Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model

Journal Article · Thu Nov 15 00:00:00 EST 2007 · Cardiovascular and Interventional Radiology

DOI:https://doi.org/10.1007/S00270-007-9027-4· OSTI ID:21090765

Lysitsas, Dimitrios N; Katsouras, Christos S; Papakostas, John C; Toumpoulis, Ioannis K; Angelidis, Charalampos; Bozidis, Petros; Thomas, Christopher G; Seferiadis, Konstantin ^[1]; Psychoyios, Nikolaos ^[2]; Frillingos, Stathis ^[3]; Pavlidis, Nikolaos ^[4]; Marinos, Euaggelos ^[5]; Khaldi, Lubna ^[6]; Sideris, Dimitris A

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1. Michailideion Cardiac Center (Greece)
2. University of Ioannina Medical School, Laboratory of Clinical Chemistry (Greece)
3. University of Ioannina Medical School, Laboratory of Biological Chemistry (Greece)
4. University of Ioannina Medical School, Department of Oncology (Greece)
5. University of Athens, Department of Histology-Embryology, School of Medicine (Greece)
6. University Hospital of Larisa, Department of Pathology (Greece)

Experimental and clinical data suggest that stents eluting antiproliferative agents can be used for the prevention of in-stent restenosis. Here we investigate in vitro the antiproliferative and apoptotic effect of D-24851 and evaluate the safety and efficacy of D-24851-eluting polymer-coated stents in a rabbit restenosis model (n = 53). Uncoated stents (n = 6), poly (dl-lactide-co-glycolide) (PLGA)-coated stents (n = 7), and PLGA-coated stents loaded with 0.08 {+-} 0.0025 {mu}M (31 {+-} 1 {mu}g; low dose; n = 7), 0.55 {+-} 0.02 {mu}M (216 {+-} 8 {mu}g; high dose; n = 6), and 4.55 {+-} 0.1 {mu}M (1774 {+-} 39 {mu}g; extreme dose; n = 5) of D-24851 were randomly implanted in New Zealand rabbit right iliac arteries and the animals were sacrificed after 28 days for histomorphometric analysis. For the assessment of endothelial regrowth in 90 days, 12 rabbits were subjected to PLGA-coated (n = 3), low-dose (n = 3), high-dose (n = 3), and extreme-dose (n = 3) stent implantation. In vitro studies revealed that D-24851 exerts its growth inhibitory effects via inhibition of proliferation and induction of apoptosis without increasing the expression of heat shock protein-70, a cytoprotective and antiapoptotic protein. Treatment with low-dose D-24851 stents was associated with a significant reduction in neointimal area and percentage stenosis only compared with bare metal stents (38% [P = 0.029] and 35% [P = 0.003] reduction, respectively). Suboptimal healing, however, was observed in all groups of D-24851-loaded stents in 90 days in comparison with PLGA-coated stents. We conclude that low-dose D-24851-eluting polymer-coated stents significantly inhibit neointimal hyperplasia at 28 days through inhibition of proliferation and enhancement of apoptosis. In view of the suboptimal re-endothelialization, longer-term studies are needed in order to establish whether the inhibition of intimal growth is maintained.

• OSTI ID: 21090765
• Journal Information: Cardiovascular and Interventional Radiology, Vol. 30, Issue 6; Other Information: DOI: 10.1007/s00270-007-9027-4; Copyright (c) 2007 Springer Science+Business Media, LLC; Country of input: International Atomic Energy Agency (IAEA); ISSN 0174-1551
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
APOPTOSIS
ARTERIES
HEALING
HEAT-SHOCK PROTEINS
IN VITRO
INHIBITION
POLYMERS
RABBITS