Heart and Vessels

, Volume 32, Issue 10, pp 1244–1252 | Cite as

Early endothelialization associated with a biolimus A9 bioresorbable polymer stent in a porcine coronary model

  • Masayuki Mori
  • Kenji Sakata
  • Chiaki Nakanishi
  • Takuya Nakahashi
  • Masa-aki Kawashiri
  • Kazuaki Yoshioka
  • Yoh Takuwa
  • Hirofumi Okada
  • Jun-ichiro Yokawa
  • Masaya Shimojima
  • Tsuyoshi Yoshimuta
  • Shohei Yoshida
  • Masakazu Yamagishi
  • Kenshi Hayashi
Original Article

Abstract

Although Nobori®, with a bioresorbable polymer and biolimus A9 abluminal coating, has unique characteristics, few data exist regarding endothelialization early after implantation. Fifteen Nobori® and 14 control bare-metal stents (S-stent™) were implanted in 12 pigs. Histopathology of stented segments, inflammation, and intimal fibrin content was evaluated on the 2nd and 14th day after implantation. On the 2nd day, endothelial cells were morphologically and immunohistologically confirmed on the surface of both stents, although some inflammatory cells might be involved. Stent surface endothelialization evaluated with a scanning electron microscope showed partial cellular coverage in both stents. On the 14th day, neointimal thickness and percentage of the neointimal area were significantly lower in Nobori® than in S-stent™ (51.4 ± 4.5 vs. 76.4 ± 23.6 µm, p < 0.05 and 10.8 ± 2.6 vs. 14.1 ± 4.2%, p < 0.01). No significant differences were found in these parameters on the 2nd day (17.3 ± 14.9 vs. 26.7 ± 13.6 µm and 3.7 ± 3.0 vs. 6.7 ± 3.7%), in inflammatory and intimal fibrin content scores. These results demonstrate that endothelialization could occur early after Nobori® implantation with similar inflammatory reaction to bare-metal stents, probably contributing to low frequency of in-stent thrombosis and restenosis.

Keywords

Drug-eluting stent Endothelialization Bioresorbable polymer 

References

  1. 1.
    Versaci F, Gaspardone A, Tomai F, Crea F, Chiariello L, Gioffrè PA (1997) A comparison of coronary-artery stenting with angioplasty for isolated stenosis of the proximal left anterior descending coronary artery. N Engl J Med 336:817–822CrossRefPubMedGoogle Scholar
  2. 2.
    Grines CL, Cox DA, Stone GW, Garcia E, Mattos LA, Giambartolomei A, Brodie BR, Madonna O, Eijgelshoven M, Lansky AJ, O’Neill WW, Morice MC (1999) Coronary angioplasty with or without stent implantation for acute myocardial infarction. Stent primary angioplasty in myocardial infarction study group. N Engl J Med 341:1949–1956CrossRefPubMedGoogle Scholar
  3. 3.
    Uchiyama K, Ino H, Hayashi K, Fujioka K, Takabatake S, Yokawa J, Namura M, Mizuno S, Tatami R, Kanaya H, Nitta Y, Michishita I, Hirase H, Ueda K, Aoyama T, Okeie K, Haraki T, Mori K, Araki T, Minamoto M, Oiwake H, Konno T, Sakata K, Kawashiri M, Yamagishi M (2011) Impact of severe coronary disease associated or not associated with diabetes mellitus on outcome of interventional treatment using stents: results from HERZ (Heart Research Group of Kanazawa) analyses. J Int Med Res 39:549–557CrossRefPubMedGoogle Scholar
  4. 4.
    Kastrati A, Dibra A, Mehilli J, Mayer S, Pinieck S, Pache J, Dirschinger J, Schömig A (2006) Predictive factors restenosis after coronary implantation of sirolimus- or paclitaxel-eluting stents. Circulation 113:2293–2300CrossRefPubMedGoogle Scholar
  5. 5.
    Serruys PW, Kutryk MJ, Ong AT (2006) Coronary-artery stents. N Engl J Med 354:483–495CrossRefPubMedGoogle Scholar
  6. 6.
    Yoshida T, Sakata K, Nitta Y, Taguchi T, Kaku B, Katsuda S, Shimojima M, Gamou T, Nakahashi T, Konno T, Kawashiri MA, Yamagishi M, Hayashi K (2015) Short- and long-term benefits of drug-eluting stents compared to bare metal stents even in treatment for large coronary arteries. Heart Vessels 31:635–642CrossRefPubMedGoogle Scholar
  7. 7.
    Kawashiri MA, Sakata K, Uchiyama K, Konno T, Namura M, Mizuno S, Tatami R, Kanaya H, Nitta Y, Michishita I, Hirase H, Ueda K, Aoyama T, Okeie K, Haraki T, Mori K, Araki T, Minamoto M, Oiwake H, Ino H, Hayashi K, Yamagishi M (2014) Impact of lesion morphology and associated procedures for left main coronary stenting on angiographic outcome after intervention: sub-analysis of Heart Research Group of Kanazawa, HERZ, Study. Cardiovasc Interv Ther 29:117–122CrossRefPubMedGoogle Scholar
  8. 8.
    Kobayashi N, Ito Y, Hirano K, Yamawaki M, Araki M, Sakai T, Takimura H, Sakamoto Y, Mori S, Tsutsumi M, Takama T, Takafuji H, Maruyama T, Honda Y, Tokuda T, Makino K, Shirai S, Muramatsu T (2016) Comparison of first- and second-generation drug-eluting stent efficacies for treating left main and/or three-vessel disease: a propensity matched study. Heart Vessels 31:1930–1942CrossRefPubMedGoogle Scholar
  9. 9.
    Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E, Kutys R, Skorija K, Gold HK, Virmani R (2006) Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. J Am Coll Cardiol 48:193–202CrossRefPubMedGoogle Scholar
  10. 10.
    Cook S, Ladich E, Nakazawa G, Eshtehardi P, Neidhart M, Vogel R, Togni M, Wenaweser P, Billinger M, Seiler C, Gay S, Meier B, Pichler WJ, Jüni P, Virmani R, Windecker S (2009) Correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis. Circulation 120:391–399CrossRefPubMedGoogle Scholar
  11. 11.
    Sakata K, Namura M, Takagi T, Tama N, Inoki I, Terai H, Horita Y, Ikeda M, Yamagishi M (2015) Repeated occurrence of slow flow phenomenon during and late after sirolimus-eluting stent implantation. Heart Vessels 30:406–409CrossRefPubMedGoogle Scholar
  12. 12.
    Kurosawa T, Kotani J, Matsuyama TA, Ishibashi-Ueda H (2015) A case of active peri-stent inflammation after sirolimus-eluting stent implantation. Heart Vessels 30:270–273CrossRefPubMedGoogle Scholar
  13. 13.
    Finn AV, Joner M, Nakazawa G, Kolodgie F, Newell J, John MC, Gold HK, Virmani R (2007) Pathological correlates of late drug-eluting stent thrombosis: strut coverage as a marker of endothelialization. Circulation 115:2435–2441CrossRefPubMedGoogle Scholar
  14. 14.
    Pfisterer M, Brunner-La Rocca HP, Buser PT, Rickenbacher P, Hunziker P, Mueller C, Jeger R, Bader F, Osswald S, Kaiser C, Investigators BASKET-LATE (2006) Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents. J Am Coll Cardiol 48:2584–2591CrossRefPubMedGoogle Scholar
  15. 15.
    Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T, Mihalcsik L, Tespili M, Valsecchi O, Kolodgie FD (2004) Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? Circulation 109:701–705CrossRefPubMedGoogle Scholar
  16. 16.
    Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J, Davidson CJ, McKoy JM, Raisch DW, Whisenant BK, Yarnold PR, Belknap SM, West DP, Gage JE, Morse RE, Gligoric G, Davidson L, Feldman MD (2006) Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and reports (RADAR) project. J Am Coll Cardiol 47:175–181CrossRefPubMedGoogle Scholar
  17. 17.
    Chevalier B, Silber S, Park SJ, Garcia E, Schuler G, Suryapranata H, Koolen J, Hauptmann KE, Wijns W, Morice MC, Carrie D, van Es GA, Nagai H, Detiege D, Paunovic D, Serruys PW, NOBORI 1 Clinical Investigators (2009) Randomized comparison of the Nobori Biolimus A9-eluting coronary stent with the Taxus Liberte paclitaxel-eluting coronary stent in patients with stenosis in native coronary arteries: the NOBORI 1 trial—phase 2. Circ Cardiovasc Interv 2:188–195CrossRefPubMedGoogle Scholar
  18. 18.
    Nishimiya K, Matsumoto Y, Shindo T, Hanawa K, Hasebe Y, Tsuburaya R, Shiroto T, Takahashi J, Ito K, Ishibashi-Ueda H, Yasuda S, Shimokawa H (2015) Association of adventitial vasa vasorum and inflammation with coronary hyperconstriction after drug-eluting stent implantation in pigs in vivo. Circ J 79:1787–1798CrossRefPubMedGoogle Scholar
  19. 19.
    Serruys PW, Farooq V, Kalesan B, de Vries T, Buszman P, Linke A, Ischinger T, Klauss V, Eberli F, Wijns W, Morice MC, Di Mario C, Corti R, Antoni D, Sohn HY, Eerdmans P, Rademaker-Havinga T, van Es GA, Meier B, Jüni P, Windecker S (2013) Improved safety and reduction in stent thrombosis associated with biodegradable polymer-based biolimus-eluting stents versus durable polymer-based sirolimus-eluting stents in patients with coronary artery disease: final 5-year report of the LEADERS (Limus Eluted From A Durable Versus ERodable Stent Coating) randomized, noninferiority trial. JACC Cardiovasc Interv 6:777–789CrossRefPubMedGoogle Scholar
  20. 20.
    Natsuaki M, Kozuma K, Morimoto T, Kadota K, Muramatsu T, Nakagawa Y, Akasaka T, Igarashi K, Tanabe K, Morino Y, Ishikawa T, Nishikawa H, Awata M, Abe M, Okada H, Takatsu Y, Ogata N, Kimura K, Urasawa K, Tarutani Y, Shiode N, Kimura T (2013) Biodegradable polymer biolimus-eluting stent versus durable polymer everolimus-eluting stent: a randomized, controlled, noninferiority trial. J Am Coll Cardiol 62:181–190CrossRefPubMedGoogle Scholar
  21. 21.
    Christiansen EH, Jensen LO, Thayssen P, Tilsted HH, Krusell LR, Hansen KN, Kaltoft A, Maeng M, Kristensen SD, Bøtker HE, Terkelsen CJ, Villadsen AB, Ravkilde J, Aarøe J, Madsen M, Thuesen L, Lassen JF (2013) Biolimus-eluting biodegradable polymer-coated stent versus durable polymer-coated sirolimus-eluting stent in unselected patients receiving percutaneous coronary intervention (SORT OUT V): a randomised non-inferiority trial. Lancet 381:661–669CrossRefPubMedGoogle Scholar
  22. 22.
    Takabatake S, Hayashi K, Nakanishi C, Hao H, Sakata K, Kawashiri MA, Matsuda T, Yamagishi M (2014) Vascular endothelial growth factor-bound stents: application of in situ capture technology of circulating endothelial progenitor cells in porcine coronary model. J Interv Cardiol 27:63–72CrossRefPubMedGoogle Scholar
  23. 23.
    Schwartz RS, Huber KC, Murphy JG, Edwards WD, Camrud AR, Vlietstra RE, Holmes DR (1992) Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. J Am Coll Cardiol 19:267–274CrossRefPubMedGoogle Scholar
  24. 24.
    Suzuki T, Kopia G, Hayashi S, Bailey LR, Llanos G, Wilensky R, Klugherz BD, Papandreou G, Narayan P, Leon MB, Yeung AC, Tio F, Tsao PS, Falotico R, Carter AJ (2001) Stent-based delivery of sirolimus reduces neointimal formation in a porcine coronary model. Circulation 104:1188–1193CrossRefPubMedGoogle Scholar
  25. 25.
    Sakata K, Waseda K, Kume T, Otake H, Nakatani D, Yock PG, Fitzgerald PJ, Honda Y (2012) Impact of diabetes mellitus on vessel response in the drug-eluting stent era: pooled volumetric intravascular ultrasound analyses. Circ Cardiovasc Interv 5:763–771CrossRefPubMedGoogle Scholar
  26. 26.
    Pearson JD (1994) Endothelial cell function and thrombosis. Baillieres Clin Haematol 7:441–452CrossRefPubMedGoogle Scholar
  27. 27.
    Carter AJ, Laird JR, Farb A, Kufs W, Wortham DC, Virmani R (1994) Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model. J Am Coll Cardiol 24:1398–1405CrossRefPubMedGoogle Scholar
  28. 28.
    Taylor AJ, Gorman PD, Kenwood B, Hudak C, Tashko G, Virmani R (2001) A comparison of four stent designs on arterial injury, cellular proliferation, neointima formation, and arterial dimensions in an experimental porcine model. Catheter Cardiovasc Interv 53:420–425CrossRefPubMedGoogle Scholar
  29. 29.
    Farb A, Sangiorgi G, Carter AJ, Walley VM, Edwards WD, Schwartz RS, Virmani R (1999) Pathology of acute and chronic coronary stenting in humans. Circulation 99:44–52CrossRefPubMedGoogle Scholar
  30. 30.
    Pendyala LK, Matsumoto D, Shinke T, Iwasaki T, Sugimoto R, Hou D, Chen JP, Singh J, King SB 3rd, Chronos N, Li J (2012) Nobori stent shows less vascular inflammation and early recovery of endothelial function compared with Cypher stent. JACC Cardiovasc Interv 5:436–444CrossRefPubMedGoogle Scholar
  31. 31.
    Nakazawa G, Shinke T, Ijichi T, Matsumoto D, Otake H, Torii S, Hiranuma N, Ohsue T, Otsuka F, Shite J, Hirata K, Ikari Y (2014) Comparison of vascular response between durable and biodegradable polymer-based drug-eluting stents in a porcine coronary artery model. EuroIntervention 10:717–723CrossRefPubMedGoogle Scholar
  32. 32.
    Hiranuma N, Shinke T, Nakazawa G, Otake H, Matsumoto D, Ijichi T, Kawamori H, Nagoshi R, Osue T, Shite J, Hirata K (2014) Optical coherence tomography and histopathology assessment after implantation of first- and second-generation drug-eluting stents in a porcine coronary model. Circ J 78(11):2665–2673CrossRefPubMedGoogle Scholar
  33. 33.
    Tagawa S, Matsuda T, Aomizu T, Kuwana M, Ohtake H, Watanabe G, Yamagishi M (2014) Surface-bound vascular endothelial growth factor promotes prolonged activation of endothelial cells: a new technology for capturing endothelial progenitor cells by intravascular stents. J Tissue Sci Eng 5:1000140. doi:10.4172/2157-7552.1000140 Google Scholar
  34. 34.
    Hagiwara H, Hiraishi Y, Terao H, Hirai T, Sakaoka A, Sasaki M, Murota S, Inoue K, Kimura J (2012) Vascular responses to a biodegradable polymer (polylactic acid) based biolimus A9-eluting stent in porcine models. EuroIntervention 8:743–751CrossRefPubMedGoogle Scholar

Copyright information

© Springer Japan 2017

Authors and Affiliations

  • Masayuki Mori
    • 1
  • Kenji Sakata
    • 1
  • Chiaki Nakanishi
    • 1
  • Takuya Nakahashi
    • 1
  • Masa-aki Kawashiri
    • 1
  • Kazuaki Yoshioka
    • 2
  • Yoh Takuwa
    • 2
  • Hirofumi Okada
    • 1
  • Jun-ichiro Yokawa
    • 1
  • Masaya Shimojima
    • 1
  • Tsuyoshi Yoshimuta
    • 1
  • Shohei Yoshida
    • 1
  • Masakazu Yamagishi
    • 1
  • Kenshi Hayashi
    • 1
  1. 1.Department of Cardiovascular and Internal MedicineKanazawa University Graduate School of MedicineKanazawaJapan
  2. 2.Department of Molecular Vascular PhysiologyKanazawa University Graduate School of MedicineKanazawaJapan

Personalised recommendations