Abstract
The objective of this study was to evaluate the efficacy of heparin-polymer-coated intravascular stents in the reduction of vessel stenosis. Three types of coatings for Palmaz stents were tested: 1) heparin covalently bound to a polyethylene oxide (Hp-PEO) tether; 2) heparin copolymerized with ethylene vinyl acetate (Hp-Elvax) and 3) Elvax alone. Polymer-coated stents and uncoated controls were deployed in the external iliac arteries following endothelial injury in 18 swine. The animals were maintained on an atherogenic diet and examined by angiography at 6 and 12 weeks. The stented segments were then harvested for histopathologic analysis. Both types of heparin-coated stents resulted in increased luminal narrowing as compared to the contralateral uncoated stents. At 6 weeks, average luminal stenosis was 48% for Hp-PEO stents vs 35% for uncoated stents (p < 0.05). At 12 weeks, average luminal stenosis was 36% for Hp-PEO stents vs 26% for uncoated stents (p = NS). For Hp-Elvax stents, the average stenosis was 58% vs 33% for uncoated controls (p < 0.05) at 6 weeks and 47% vs 19% for uncoated controls (p < 0.05) at 12 weeks. There was no significant difference between Hp-Elvax stents and Elvax stents (p = NS). Increased luminal narrowing in coated stents was primarily secondary to a marked inflammatory response. Heparin-polyethylene oxide and heparin-ethylene vinyl acetate-coated stents resulted in increased luminal narrowing as compared with uncoated stents, due to a marked inflammatory response.
Similar content being viewed by others
References
M Haude R Erbel H Issa J Meyer (1993) ArticleTitleQuantitative analysis of elastic recoil after balloon angioplasty and after intracoronary implantation of balloon-expandable Palmaz-Schatz stents. J Am Coll Cardiol 21 IssueID1 26–34 Occurrence Handle8417068
JB Foley RI Brown IM Penn (1994) ArticleTitleThrombosis and restenosis after stenting in failed angioplasty: Comparison with elective stenting. Am Heart J 128 IssueID1 12–20 Occurrence Handle8017264
LM Hennequin FG Joffre HP Rousseau R Aziza P Tregant P Bernadet M Salvador B Chamontin (1994) ArticleTitleRenal artery stent placement: Long-term results with the Wallstent endoprosthesis. Radiology 191 IssueID3 713–719 Occurrence Handle8184051
PP de Jaegere WR Hermans BJ Rensing BH Strauss PJ deFeyter PW Serruys (1993) ArticleTitleMatching based on quantitative coronary angiography as a surrogate for randomized studies: Comparison between stent implantation and balloon angioplasty of native coronary artery lesions. Am Heart J 125 IssueID2 Pt 1 310–319 Occurrence Handle8427121
DL Fischman MB Leon DS Baim et al. (1994) ArticleTitleA randomized comparison of coronary-stent placement and balloon angioplasty in the treatment of coronary artery disease. Stent Restenosis Study Investigators. N Engl J Med 331 IssueID8 496–501 Occurrence Handle1:STN:280:ByuA3MnisFQ%3D Occurrence Handle8041414
PW Serruys P de Jaegere F Kiemeneij et al. (1994) ArticleTitleA comparison of balloon-expandable stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. N Engl J Med 331 IssueID8 489–495
RS Schwartz KC Huber JG Murphy WD Edwards AR Camrud RE Vliestra DR Holmes (1992) ArticleTitleRestenosis and the proportional neointimal response to coronary artery injury: Results in a porcine model. J Am Coll Cardiol 19 IssueID2 267–274 Occurrence Handle1:STN:280:By2C387ls1A%3D Occurrence Handle1732351
R Kornowski MK Hong FO Tio O Bramwell H Wu MB Leon (1998) ArticleTitleIn-stent restenosis: Contributions of inflammatory responses and arterial injury to neointimal hyperplasia. J Am Coll Cardiol 31 IssueID1 224–230 Occurrence Handle1:STN:280:DyaK1c%2Fos1SisQ%3D%3D Occurrence Handle9426044
WJ van der Geissen AM Lincoff RS Schwartz HM van Beusekom PW Serruys DR Jr Holmes SG Ellis EJ Topol (1996) ArticleTitleMarked inflammatory sequelae to implantation of biodegradable and nonbiodegradable polymers in porcine coronary arteries. Circulation 94 IssueID7 1690–1697 Occurrence Handle8840862
M Back G Kopchok M Mueller D Cavaye C Donayre RA White (1994) ArticleTitleChanges in arterial wall compliance after endovascular stenting. J Vasc Surg 19 IssueID5 905–911 Occurrence Handle8170046
D Vorwerk F Redha J Neuerburg C Clerc RW Gunther (1994) ArticleTitleNeointimal formation following arterial placement of self-expanding stents of different radial force: Experimental results. Cardiovasc Intervent Radiol 17 IssueID1 27–32
C Chuapetcharasopon KC Wright S Wallace RL Dobben C Gianturco (1992) ArticleTitleTreatment of experimentally induced atherosclerosis in swine iliac arteries: A comparison of self-expanding and balloon-expanded stents. Cardiovasc Intervent Radiol 15 IssueID3 143–50 Occurrence Handle1628279
AB Buchwald C Unterberg K Nebendahl HJ Grone V Wiegard (1992) ArticleTitleLow-molecular-weight heparin reduces neointimal proliferation after coronary stent implantation in hypercholesterolemic minipigs. Circulation 86 IssueID2 531–537 Occurrence Handle1322255
A Kastrati A Schomig R Dietz FJ Neumann G Richardt (1993) ArticleTitleTime course of restenosis during the first year after emergency coronary stenting. Circulation 87 IssueID5 1498–1505 Occurrence Handle8491004
MC Bourin U Lindahl (1993) ArticleTitleGlycosaminoglycans and the regulation of blood coagulation. Biochem J 289 IssueID2 313–330 Occurrence Handle8380990
U Lindahl K Lidholt D Spillmann L Kjellen (1994) ArticleTitleMore to “heparin” than anticoagulation. Thromb Res 75 IssueID1 1–32 Occurrence Handle8073404
ER Edelman DH Adams MJ Karnovsky (1990) ArticleTitleEffect of controlled adventitial heparin delivery on smooth muscle cell proliferation following endothelial injury. Proc Natl Acad Sci USA 87 IssueID10 3773–3777 Occurrence Handle2339120
T Okada DH Bark MR Mayberg (1989) ArticleTitleLocalized release of perivascular heparin inhibits intimal proliferation after endothelial injury without systemic anticoagulation. Neurosurgery 25 IssueID6 892–898
G. Di Colo (1992) ArticleTitleControlled drug release from implantable matrices based on hydrophobic polymers. Biomaterials 13 IssueID12 850–856 Occurrence Handle1457678
Langer R, Folkman J (1976) Polymers for the sustained release of proteins and other macromolecules. Nature 263(5580):797–800
C Nojiri KD Park DW Grainger HA Jacobs T Okano H Koyanagi SW Kim (1990) ArticleTitleIn vivo nonthrombogenicity of heparin immobilized polymer surfaces. ASAIO Trans 36 IssueID3 M168–172 Occurrence Handle2252651
WG Kim KD Park SF Mohammad SW Kim (1991) ArticleTitleSPUU-PEO-heparin graft copolymer surfaces. Patency and platelet deposition in canine small diameter arterial grafts. ASAIO Trans 37 IssueID3 M148–M149 Occurrence Handle1751086
PA Hardhammar HM van Beusekom HU Emanuelsson SH Hofma PA Albertsson PD Verdouw E Boersma PW Serruys WJ. van der Giessen (1996) ArticleTitleReduction in thrombotic events with heparin-coated Palmaz-Schatz stents in normal porcine coronary arteries. Circulation 93 IssueID3 423–430 Occurrence Handle8565158
YK Ahn MH Jeong JW Kim SH Kim JH Cho JG Cho CS Park SW Juhng JC Park JC Kang (1999) ArticleTitlePreventive effects of the heparin-coated stent on restenosis in the porcine model. Cathet Cardiovasc Intervent 48 IssueID3 324–330 Occurrence Handle10.1002/(SICI)1522-726X(199911)48:3<324::AID-CCD20>3.0.CO;2-K
PW Serruys H Emanuelsson W van der Giessen AC Lunn F Kiemeney C Macaya W Rutsch G Heyndrickx H Suryapranata V Legrand JJ Goy P Materne H Bonnier MC Morice J Fajadet J Belardi A Colombo E Garcia P Ruygrok P de Jaegere MA Morel (1996) ArticleTitleHeparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcome of the Benestent-II Pilot Study. Circulation 93 IssueID3 412–422 Occurrence Handle8565157
PW Serruys B van Hout H Bonnier V Legrand E Garcia C Macaya E Sousa W van der Giessen A Colombo R Seabra-Gomes F Kiemeneij P Ruygrok J Ormiston H Emanuelsson J Fajadet M Haude S Klugmann MA Morel (1998) ArticleTitleRandomized comparison of implantation of heparin-coated stents with balloon angioplasty in selected patients with coronary artery disease (Benestent II). Lancet 352 IssueID9129 673–681 Occurrence Handle1:STN:280:DyaK1czpslWquw%3D%3D Occurrence Handle9728982
AZ Piao C Nojiri KD Park H Jacobs J Feijen SW Kim (1990) ArticleTitleSynthesis and characterization of poly(dimethylsioxane)-poly(ethylene oxide)-heparin CBABC type block copolymers. J Biomater Sci Polym Ed 1 IssueID4 299–313 Occurrence Handle2279007
KD Park WG Kim H Jacobs T Okano SW Kim (1992) ArticleTitleBlood compatibility of SPUU-PEO-heparin graft copolymers. J Biomed Mater Res 26 IssueID6 739–756 Occurrence Handle1527098
TE Brothers JG Robison BM Elliott JM Boggs AE Frankel MC Willingham (1995) ArticleTitleUpregulation of b-FGF receptor expression after carotid bypass. J Surg Res 58 IssueID1 28–32 Occurrence Handle10.1006/jsre.1995.1005 Occurrence Handle7830402
JM Herbert A Tissinier G Defreyn JP Maffrand (1993) ArticleTitleInhibitory effect of clopidogrel on platelet adhesion and intimal proliferation after arterial injury in rabbits. Arterioscler Thromb 13 IssueID8 1171–1179 Occurrence Handle8343491
MA Levitt M Dryjski J Tluczek TD Bjornsson (1991) ArticleTitleEvaluation of prostacyclin analog, iloprost, and a thromboxane A2 receptor antagonist, daltroban, in experimental intimal hyperplasia. Prostaglandins 41 IssueID1 1–6 Occurrence Handle10.1016/0090-6980(91)90099-2
E Munro M Patel P Chan L Betteridge K Gallagher M Schachter J Wolfe P Sever (1994) ArticleTitleEffect of calcium channel blockers on the growth of human vascular smooth muscle cells derived from saphenous vein and vascular graft stenoses. J Cardiovasc Pharmacol 23 IssueID5 779–784
MH Howell MM Adams MS Wolfe ML Foegh PW Ramwell (1993) ArticleTitleAngiopeptin inhibition of myointimal hyperplasia after balloon angioplasty of large arteries in hypercholesterolaemic rabbits. Clin Sci (Lond) 85 IssueID2 183–188
MK Hong T Bhatti BJ Matthews KS Stark SS Cathapermal ML Foegh PW Ramwell KM Kent (1993) ArticleTitleThe effect of porous infusion balloon-delivered angiopeptin on myointimal hyperplasia after balloon injury in the rabbit. Circulation 88 IssueID2 638–648 Occurrence Handle8101773
ML Foegh S Asotra MH Howell PW Ramwell (1994) ArticleTitleEstradiol inhibition of arterial neointimal hyperplasia after balloon injury. J Vasc Surg 19 IssueID4 722–726 Occurrence Handle7909339
H Rakugi JH Jacob JE Krieger JR Ingelfinger RE Pratt (1993) ArticleTitleVascular injury induces angiotensinogen gene expression in the media and neointimal. Circulation 87 IssueID1 283–290 Occurrence Handle8419017
P Janiak O Libert JP Vilaine (1994) ArticleTitleRole of the renin-angiotensin system in neointima formation after injury in rabbits. Hypertension 24 IssueID6 671–678 Occurrence Handle7995623
MD Colburn WS Moore HA Gelabert WJ. Quinones-Baldrich (1992) ArticleTitleDose-responsive suppression of myointimal hyperplasia by dexamethasone. J Vasc Surg 15 IssueID3 510–518 Occurrence Handle10.1067/mva.1992.32078 Occurrence Handle1538508
TA Fischell (1994) ArticleTitlePolymer coatings for stents: Can we judge a stent by its cover? Circulation 94 IssueID7 1494–1495
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Goodwin, S., Yoon, HC., Chen, G. et al. Intense Inflammatory Reaction to Heparin Polymer Coated Intravascular Palmaz Stents in Porcine Arteries Compared to Uncoated Palmaz Stents . CVIR 26, 158–167 (2003). https://doi.org/10.1007/s00270-002-2562-0
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00270-002-2562-0