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

To investigate the relationship between platelets and neutrophils and the progression of neointimal hyperplasia after angioplasty versus stenting of porcine coronary arteries.

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.

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).

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.