title: Paclitaxel coating on the terminal portion of hemodialysis grafts effectively suppresses neointimal hyperplasia in a porcine model.
abstract: OBJECTIVE
  The local delivery of paclitaxel onto a graft has been reported to prevent neointimal hyperplasia. Because more than half of vascular stenoses occur within 3 cm of the venous anastomosis, this study tested the effectiveness of a paclitaxel coating restricted to both ends of the expanded polytetrafluoroethylene (ePTFE) graft to reduce the amount of drug delivered.
  
  
  METHODS
  Both ends of ePTFE grafts were coated with paclitaxel at a dose of 0.58 μg/mm(2); the total amount of paclitaxel per graft was 0.66 mg. Paclitaxel-coated hemodialysis grafts 15 cm in length were surgically implanted between the common carotid artery and external jugular vein in female Landrace pigs. The animals were sacrificed 6 weeks after graft placement. Cross sections of the anastomosis sites were analyzed histomorphometrically to measure the ratio of neointimal hyperplasia to the graft area (H/G ratio) and the percentage of luminal stenosis. The experimental results were compared between grafts coated with paclitaxel at the ends only (n = 8), grafts coated over the entire length (n = 6), and uncoated control grafts (n = 6).
  
  
  RESULTS
  The mean ± standard error values of the H/G ratios for the arterial anastomosis were 0.82 ± 0.13 (control), 0.41 ± 0.09 (terminal coating), and 0.21 ± 0.04 (whole coating). The values for the venous anastomosis were 0.82 ± 0.12 (control), 0.39 ± 0.11 (terminal coating), and 0.12 ± 0.03 (whole coating). Compared with the uncoated grafts, neointimal hyperplasia was suppressed effectively in the vascular grafts coated terminally with paclitaxel (artery, P = 050; vein, P < .001). However, the suppressive effect was less than that of grafts coated with paclitaxel over the entire length. The percentages of luminal stenosis showed similar tendency to the H/G ratios.
  
  
  CONCLUSIONS
  Despite a reduced amount of the drug, paclitaxel coating applied to both ends of the ePTFE hemodialysis grafts effectively suppressed neointimal hyperplasia at the sites of anastomosis.
authors.affiliation: Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Insu
authors.initials: I
authors.lastname: Baek
authors.affiliation: Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
authors.forename: Jinsun
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jihye
authors.initials: J
authors.lastname: Park
authors.affiliation: Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Heasun
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Chemistry, College of Natural Science, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jong-Sang
authors.initials: JS
authors.lastname: Park
authors.affiliation: Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address: daejoongsmc.kim@samsung.com.
authors.forename: Dae Joong
authors.initials: DJ
authors.lastname: Kim
mesh_terms: D000818:Animals; D001807:Blood Vessel Prosthesis; D019917:Blood Vessel Prosthesis Implantation / Q000009:adverse effects / Q000295:instrumentation*; D002317:Cardiovascular Agents / Q000008:administration & dosage*; D017536:Carotid Artery, Common / Q000473:pathology / Q000601:surgery; D020099:Coated Materials, Biocompatible; D003251:Constriction, Pathologic; D004195:Disease Models, Animal; D005260:Female; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia; D007601:Jugular Veins / Q000473:pathology / Q000601:surgery; D058426:Neointima; D017239:Paclitaxel / Q000008:administration & dosage*; D011138:Polytetrafluoroethylene; D011474:Prosthesis Design; D006435:Renal Dialysis; D013552:Swine; D013997:Time Factors
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D011138:Polytetrafluoroethylene; D017239:Paclitaxel