Abstract
Background
The major drawback of stent implantation in native human coronary vessels is the occurrence of restenosis. Drug-eluting stents significantly reduce restenosis after percutaneous coronary intervention (PCI), but may be associated with persistent local inflammation involved in the restenosis mechanisms. In this setting coating coronary devices with anti-inflammatory agents represents an intriguing alternative to stent-based local drug delivery. The aim of the present study was to test in a porcine model the safety and efficacy of a novel Genistein-eluting balloon preceding coronary stenting.
Design
Female piglets underwent PCI in a randomized fashion with either a Genistein-eluting or a standard balloon angioplasty, followed in all vessels by bare-metal stent implantation. Pigs were sacrificed at different time points to appraise safety (i.e. endothelialization) and efficacy (i.e. anti-inflammatory and anti-proliferative effects): 1, 4, and 6–8 weeks following PCI.
Results
Overall analysis was conducted on 14 piglets. Twenty-five bare-metal stents were implanted preceded by angioplasty with a conventional balloon in 13 vessels and by the Genistein-eluted balloon in 12. No untoward effects were reported in either group. Healing and endothelialization appeared universal within 4 weeks. The Genistein-eluted balloon group disclosed a significant reduction, at four weeks from implantation, of the peri-stent inflammatory cells count (mononucleocytes 39 ± 32 Vs. 96 ± 29 per square millimetre, P = 0.019). This effect did not clearly translate into a trend towards a reduced neointimal hyperplasia at 6–8 weeks (0.13 ± 0.11 Vs. 0.14 ± 0.09, P = 0.835).
Conclusion
This study provides the first in vivo demonstration of the anti-inflammatory effects of a Genistein-eluting balloon in PCI, warranting further research including the combination of a Genistein-eluting balloon with standard drug-eluting stent.
Similar content being viewed by others
References
Beier F, Gyöngyösi M, Raeder T, von Eckardstein-Thumb E, Sperker W, Albrecht P, Spes C, Glogar D, Mudra H (2006) First in-human randomized comparison of an anodized niobium stent versus a standard stainless steel stent—an intravascular ultrasound and angiographic two-center study: the VELA study. Clin Res Cardiol 95(9):455–460
Carlsson J, von Wagenheim B, Linder R, Anwari TM, Qvist J, Petersson I, Magounakis T, Lagerqvist B (2007) Is late stent thrombosis in drug-eluting stents a real clinical issue? A single-center experience and review of the literature. Clin Res Cardiol 96(2):86–93
Cook S, Walker A, Hügli O, Togni M, Meier B (2007) Percutaneous coronary interventions in Europe: prevalence, numerical estimates, and projections based on data up to 2004. Clin Res Cardiol 96(6):375–382
Dussaillant GR, Mintz GS, Pichard A, et al (1995) Small stent size and intimal hyperplasia contribute to restenosis: a volumetric intravascular ultrasound analysis. J Am Coll Cardiol 26:720–724
Gordon PC, Gibson M, Cohen DJ, Carroza JP, Kuntz RE, Baim DS (1993) Mechanisms of restenosis and redilation within coronary stents-quantitative angiographic assessment. J Am Coll Cardiol 21:1166–1174
Hoffman R, Mintz GS, Dussaillant GR, et al (1996) Patterns and mechanisms of instent restenosis: a serial intravascular ultrasound study. Circulation 94:1247–1254
Kammler J, Hofmann R, Steinwender C, Kypta A, Leisch F (2006) Simultaneous angiographic late stent thrombosis in two different coronary vessels after withdrawal of the combined anti-platelet therapy. Clin Res Cardiol 95(10):560–564
Karas SP, Gravanis MB, Santoian EC, Robinson KA, Anderberg KA, King SB III (1992) Coronary intimal proliferation after balloon injury and stenting in swine: an animal model of restenosis. J Am Coll Cardiol 20:467–474
Kornowski R, Hong MK, Tio FO, Bramwell O, Wu H, Leon MB (1998) In-stent restenosis: contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 31:224–230
Kuiper GG, Lemmen JG, Carlsson B, Corton JC, Safe SH, van der Saag PT, van der Burg B, Gustafsson JA (1998) Interaction of estrogenic chemicals and phytoestrogens with estrogen receptor beta. Endocrinology 139:4252–4263
Kuntz RE, Baim DS (2000) Prevention of coronary restenosis: the evolving evidence base for radiation therapy. Circulation 101:2130–2133
Lansky AJ, Costa RA, Mintz GS, Tsuchiya Y, Midei M, Cox DA, et al (2004) Nonpolymer-based paclitaxel-coated coronary stents for the treatment of patients with de novo coronary lesions: angiographic follow-up of the deliver clinical trial. Circulation 109:1948–1954
Libby P, Schwartz E, Brogi H, Tanaka H, Clinton SK (1992) A cascade model for restenosis: a special case of atherosclerosis progression. Circulation 86(Suppl III):47–52
Lincoff AM, Topol EJ, Ellis SG (1994) Local drug delivery for the prevention of restenosis: fact, fancy, and future. Circulation 90:2070–2082
Lowe HC, Schwartz RS, Mac Neill BD (2003) The porcine coronary model of instent restenosis: current status in the era of drug-eluting stents. Catheter Cardiovasc Interv 60:515–523
Moses JW, Leon MB, Popma JJ, et al (2003) Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N Engl J Med 349:1315–1323
Nakatani M, Takeyama Y, Shibata M, Yorozuya M, Suzuki H, Koba S, Katagiri T (2003) Mechanisms of restenosis after coronary intervention: difference between plain old balloon angioplasty and stenting. Cardiovasc Pathol 12:40–48
Nelson SR, Chien T, Di Salvo J (1997) Genistein sensitivity of calcium transport pathways in serotonin-activated vascular smooth muscle cells. Arch Biochem Biophys 345(1):65–72
Park SJ, Shim WH, Ho DS, et al (2003) A paclitaxel-eluting stent for the prevention of coronary restenosis. N Engl J Med 348:1537–1545
Ribichini F, Joner M, Ferrero V, Finn AV, Crimins J, Nakazawa G, Acampado E, Kolodgie FD, Vassanelli C, Virmani R (2007) Effects of oral prednisone after stenting in a rabbit model of established atherosclerosis. J Am Coll Cardiol 50:176–185
Ribichini F, Tomai F, Paloscia L, Di Sciascio G, Carosio G, Romano M, Verna E, Galli M, Tamburino C, De Cesare M, Pirisi R, Piscione F, Lanteri G, Ferrero V, Vassanelli C (2007) Steroid-eluting stents in patients with acute coronary syndrome: the dexamethasone eluting stent Italian registry. Heart 93(5):598–600
Schatz RA, Palmaz JC, Tio F, Garcia F, Garcia O, Reuter SR (1987) Balloon expandable intracoronary stents in the adult dog. Circulation 76:450–457
Scheller B, Hehrlein C, Bocksch W, Rutsch W, Haghi D, Dietz U, Böhm M, Speck U (2006) Treatment of in-stent restenosis with a paclitaxel-coated balloon catheter. New Engl J Med 355:2113–2124
Scheller B, Speck U, Abramjuk C, Bernhardt U, Bohm M, Nickenig G (2004) Paclitaxel balloon coating: a novel method for prevention and therapy of restenosis. Circulation 110:810–814
Scheller B, Speck U, Schmitt A, Bohm M, Nickenig G (2003) Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation. J Am Coll Cardiol 42(8):1415–1420
Scheller B, Speckb U, Romeikec B, Schmitta A, Sovakd M, Böhma M, Stolla HP (2003) Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model. Eur Heart J 24:1462–1467
Schwartz RS, Chronos NA, Virmani R (2004) Preclinical restenosis models and drug-eluting stents. still important, still much to learn. J Am Coll Cardiol 44:1373–1385
Schwartz R, Huber K, Murphy J, et al (1992) Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. J Am Coll Cardiol 19:267–274
Schwartz RS, Murphy JG, Edwards WD, Camrud AR, Vliestra RE, Holmes DR (1990) Restenosis after balloon angioplasty: a practical proliferative model in porcine coronary arteries. Circulation 82:2190–2200
Schwartz RS, Topol EJ, Serruys PW, Sangiorgi G, Holmes DR Jr (1998) Artery size, neointima, and remodeling: time for some standards. J Am Coll Cardiol 32:2087–2094
Si H, Liu D (2007) Phytochemical genistein in the regulation of vascular function: new insights. Curr Med Chem 14(24):2581–2589
Speck U, Scheller B, Abramjuk C, Breitwieser C, Dobberstein J, Boehm M, Hamm B (2006) Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. Radiology 240:411–418
Speck U, Scheller B, Abramjuk C, Grossmann S, Mahnkopf D, Simon O (2004) Inhibition of restenosis in stented porcine coronary arteries: uptake of paclitaxel from angiographic contrast media. Invest Radiol 39:182–186
Tanabe K, Regar E, Lee CH, Hoye A, van der Giessen WJ, Serruys W (2004) Local drug delivery using coated stents: new developments and future perspectives. Curr Pharm Des 10:357–367
Tanaka H, Sukhova GK, Swanson SJ, et al (1993) Sustained activation of vascular cells and leukocytes in the rabbit aorta after balloon injury. Circulation 88:1788–1803
Versaci F, Gaspardone A, Tomai F, et al (2002) Immunosuppressive therapy for the prevention of restenosis after coronary artery stent implantation (IMPRESS study). J Am Coll Cardiol 40:1935–1942
Virmani R, Kolodgie FD, Farb A, Lafont A (2003) Drug eluting stents: are human and animal studies comparable? Heart 89:133–138
Voisard R, Seitzer U, Baur R, et al (1994) Corticosteroid agents inhibit proliferation of smooth muscle cells from human atherosclerotic arteries in vitro. Int J Cardiol 43:257–267
Wöhrle J, Nusser T, Kestler HA, Kochs M, Hombach V (2007) Comparison of the slow-release polymer-based paclitaxel-eluting taxus-express stent with the bare-metal express stent for saphenous vein graft interventions. Clin Res Cardiol 96(2):70–76
Zahn R, Hamm CW, Schneider S, Zeymer U, Richardt G, Kelm M, Levenson B, Bonzel T, Tebbe U, Sabin G, Nienaber CA, Pfannebecker T, Senges J (2007) The Sirolimus-eluting coronary stent in daily routine practice in Germany: trends in indications over the years. Results from the prospective multi-centre German cypher stent registry. Clin Res Cardiol 96(8):548–556
Acknowledgments
Funding: Sahajanand Medical Technologies Pvt. Ltd (unrestricted grant to IS). Conflict of interest: None declared.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sheiban, I., Anselmino, M., Moretti, C. et al. Effect of a novel drug-eluted balloon coated with Genistein before stent implantation in porcine coronary arteries. Clin Res Cardiol 97, 891–898 (2008). https://doi.org/10.1007/s00392-008-0705-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00392-008-0705-2