title: Perivascular paclitaxel wraps block arteriovenous graft stenosis in a pig model.
abstract: 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.
  
  
  RESULTS
  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.
authors.affiliation: Department of Surgery, Industrial and Nuclear Engineering, University of Cincinnati, Cincinnati, OH 45267-0585, USA.
authors.forename: Burnett
authors.initials: B
authors.lastname: Kelly
authors.forename: Murad
authors.initials: M
authors.lastname: Melhem
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhang
authors.forename: Gerald
authors.initials: G
authors.lastname: Kasting
authors.forename: Jinsong
authors.initials: J
authors.lastname: Li
authors.forename: Mahesh
authors.initials: M
authors.lastname: Krishnamoorthy
authors.forename: Sue
authors.initials: S
authors.lastname: Heffelfinger
authors.forename: Steven
authors.initials: S
authors.lastname: Rudich
authors.forename: Pankaj
authors.initials: P
authors.lastname: Desai
authors.forename: Prabir
authors.initials: P
authors.lastname: Roy-Chaudhury
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage*; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D004195:Disease Models, Animal; D004343:Drug Implants; D006083:Graft Occlusion, Vascular / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage*; D013552:Swine; D016896:Treatment Outcome
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D004343:Drug Implants; D017239:Paclitaxel