67+/-1.50 mm(2)) and more luminal narrowing (64+/-16% ) than the control stents (P<.0001). Conclusions The differential resp onse to the doses of continuous beta-particle irradiation used in this experimental model suggests a complex biological interaction of endov ascular radiation and vascular repair after stent placement. Further s tudy is required to determine the clinical potential for this therapy to prevent stent restenosis.