Preliminary investigation of mitoxantrone coating on stent-grafts to inhibit neointimal proliferation.
OBJECTIVE
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.
Dirsch
Olaf
O
Institute of Pathology, University of Cologne, Germany.
Dahmen
Uta
U
Gu
Yan L
YL
Ji
Yuan
Y
Karoussos
Ira A
IA
Wieneke
Heinrich
H
Erbel
Raimund
R
D000818:Animals; D001707:Biopsy, Needle; D016893:Carotid Stenosis / Q000473:pathology / Q000628:therapy*; D002404:Catheterization / Q000295:instrumentation* / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D007150:Immunohistochemistry; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology*; D011475:Prosthesis Failure; D011817:Rabbits; D012008:Recurrence; D012016:Reference Values; D012680:Sensitivity and Specificity; D015607:Stents; D013927:Thrombosis / Q000517:prevention & control; D017539:Tunica Intima / Q000187:drug effects / Q000473:pathology*
D020099:Coated Materials, Biocompatible; D008942:Mitoxantrone