title: Reduction in neointimal formation with a stent coated with multiple layers of releasable heparin in porcine coronary arteries.
abstract: 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.
authors.affiliation: Department of Cardiovascular Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Matsumoto
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.forename: Kunio
authors.initials: K
authors.lastname: Morishige
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Eto
authors.forename: Akira
authors.initials: A
authors.lastname: Takeshita
mesh_terms: D015906:Angioplasty, Balloon, Coronary; D000818:Animals; D020099:Coated Materials, Biocompatible; D017023:Coronary Angiography; D023903:Coronary Restenosis / Q000473:pathology*; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000473:pathology*; D006493:Heparin / Q000494:pharmacology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D015607:Stents; D013552:Swine; D017539:Tunica Intima / Q000473:pathology*; D018084:Ultrasonography, Interventional
chemical_list: D020099:Coated Materials, Biocompatible; D018809:Proliferating Cell Nuclear Antigen; D006493:Heparin