96 An Artificial Nanoemulsion Carrying Paclitaxel Decreases the Cardiac Allograft Vasculopathy. A Study in a Rabbit Graft Model

Abstract

Purpose Cardiac Allograft Vasculopathy (CAV) is the leading cause of death after heart transplantation (HT) after the fifth year. It was previously shown that paclitaxel associated with lipidic nanoemulsions resembling LDL was able to recede atheromatous lesions in rabbits with atherosclerosis induced by high cholesterol diet. Determine whether treatment with LDE-paclitaxel reduces the incidence and degree of CAV and analyze biodistribution of LDE in rabbits undergoing HT. Methods and Materials Cervical heterotopic HT was performed in 21 rabbits fed with regular chow added with 0.5% cholesterol and cyclosporine A for 6 weeks, divided in two groups: A) 10 rabbits treated with saline intravenously (control) and B) 11 rabbits treated with LDE-paclitaxel intravenously. LDE labeled with radioactive cholesteryl ether was counted in hearts and other tissues after I.V. injection. Cross-sectional areas of coronary arteries of both native and grafts was estimated by measuring the internal elastic lamina and the lumen area. Percentage of stenosis was calculated from the difference between the area of the vessel lumen and the area of internal elastic lamina. Results Uptake of labeled LDE in transplanted hearts was fourfold higher than in native hearts (p≤0.0001). Grafts from animals treated with LDE-paclitaxel have had an improvement in the status of the coronary arteries, showed by threefold increase of the vascular lumen area (p≤0.031) and 45% reduction of stenosis (p≤0.0008). Conclusions LDE is able to concentrate in the graft, which enables the targeting of paclitaxel. Treatment with LDE-paclitaxel markedly reduced CAV, which may open a new perspective to achieve longer survival after HT.