High concentration of paclitaxel coated graft for hemodialysis elicits a severe foreign body response in a porcine model

Abstract

The most crucial reason for vascular access dysfunction in hemodialysis patients is stenosis caused by neointimal hyperplasia. Until now, paclitaxel has been shown to act as a great anti-proliferative agent and effectively lowers stenosis on graft-venous anastomosis sites. Dipping method allows us to obtain paclitaxel coated Arteriovenous (AV) expanded polytetrafluoroethylene (ePTFE) grafts in a quick, uniform and facile manner. As the whole graft surface elutes paclitaxel upon implantation by systemic circulation, I ought to validate how various amounts of paclitaxel release affect a porcine system. I coated the following concentrations of paclitaxel for study- Control (0 ug/mm2), Group 1 (0.14ug/mm2), Group 2 (0.28ug/mm2), Group 3 (0.51ug/mm2), Group4 (1.11ug/mm2), and Group 5 (2.22ug/mm2). This work uncovers that in general, paclitaxel coated grafts revealed high level of patency compared to the control group in which grafts were almost all occluded, however

at high concentrations of paclitaxel, the surrounding tissue and the graft retained little affinity. I attribute this for a foreign body response and hence arise necessity to tune the amount of paclitaxel in order to minimize both stenosis and foreign body response.