CardioVascular and Interventional Radiology

, Volume 28, Issue 1, pp 60–65 | Cite as

Stent-Based Nitric Oxide Delivery Reducing Neointimal Proliferation in a Porcine Carotid Overstretch Injury Model

  • Dongming HouEmail author
  • Hugh Narciso
  • Kirti Kamdar
  • Ping Zhang
  • Bruce Barclay
  • Keith L. March



The effects of nitric acid (NO) on vessel response to injury include the inhibition of platelet adhesion, platelet aggregation, leukocyte adhesion and smooth muscle cell proliferation. Releasing NO from a stent might reduce the clinical problem of restenosis. The present study was designed to examine whether an NO-eluting covered stent can prevent neointimal formation in a porcine carotid overstretch injury model.


The interior of a self-expanding polytetrafluoroethylene (ePTFE)-covered aSpire stent was coated with silicone, which contained 23.6 μg or 54.5 μg sodium nitroprusside (SNP, NO-releasing compound). The stent was implanted into carotid artery. Six pigs were implanted with stents, one high-dose SNP and one uncoated control, following balloon overstretch injury of the carotid artery with a balloon-to-artery ratio of 1.3:1.


No local or systemic toxicity was evidenced in the six pigs after carotid artery implantation with either low- or high-dose stents within a week. At day 28, the mean intimal thickness was 0.12 ± 0.05 mm for NO-eluting stents and 0.43 ± 0.09 mm for uncoated stents (p = 0.008). The mean neointimal area was reduced from 2.40 ± 0.39 mm2 for control stents to 0.49 ± 0.16 mm2 for NO-eluting stents (p < 0.0001), which resulted in a 24% reduction of angiographic vessel narrowing.


The NO-eluting ePTFE-covered stent is feasible and effectively reduces in-stent neointimal hyperplasia at 28 days in a porcine carotid overstretch model.


NO Stent Carotid Balloon injury 



This work was supported by Vascular Architects, Inc. D.M.H. and K.L.M. express their gratitude to the Cryptic Masons Medical Research Foundation for their support of the ICVBM, and Larry Solomon for his excellent technical assistance.


  1. 1.
    Liermann, DD, Bauernsachs, R, Schopohl, B,  et al. 1997Five year follow-up after brachytherapy for restenosis in peripheral arteriesSemin Interv Cardiol2133137PubMedGoogle Scholar
  2. 2.
    Poon, M, Badimon, JJ, Fuster, V 2002Overcoming restenosis with sirolimus: From alphabet soup to clinical realityLancet359619622PubMedGoogle Scholar
  3. 3.
    Suzuki, T, Kopia, G, Hayashi, S,  et al. 2001Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary modelCirculation10411881193Google Scholar
  4. 4.
    Sousa, JE, Costa, MA, Abizaid, AC,  et al. 2001Sustained suppression of neointimal proliferation by sirolimus-eluting stents: One-year angiographic and intravascular ultrasound follow-upCirculation10420072011Google Scholar
  5. 5.
    Degertekin, M, Serruys, PW, Foley, DP,  et al. 2002Persistent inhibition of neointimal hyperplasia after sirolimus-eluting stent implantation: Long-term (up to 2 years) clinical, angiographic, and intravascular ultrasound follow-upCirculation10616101613Google Scholar
  6. 6.
    Janero, DR, Ewing, JF 2000Nitric oxide and postangioplasty restenosis: Pathological correlates and therapeutic potentialFree Radic Biol Med2911991211PubMedGoogle Scholar
  7. 7.
    Beak, SH, Hrabie, JA, Keefer, LK,  et al. 2002Augmentation of intrapericardial nitric oxide level by a prolonged release NO donor reduces luminal narrowing after porcine coronary angioplastyCirculation10527782784Google Scholar
  8. 8.
    Hou, D, Rogers, PI, Toleikis, PM,  et al. 2000Intrapericardial space delivery of paclitaxel inhibits neointimal proliferation and promotes arterial enlargement after porcine coronary overstretchCirculation10215751581Google Scholar
  9. 9.
    Schwartz, RS, Huber, KC, Murphy, JG,  et al. 1992Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine modelJ Am Coll Cardiol19257275Google Scholar
  10. 10.
    Farb, A, Heller, PF, Shroff, S,  et al. 2001Pathological analysis of local delivery of paclitaxel via a polymer-coated stentCirculation104473479Google Scholar
  11. 11.
    Nathan, C, Xie, QW 1994Nitric oxide synthases: Roles, tolls, and controlsCell78915918CrossRefPubMedGoogle Scholar
  12. 12.
    Janero, DR, Ewing, JF 2000Nitric oxide and postangioplasty restenosis: Pathological correlates and therapeutic potentialFree Radic Biol Med2911991211PubMedGoogle Scholar
  13. 13.
    Rosanio, S, Tocchi, M, Patterson, C,  et al. 1999Prevention of restenosis after percutaneous coronary interventions: The medical approachThromb Haemost82164170PubMedGoogle Scholar
  14. 14.
    Faraci, FM, Sigmund, CD 1999Vascular biology in genetically altered mice: Smaller vessels, bigger insightCirc Res8512141225PubMedGoogle Scholar
  15. 15.
    Rolland, PH, Bartoli, JM, Piquet, P,  et al. 2002Local delivery of NO-donor molsidomine post-PTA improves haemodynamics, wall mechanics and histomorphometry in atherosclerotic porcine SFAEur J Vasc Endovasc Surg23226233PubMedGoogle Scholar
  16. 16.
    Maffia, P, Ianaro, A, Sorrentino, R,  et al. 2002Beneficial effects of NO-releasing derivative of flurbiprofen (HCT-1026) in rat model of vascular injury and restenosisArterioscler Thromb Vasc Biol22263267PubMedGoogle Scholar
  17. 17.
    Napoli, C, Aldini, G, Wallace, JL,  et al. 2002Efficacy and age-related effects of nitric oxide-releasing aspirin on experimental restenosisProc Natl Acad Sci USA9916891694Google Scholar
  18. 18.
    Varenne, O, Pislaru, S, Gillijns, H,  et al. 1998Local adenovirus-mediated transfer of human endothelial nitric oxide synthase reduces luminal narrowing after coronary angioplasty in pigsCirculation98919926Google Scholar
  19. 19.
    Cejna, M, Virmani, R, Jones, R,  et al. 2001Biocompatibility and performance of the Wallstent and several covered stents in a sheep iliac artery modelJ Vasc Interv Radiol12351358PubMedGoogle Scholar
  20. 20.
    Cejna, M, Virmani, R, Jones, R,  et al. 2002Biocompatibility and performance of the Wallstent and the Wallgraft, Jostent, and Hemobahn stent-grafts in a sheep modelJ Vasc Interv Radiol13823830PubMedGoogle Scholar
  21. 21.
    Yee, DC, Williams, SK, Salzmann, DL,  et al. 1998Stent versus endovascular graft healing characteristics in the porcine iliac arteryJ Vasc Interv Radiol9609617PubMedGoogle Scholar
  22. 22.
    Virmani, R, Kolodgie, FD, Dake, MD,  et al. 1999Histopathologic evaluation of an expanded polytetrafluoroethylene-nitinol stent endoprosthesis in canine iliofemoral arteriesJ Vasc Interv Radiol10445456PubMedGoogle Scholar
  23. 23.
    Yoon, JH, Wu, CJ, Homme, J,  et al. 2002Local delivery of nitric oxide from an eluting stent to inhibit neointimal thickening in a porcine coronary injury modelYonsei Med J43242251PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2004

Authors and Affiliations

  • Dongming Hou
    • 1
    • 3
    Email author
  • Hugh Narciso
    • 2
  • Kirti Kamdar
    • 2
  • Ping Zhang
    • 1
  • Bruce Barclay
    • 2
  • Keith L. March
    • 1
  1. 1.Indiana University School of MedicineIndianapolisUSA
  2. 2.Vascular Architects Inc.San JoseUSA
  3. 3.Indiana Center for Vascular Biology and MedicineKrannert Institute of CardiologyIndianapolisUSA

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