Perivascular paclitaxel wraps block arteriovenous graft stenosis in a pig model.
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.
Kelly
Burnett
B
Department of Surgery, Industrial and Nuclear Engineering, University of Cincinnati, Cincinnati, OH 45267-0585, USA.
Melhem
Murad
M
Zhang
Jianhua
J
Kasting
Gerald
G
Li
Jinsong
J
Krishnamoorthy
Mahesh
M
Heffelfinger
Sue
S
Rudich
Steven
S
Desai
Pankaj
P
Roy-Chaudhury
Prabir
P
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
D000972:Antineoplastic Agents, Phytogenic; D004343:Drug Implants; D017239:Paclitaxel