Preliminary investigation of mitoxantrone coating on stent-grafts to inhibit neointimal proliferation.

Abstract

PURPOSE: To investigate the inhibition of neointimal proliferation induced by a stent-graft loaded with mitoxantrone. METHODS: Stent-grafts with and without mitoxantrone loading (150 microg per device) were inserted into the carotid artery of 7 and 6 rabbits, respectively. After an observation period of 28 days, the animals were sacrificed, and a detailed morphological and morphometric workup of the stented vessels was performed. RESULTS: Uncoated stent-grafts induced a thick neointima (median diameter 97+/-99 microm), whereas no neointima formed in mitoxantrone-loaded stent-grafts. However, the loaded devices were not fully covered by an endothelial layer. The underlying media was significantly thinner (31.8+/-5.6 versus 48.6+/-3.3 microm, p=0.002) and showed a widespread loss of smooth muscle cells. CONCLUSIONS: Mitoxantrone loading of a stent-graft inhibited the formation of a neointima. However, important regenerative processes were prevented as well, indicating a local overdose. More experiments using lower doses are warranted.