Recent studies demonstrated that neointimal formation, which is caused by both neointimal proliferation and organized mural
thrombus, is responsible for in-
stent restenosis. Although various types of
heparin coatings were effective in reducing (sub)acute
thrombosis, most of them failed to reduce neointimal proliferation. This study was designed to examine the effect of the
stent coated with multiple layers of releasable
heparin complex from which
heparin diffuses into the surrounding tissue and exerts its beneficial effects. Male Yorkshire pigs underwent balloon expandable stenting for coronary segments of both the left anterior and the left circumflex coronary arteries with a comparable diameter (n = 10). The
stent implantation site was randomized for either control or
heparin-coated
stent. Four weeks after the procedure, quantitative coronary angiography (QCA) and intravascular ultrasonographic imaging (IVUS) were performed followed by histologic analysis. In additional animals, staining for
proliferating cell nuclear antigen (
PCNA) was performed 10 d after the procedure (n = 3). QCA demonstrated that coronary diameter (mm) was significantly larger at the
heparin-coated
stent site (2.32 +/- 0.14) compared with the control
stent site (1.81 +/- 0.17) (p < 0.01). IVUS also showed that the neointimal area (mm2) was significantly suppressed at the
heparin-coated
stent site (2.12 +/- 0.58) compared with the control
stent site (3.92 +/- 0.33) (p < 0.01). Histologic analysis also demonstrated that neointimal area (mm2) was significantly less at the
heparin-coated
stent (2.94 +/- 0.43) than at the control
stent site (4.41 +/- 0.38) (p < 0.01), which was also the case for organized
thrombus area (x10-4 mm2) (6.61 +/- 2.67 vs. 19.36 +/- 4.38, p < 0.01). The frequency of
PCNA-positive vascular smooth muscle cells (%) was significantly less at the
heparin-coated
stent (10.8 +/- 1.0) than at the control
stent site (19.1 +/- 1.7) (p < 0.01). These results suggest that the
stent coated with releasable
heparin is beneficial in reducing neointimal formation and subsequent in-
stent restenosis.