Granulomatous 'foreign body reactions' contribute to exaggerated in-stent restenosis

Background: Results of previous studies with stents coated with 'biocompatible' polymers showed that severe inflammatory reaction and subsequent in-stent restenosis may occur. Objective To evaluate the contribution of granulomatous reaction from uncoated stents to formation of in-stent neointimal hyperplasia. Methods Uncoated stainless-steel stents were implanted into 21 porcine coronary arteries without oversizing and harvested after 2 months (n=6) or 6 months (n=7). We compared the stents with granulomatous reaction with those without foreign-body reaction. Results Granulomatous reactions occurred in five of 21 stents and resulted in there being significantly greater in-stent neointimal hyperplasia than there was with stents without foreign-body reaction (angiographic diameter stenosis 45 ± 36 versus 16 ± 16%, area of neointimal 3.30 ± 1.4 versus 1.22 ± 0.4 mm², thickness of neointima 0.46 ± 0.29 versus 0.11 ± 0.09 mm, stenosed area 56 ± 24 versus 20 ± 7%, P<0.01 for each comparison). This increase in amount of neointima was accompanied by significantly greater proliferating cell nuclear antibody staining (15 ± 5 versus 3 ± 2%, P<0.05) in the presence of a granuloma near the stent struts. Conclusions A localized granulomatous reaction is associated with a significant increase in amount of stent neointima and proliferation of cells. Thus, permanent stent implants may provoke granulomatous vascular reactions that may affect late-healing responses and clinical outcomes. Coronary Artery Dis 10:9-14