Chronic platelet and neutrophil adhesion: a causal role for neointimal hyperplasia in in-stent restenosis.

PURPOSE To investigate the relationship between platelets and neutrophils and the progression of neointimal hyperplasia after angioplasty versus stenting of porcine coronary arteries. METHODS Balloon angioplasty or implantation of a balloon-expandable stent was randomly performed in the left and right coronary arteries of 16 Yorkshire swine; the animals were euthanized 1 hour (n=6), 24 hours (n=4), or 1 month (n=6) after the interventions. The adhesion of chromium 51-labeled platelets and indium 111-labeled neutrophils was quantified (per cm2), and histological and morphometric analyses were performed. RESULTS The acute adhesion of platelets and neutrophils observed on the injured segments 1 hour after the interventions was similar between the treated groups. However, at 24 hours, stenting was associated with 2-fold more platelets and 3-fold more neutrophils (p<0.05) than was dilation, and stented arteries remained more thrombogenic at 1 month (p<0.05). Neointimal formation was more intense after stent implantation (3.80+/-0.77 mm, p<0.05) than after dilation (0.81+/-0.21 mm), and it correlated positively with the adhesion of platelets (r=0.81, p<0.002) and neutrophils (r=0.69, p<0.01). CONCLUSIONS These results indicate that stent implantation is associated with a more intense acute and chronic, low-grade inflammatory response than is dilation. It appears that the chronic inflammatory response is, at least in part, platelet- and neutrophil-driven and contributes to the progression of neointimal proliferation after stenting.