INTRACORONARY IRRADIATION - DOSE-RESPONSE FOR THE PREVENTION OF RESTENOSIS IN SWINE

Purpose: Restenosis after percutaneous transluminal coronary angioplas ty represents, in part, a proliferative response of vascular smooth mu scle at the site of injury, We have previously shown that high-dose ra diation (20 Gy), delivered via an intracoronary Ir-192 source, causes focal medial fibrosis and markedly impairs the restenosis process afte r balloon angioplasty in swine. This study sought to delineate the dos e-response characteristics of this effect. Methods and Materials: Fort y juvenile swine underwent coronary angiography; a segment of the left coronary artery was chosen as a target for balloon injury, In 30 swin e, a 2 cm ribbon of Ir-129 was positioned at the target segment and 20 , 15, or 10 Gy were delivered to the vessel wall(10 animals/dose), Sub sequently, overdilatation balloon angioplasty was performed at the irr adiated segment, In 10 control swine, overdilatation balloon angioplas ty was performed without previous irradiation. Thirty-eight animals su rvived until sacrifice at 30 +/- 3 days, Histopathological analysis wa s performed by a pathologist in a blinded manner, The area of maximal luminal compromise within the target segment was analyzed via computer -assisted planimetry. Results: Neointimal area was decreased by 71.4% at 20 Gy and by 58.3% at 15 Gy compared with control animals (p < 0.05 for both), A stimulatory effect on smooth muscle cell proliferation w as noted at 10 Gy, with a 123% increase in neointimal area compared wi th controls (p < 0.05), Mean percent area stenosis was also reduced by 63% at 20 Gy and by 74.8% at 15 Gy compared with controls (p < 0.05 f or both). Conclusions: Intracoronary irradiation prior to overstretch balloon angioplasty markedly reduces neointima formation; this effect is dose dependent, with evidence of a significant stimulatory effect a t 10 Gy, The effective therapeutic dose range for the prevention of re stenosis in this model begins at approximately 15 Gy delivered to the vessel wall. Copyright (C) 1996 Elsevier Science Inc.