title: Suppression of neointimal hyperplasia by sirolimus-eluting expanded polytetrafluoroethylene (ePTFE) haemodialysis grafts in comparison with paclitaxel-coated grafts.
abstract: BACKGROUND
  Haemodialysis vascular access dysfunction caused by aggressive venous neointimal hyperplasia is a major problem for haemodialysis patients with synthetic arteriovenous (AV) grafts. Several different strategies to prevent venous stenosis by inhibiting smooth muscle cell proliferation and migration using local delivery of potent antiproliferative agents are currently under investigation. We performed this study to evaluate the efficacy of sirolimus-eluting vascular grafts in preventing stenosis and to compare the effectiveness of sirolimus-coated grafts with that of paclitaxel-coated vascular grafts that we characterized in a previous study.
  
  
  METHODS
  AV grafts were implanted laterally between the common carotid artery and external jugular vein of 14 female Landrace pigs. Three types of grafts were implanted: grafts coated with 1.08 μg/mm(2) sirolimus (low dose, n = 6), grafts coated with 2.41 μg/mm(2) sirolimus (high dose, n = 2) and uncoated control grafts (n = 6). Animals were sacrificed 6 weeks after surgery. Cross-sections of the venous anastomoses were analysed to determine the percentage of luminal stenosis in each group, and immunohistochemistry was performed to identify the cellular phenotypes of the neointimal hyperplasia and tissues adjacent to the implanted grafts.
  
  
  RESULTS
  Compared with the control group, neointimal hyperplasia in the venous anastomoses of the groups implanted with sirolimus-coated vascular grafts was significantly suppressed without infection. The mean ± standard error values for the percentage of luminal stenosis were 75.7 ± 12.7% in the control group and 22.2 ± 1.41% in the low-dose sirolimus-coated group. Myofibroblasts and fibroblasts were the major cell types found in the neointimal hyperplasia.
  
  
  CONCLUSIONS
  Neointimal hyperplasia was effectively suppressed by sirolimus-eluting grafts. However, the inhibitory effects of sirolimus-eluting grafts were weaker than those observed for paclitaxel-coated grafts in our previous study.
authors: Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Republic of Korea.
authors: Insu
authors: I
authors: Baek
authors: Cheng Zhe
authors: CZ
authors: Bai
authors: Jinsun
authors: J
authors: Hwang
authors: JiHye
authors: J
authors: Park
authors: Jong-Sang
authors: JS
authors: Park
authors: Dae Joong
authors: DJ
authors: Kim
mesh_terms: D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000379:methods; D002339:Carotid Arteries / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D003251:Constriction, Pathologic / Q000473:pathology / Q000517:prevention & control; D005260:Female; D006083:Graft Occlusion, Vascular / Q000473:pathology / Q000517:prevention & control; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D007601:Jugular Veins / Q000601:surgery; D023421:Models, Animal; D058426:Neointima / Q000473:pathology* / Q000517:prevention & control*; D017239:Paclitaxel / Q000627:therapeutic use*; D011138:Polytetrafluoroethylene / Q000627:therapeutic use*; D006435:Renal Dialysis / Q000379:methods*; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*; D013552:Swine; D058017:Vascular Grafting / Q000379:methods*
chemical_list: D011138:Polytetrafluoroethylene; D017239:Paclitaxel; D020123:Sirolimus