NDT Advance Access originally published online on July 5, 2006
Nephrology Dialysis Transplantation 2006 21(9):2425-2431; doi:10.1093/ndt/gfl250
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Experimental Nephrology
Perivascular paclitaxel wraps block arteriovenous graft stenosis in a pig model
1 Department of Surgery, 2 Department of Medicine, 3 Department of Pathology, 4 College of Pharmacy and 5 Department of Mechanical Industrial and Nuclear Engineering, University of Cincinnati, Cincinnati, OH, USA
Correspondence and offprint requests to: Prabir Roy-Chaudhury MD, PhD, Division of Nephrology, University of Cincinnati, MSB G-251, 231, Albert Sabin Way, Cincinnati, OH 45267-0585, USA. Email: Prabir.Roychaudhury{at}uc.edu
Background. Haemodialysis vascular access dysfunction is currently a huge clinical problem. In an attempt to reduce the morbidity associated with haemodialysis vascular access dysfunction, we have previously developed and validated a local perivascular paclitaxel release system that has been shown to release paclitaxel for at least 3 weeks. The aim of the current study was to evaluate the in vivo use of these perivascular wraps (for both safety and efficacy) at different time points in our pig model of arteriovenous graft stenosis.
Methods. Paclitaxel-loaded ethylene vinyl acetate wraps were placed around the graft-vein anastomosis on one side, with control polymers being placed on the contralateral side in our pig model of arteriovenous graft stenosis. Animals were sacrificed at early (10–11 days), middle (23–24 days) and late (32–38 days) time points. The entire graft-vein anastomosis was removed at the time of sacrifice and assessed for the extent of luminal stenosis using histomorphometric techniques.
Result. Graft-vein anastomoses treated with the paclitaxel-loaded polymers had an almost complete absence of luminal stenosis at the middle (23–24 days) and late (32–38 days) time points (when one would expect the development of neointimal hyperplasia) as compared with the contralateral control graft-vein anastomoses (37.90% luminal stenosis in the controls vs 0.10% in the paclitaxel group). There were minimal local side effects from this procedure.
Conclusions. Our results demonstrate the safety and efficacy of paclitaxel-loaded perivascular wraps in the setting of a pig model of arteriovenous graft stenosis. We believe that such a local approach which could be easily applied at the time of surgery is ideally suited for use in the clinical setting of haemodialysis vascular access dysfunction. It is likely that this novel approach could result in a significant reduction in the huge economic and health morbidity costs currently associated with this recalcitrant clinical problem.
Keywords: anti-proliferative therapy; dialysis access stenosis; haemodialysis vascular access dysfunction; local drug delivery; neointimal hyperplasia; perivascular drug delivery
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