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

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Abstract

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 μM (31 ± 1 μg; low dose; n = 7), 0.55 ± 0.02 μM (216 ± 8 μg; high dose; n = 6), and 4.55 ± 0.1 μM (1774 ± 39 μg; 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.

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Acknowledgments

This study was funded by the Michaelideion Cardiac Center and the Medispes SW AG, Greece.

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Authors and Affiliations

  1. Michailideion Cardiac Center, Ioannina, Greece

    Dimitrios N. Lysitsas, Christos S. Katsouras, John C. Papakostas, Ioannis K. Toumpoulis, Charalampos Angelidis, Petros Bozidis, Christopher G. Thomas, Konstantin Seferiadis, Dimitris A. Sideris & Lampros K. Michalis

  2. Laboratory of Clinical Chemistry, University of Ioannina Medical School, Ioannina, Greece

    Konstantin Seferiadis & Nikolaos Psychoyios

  3. Laboratory of Biological Chemistry, University of Ioannina Medical School, Ioannina, Greece

    Stathis Frillingos

  4. Department of Oncology, University of Ioannina Medical School, Ioannina, Greece

    Nikolaos Pavlidis

  5. Department of Histology-Embryology, School of Medicine, University of Athens, Athens, Greece

    Euaggelos Marinos

  6. Department of Pathology, University Hospital of Larisa, Larisa, Greece

    Lubna Khaldi

  7. School of Medicine, University Hospital of Ioannina, University Campus, 45110, Ioannina, Greece

    Lampros K. Michalis

Authors
  1. Dimitrios N. Lysitsas
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  2. Christos S. Katsouras
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  3. John C. Papakostas
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  7. Christopher G. Thomas
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  8. Konstantin Seferiadis
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  11. Nikolaos Pavlidis
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  12. Euaggelos Marinos
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  13. Lubna Khaldi
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  14. Dimitris A. Sideris
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  15. Lampros K. Michalis
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Correspondence to Lampros K. Michalis.

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Lysitsas, D.N., Katsouras, C.S., Papakostas, J.C. et al. Antirestenotic Effects of a Novel Polymer-Coated D-24851 Eluting Stent. Experimental Data in a Rabbit Iliac Artery Model. Cardiovasc Intervent Radiol 30, 1192–1200 (2007). https://doi.org/10.1007/s00270-007-9027-4

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  • DOI: https://doi.org/10.1007/s00270-007-9027-4

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