NDT Advance Access published online on March 22, 2006
Nephrology Dialysis Transplantation, doi:10.1093/ndt/gfl070
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1 Clinical Research Center, Samsung Biomedical Research Institute, Korea
* To whom correspondence should be addressed. Background. The main pathology of haemodialysis graft stenosis is venous neointimal hyperplasia at graft-venous anastomoses. Neointimal hyperplasia is also observed in cases of coronary artery in-stent restenosis. Paclitaxel is a chemotherapeutic agent used to treat cancer, and has been proven to inhibit neointimal hyperplasia of coronary artery in-stent restenosis. In this study, we examined whether a paclitaxel-coated haemodialysis graft could inhibit neointimal hyperplasia and prevent stenosis. Methods. We dip-coated paclitaxel on expanded polytetrafluoroethylene (ePTFE) grafts at a dose density of 0.59 µg/mm2. In vitro release tests showed an initial paclitaxel burst followed by a long-term slow release. Using ePTFE grafts with (coated group, n = 8) or without a paclitaxel coating (control group, n = 11), we constructed arteriovenous (AV) grafts connecting the common carotid artery and the external jugular vein in Landrace pigs. Results. After excluding seven pigs for technical failure, cross-sections of graft-venous anastomoses obtained 6 weeks after placing the AV grafts were analysed. Percentage luminal stenosis, ratios of intima to media in whole cross-sections, areas of intima in the peri-junctional areas (within 2 mm above and 2 mm below the graft-venous junction), and the mean thickness of intima within venous sides of cross-sections, were 60.5% (range, 41.5-60.7), 13.0 (range, 8.6-20.4), 23.7 mm2 (range, 10.8-32.1) and 2.1 mm (range, 1.1-3.0), respectively, in the control group, whereas corresponding median values in the coated group were 10.4% (range, 1.0-17.8), 1.0 (range, 0.7-5.1), 1.6 mm2 (range, 0.2-8.0) and 0.3 mm (range, 0.1-2.2). All parameters were significantly different between the two groups (P<0.05 by Mann-Whitney test). Conclusion. Paclitaxel-coated ePTFE grafts could prevent neointimal hyperplasia and the stenosis of AV haemodialysis grafts.
Orginal Article
Paclitaxel-coated expanded polytetrafluoroethylene haemodialysis grafts inhibit neointimal hyperplasia in porcine model of graft stenosis
Byung Ha Lee 1,
Hye Yeong Nam 2,
Taegun Kwon 1,
Sung Joo Kim 3,
Ghee Young Kwon 4,
Hyun Jung Jeon 1,
Hyun Jung Lim 2,
Woo kyoung Lee 2,
Jong-sang Park 2,
Jai Young Ko 5,
and
Dae Joong Kim 6 *
2 Department of Chemistry and Molecular Engineering, Seoul National University, Korea
3 Division of Vascular Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
4 Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
5 Mitech Co., Seoul, Korea
6 Division of Nephrology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Korea
Dae Joong Kim, E-mail: kimdjsmc{at}dreamwiz.com; kimdjmed@hanmail.net
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