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Neointimal thickening after stent delivery of paclitaxel: change in composition and arrest of growth over six months

Douglas E. Drachman, MD^*, Elazer R. Edelman, MD, PhD, FACC^* , Philip Seifert, MS, Adam R. Groothuis, MS, Danielle A. Bornstein, BS, Kalpana R. Kamath, PhD, Maria Palasis, PhD, Dachuan Yang, PhD, Sepideh H. Nott, ScM and Campbell Rogers, MD, FACC^*

^* Department of Medicine, (Cardiac Catheterization Laboratory and Coronary Care Unit, Cardiovascular Division, Brigham and Women’s Hospital) Harvard Medical School, Boston, Massachusetts, USA
Harvard-M.I.T. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
Boston Scientific Corporation, Natick, Massachusetts, USA

View larger version (115K): [in a new window]   Figure 1 Photomicrographs show rabbit iliac arteries stained with Verhoeff’s tissue elastin stain after balloon denudation and stent implantation. Seven days after stenting, a thin cellular neointima separates the lumen from the internal elastic lamina in uncoated stents (A) and stents coated with poly(lactide-co--caprolactone) (B). In arteries receiving stents coated with poly(lactide-co--caprolactone) containing paclitaxel (C), no intimal thickening is seen although the media retains its cellularity. Fifty-six days after balloon denudation and stent implantation, neointimal thickening had progressed in uncoated stents (D, G) and stents coated with poly(lactide-co--caprolactone) (E, H) but remained almost undetectable in stents coated with poly(lactide-co--caprolactone) releasing paclitaxel (F, I). Original magnifications: A to F = 150x, G to I = 18x.

View larger version (18K): [in a new window]   Figure 2 Neointimal area (± standard error) after balloon denudation and stent implantation. Intimal areas 7, 28 and 56 days after implantation of uncoated (open circles), poly(lactide-co--caprolactone)-coated (closed circles) or poly(lactide-co--caprolactone)-coated paclitaxel-releasing stents (solid squares). *p = 0.004 and 0.0007 compared with uncoated and poly(lactide-co--caprolactone)-coated stents, respectively, **p = 0.003 and 0.006 compared with uncoated and poly(lactide-co--caprolactone)-coated stents, respectively.

View larger version (146K): [in a new window]   Figure 3 Photomicrographs show rabbit iliac arteries stained with Verhoeff’s tissue elastin stain six months after balloon denudation and stent implantation. (A) After uncoated stent implantation, a thick neointima separates the lumen from the internal elastic lamina. (B) After implantation of a poly(lactide-co--caprolactone)-coated paclitaxel-releasing stent, no neointima is present upon the internal elastic lamina with only a thin cap covering the stent struts. Original magnification = 290x.

View larger version (59K): [in a new window]   Figure 4 Photomicrographs of rabbit iliac arteries after stent implantation. Serial sections from four arteries stained for collagen (picrosirius red), fibrin (Mallory’s PTAH) and hyaluronan (b-PG). In arteries with uncoated stents, collagen deposition within the neointima (yellow-orange viewed under polarized light) intensifies between 28 days (A) and 180 days (D). With paclitaxel-releasing stents, although medial collagen is present, neointimal collagen is sparse after 28 (G) and 180 days (J). Neointimal fibrin (extracellular blue staining) is sparse in arteries receiving uncoated stents after 28 (B) and 180 days (E). In contrast, intense extracellular fibrin persists in vessels receiving paclitaxel-releasing stents at 28 (H) and 180 days (K). Hyaluronan (brown staining) diminishes in arteries with uncoated stents between 28 (C) and 180 days (F). In paclitaxel-releasing stents, hyaluronan persists without change between 28 (I) and 180 (L) days. *Sites of stent struts. Original magnification 120x.