Paclitaxel-coated expanded polytetrafluoroethylene haemodialysis grafts inhibit neointimal hyperplasia in porcine model of graft stenosis.
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 microg/mm(2). 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 mm(2) (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 mm(2) (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).


CONCLUSIONS
Paclitaxel-coated ePTFE grafts could prevent neointimal hyperplasia and the stenosis of AV haemodialysis grafts.
Clinical Research Center, Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
Byung Ha
BH
Lee
Hye Yeong
HY
Nam
Taegun
T
Kwon
Sung Joo
SJ
Kim
Ghee Young
GY
Kwon
Hyun Jung
HJ
Jeon
Hyun Jung
HJ
Lim
Woo Kyoung
WK
Lee
Jong-sang
JS
Park
Jai Young
JY
Ko
Dae Joong
DJ
Kim
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D001166:Arteriovenous Shunt, Surgical / Q000295:instrumentation*; D001807:Blood Vessel Prosthesis; D020099:Coated Materials, Biocompatible; D004195:Disease Models, Animal; D005465:Fluorocarbon Polymers; D006083:Graft Occlusion, Vascular / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006965:Hyperplasia / Q000473:pathology / Q000517:prevention & control; D066298:In Vitro Techniques; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology*; D011474:Prosthesis Design; D006435:Renal Dialysis / Q000009:adverse effects*; D013552:Swine; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D000972:Antineoplastic Agents, Phytogenic; D020099:Coated Materials, Biocompatible; D005465:Fluorocarbon Polymers; C010946:polytetrafluoroethane; D017239:Paclitaxel