Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: Prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours

Mariann Gyöngyösi; Christoph Strehblow; Wolfgang Sperker; Akos Hevesi; Rita Garamvölgyi; Zsolt Petrási; Noemi Pavo; Péter Ferdinandy; Csaba Csonka; Tamás Csont; Christer Sylvén; Paul J. Declerck; Pavo Imre Jr.; Johann Wojta; Dietmar Glogar; Kurt Huber

doi:10.1160/TH06-03-0178

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2006; 96(02): 202-209
DOI: 10.1160/TH06-03-0178

Animal Models

Schattauer GmbH

Platelet activation and high tissue factor level predict acute stent thrombosis in pig coronary arteries: Prothrombogenic response of drug-eluting or bare stent implantation within the first 24 hours

Authors

Mariann Gyöngyösi

¹Department of Cardiology, Medical University of Vienna, Vienna, Austria
Christoph Strehblow

¹Department of Cardiology, Medical University of Vienna, Vienna, Austria
Wolfgang Sperker

¹Department of Cardiology, Medical University of Vienna, Vienna, Austria
Akos Hevesi

²Institute of Diagnostic Imaging and Radiation Oncology, University of Kaposvar, Kaposvar Hungary
Rita Garamvölgyi

²Institute of Diagnostic Imaging and Radiation Oncology, University of Kaposvar, Kaposvar Hungary
Zsolt Petrási

²Institute of Diagnostic Imaging and Radiation Oncology, University of Kaposvar, Kaposvar Hungary
Noemi Pavo

¹Department of Cardiology, Medical University of Vienna, Vienna, Austria
Péter Ferdinandy

³Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary
Csaba Csonka

³Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary
Tamás Csont

³Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Hungary
Christer Sylvén

⁴Department of Cardiology, Karolinska University Hospital at Huddinge, Karolinska Institutet, Stockholm, Sweden
Paul J. Declerck

⁵Laboratory for Pharmaceutical Biology and Phytopharmacology, Faculty of Pharmaceutical Sciences, Katholieke Universiteit Leuven, Belgium
Pavo Imre Jr.

¹Department of Cardiology, Medical University of Vienna, Vienna, Austria
Johann Wojta

¹Department of Cardiology, Medical University of Vienna, Vienna, Austria
Dietmar Glogar

¹Department of Cardiology, Medical University of Vienna, Vienna, Austria
Kurt Huber

⁶3rd Department of Medicine, Cardiology and Emergency Medicine, Wilhelminenhospital, Vienna, Austria

Abstract

Summary

Increased thrombogenicity of drug-eluting stents (DESs) has recently been reported.The aim of the present study was to investigate the prothrombogenic effect of DESs and Bare stents, and determine factors predictive of acute stent thrombosis (AST) in preclinical experiments using new stent design or coating.Circulating preand post-stenting parameters of platelet activation (mean platelet volume, MPV; platelet distribution width, platelet large cell ratio), thrombin activation (thrombin-antithrombin complex, TAT and prothrombin fragments, F1+2), tissue factor antigen (TF-ag) and -activity (TF-act) and plasminogen activator inhibitor-1 (PAI-1) were measured in 141 consecutive pigs. Stent implantations were performed after pretreatment with aspirin and clopidogrel with unfractionated heparin anticoagulation. Nineteen pigs (groups AST-DES, n=12; and AST-Bare, n=7) died mean 6.3 ± 2.9 h after stent implantation from AST.The remaining 122 control (C) pigs (groups C-DES,n=76,and C-Bare,n=46) survived the 1-month follow-up. Non-significantly elevated levels of post-stent F1+2 and TAT were measured in AST groups. Post-stenting MPV was increased significantly in the groups ASTDES and AST-Bare as compared with the groups C-DES and C-Bare (11.73 ± 1.12 and 11.6 ± 0.68 vs. 8.85 ± 0.78 and 9.04 ± 0.81 fL; p<0.001), similarly toTF-ag (189.1± 87.5 and 127 ± 34.9 vs. 42.5 ± 24.6 and 35.3 ± 37.6 pg/ml; p<0.001, respectively),TF-act (3.23 ± 0.95 and 2.73 ± 1.68 vs. 1.43 ± 1.12 and 1.61 ± 1.31 pM; p<0.01, respectively) and PAI-1 (99.1 ± 15.8 and 99 ± 14.7 vs.53.4 ± 40.2 and 46.9 ± 42.4 ng/ml;p<0.01,respectively).Multivariate analysis revealed elevated post-stenting plasma levels of TF-ag (p=0.016) and MPV (p=0.001) as independent risk factors for developing AST within the first 24 h in a porcine coronary stent model.

Keywords

Platelets - stents - thrombosis - coronary circulation - tissue factor

Full Text

References

References
1 Regar E, Lemos PA, Saia F. et al. Drug eluting stents: are human and animal studies comparable?. Heart 2003; 89: 133-8.
2 Alfonso F, Suarez A, Angiolillo DJ. et al. Findings of intravascular ultrasound during acute stent thrombosis. Heart 2004; 90: 1455-9.
3 Chieffo A, Bonizzoni E, Orlic D. et al. Intraprocedural Stent Thrombosis During Implantation of Sirolimus-Eluting Stents. Circulation 2004; 109: 2732-6.
4 Scheller B, Hennen B, Pohl A. et al. Acute and subacute stent occlusion; risk-reduction by ionic contrast media. Eur HeartJ 2001; 05: 385-91.
5 Gupta V, Aravamuthan BR, Baskerville S. et al. Reduction of subacute stent thrombosis (SAT) using heparin-coated stents in a large-scale, real world registry. J Invasive Cardiol 2004; 16: 304-10.
6 Colombo A, Drzewiecki J, Banning A. et al. for the TAXUS II Study Group Randomized study to assess the effectiveness of slowand moderate-release polymer-based Paclitaxel-eluting stents for coronary artery lesions. Circulation 2003; 108: 788-94.
7 Honda Y, Fitzgerald PJ. Stent thrombosis An issue revisited in a changing world. Circulation 2003; 108: 2-5.
8 Iakovou I, Schmidt T, Bonizzoni E. et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. J Am Med Assoc 2005; 293: 2126-30.
9 Jeremias A, Sylvia B, Bridges J. et al. Stent thrombosis after successful sirolimus-eluting stent implantation. Circulation 2004; 109: 1930-2.
10 Bavry AA, Kumbhani DJ, Helton TJ, Bhatt DL. et al. What is the risk of stent thrombosis associated with the use of paclitaxel-eluting stents for percutaneous coronary intervention?:A meta-analysis. J Am Coll Cardiol 2005; 45: 941-6.
11 Biondi-Zoccai GG, Sangiorgi GM, Chieffo A. RECIPE (Real-world Eluting-stent Comparative Italian retrosPective Evaluation) Investigators Validation of predictors of intraprocedural stent thrombosis in the drug-eluting stent era. Am J Cardiol 2005; 95: 1466-8.
12 Tolleson TR, Newby LK, Harrington RA. et al. SYMPHONY and the 2nd SYMPHONY Investigators Frequency of stent thrombosis after acute coronary syndromes (from the SYMPHONY and 2nd SYMPHONY trials). Am J Cardiol 2003; 92: 330-3.
13 Virmani R, Kolodgie FD, Farb A. et al. Drug eluting stents: are human and animal studies comparable?. Heart 2003; 89: 133-8.
14 Virmani R, Farb A, Guagliumi G. et al. Drug-eluting stents: caution and concerns for long-term outcome. Cor Art Dis 2004; 15: 313-8.
15 Schwartz RS, Huber KC, Murphy JG. et al. Restenosis and the proportional neointimal response to coronary artery injury: results in a porcine model. J Am Coll Cardiol 1992; 19: 267-74.
16 Schwartz RS, Edelman ER. for the Consensus Committee Drug-eluting stents in preclinical studies Recommended evaluation from a consensus group. Circulation 2002; 106: 1867-73.
17 Schwartz RS, Chronos NA, Virmani R. Preclinical restenosis models and drug-eluting stents still important, still much to learn. J Am Coll Cardiol 2004; 44: 1373-85.
18 Wenaweser P, Rey C, Eberli FR. et al. Stent thrombosis following bare metal stent implantation: success of emergency percutaneous coronary intervention and predictors of adverse outcome. Eur Heart J 2005; 26: 1180-7.
19 Saadi BS, Holzknecht RA, Patte C. et al. Complement-mediated regulation of tissue factor activity in endothelium. J Exp Med 1995; 182: 1807-14.
20 Leng HM, Brouwers E, Knockaert I. et al. Immunoassays for the quantitation of porcine PAI-1 antigen and activity in biological fluid samples. Thromb Haemost 2000; 84: 1082-6.
21 Gils A, Declerck PJ. The structural basis for the pathophysiological relevance of PAI-1 in cardiovascular diseases and the development of potential PAI-1 inhibitors. Thromb Haemost 2004; 91: 425-37.
22 Scharf RE, Tomer A, Marzec UM. et al. Activation of platelets in blood perfusing angioplasty-damaged coronary arteries Flow cytometric detection. Arterioscler Thromb 1992; 12: 1475-8.
23 Neumann FJ, Ott I, Gawaz M. et al. Neutrophil and platelet activation at balloon-injured coronary artery plaque in patients undergoing angioplasty. J Am Coll Cardiol 1996; 27: 819-24.
24 Gawaz M, Neumann FJ, Ott I. et al. Platelet activation and coronary stent implantation Effect of antithrombotic therapy. Circulation 1996; 94: 279-85.
25 Serruys PW, Strauss BH, van Beusekom HM. et al. Stenting of coronary arteries: has a modern Pandora’s box been opened?. J Am Coll Cardiol 1991; 17: 143B-54B.
26 Chia S, Megson IL, Ludlam CA. et al. Preserved endothelial vasomotion and fibrinolytic function in patients with acute stent thrombosis or in-stent restenosis. Thromb Res 2003; 111: 343-9.
27 Spronk HMH, van der Voort D, ten Cate H. Blood coagulation and the risk of atherothrombosis: a complex relationship. Thromb J 2004; 02: 12.
28 Palmerini T, Nedelman MA, Scudder LE. et al. Effects of abciximab on the acute pathology of blood vessels after arterial stenting in nonhuman primates. J Am Coll Cardiol 2002; 40: 360-6.
29 Furman MI, Kereiakes DJ, Krueger LA. et al. Leukocyte-platelet aggregation, platelet surface P-selectin and platelet surface glycoprotein IIIa after percutaneous coronary intervention: effects of dalteparin or unfractionated heparin in combination with abciximab. Am HeartJ 2001; 142: 790-821.
30 Lindmark E, Tenno T, Siegbahn A. Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression. Arterioscler Thromb Vasc Biol 2000; 20: 2322-8.
31 Steiner S, Seidinger D, Huber K. et al. Effect of glycoprotein IIb/IIIa antagonist abciximab on monocyteplatelet aggregates and tissue factor expression. Arterioscler Thromb Vasc Biol 2003; 23: 1697-702.
32 Sims PJ, Faioni EM, Wiedmer T. et al. Complement proteins C5b-9 cause release of membrane vesicles from the platelet surface that are enriched in the membrane receptor for coagulation factor Va and express prothombinase activity. J Biol Chemistry 1988; 263: 18205-12.
33 Stampfuss JJ, Censarek P, Fischer JW. et al. Rapid release of active tissue factor from human arterial smooth muscle cells under flow conditions. Arterioscler Thromb Vasc Biol 2006; 26: 34-7.
34 Mackman N. Role of tissue factor in hemostasis, thrombosis, and vascular development. Arterioscler Thromb Vasc Biol 2004; 24: 1015-22.
35 Fuster V, Moreno PR, Fayad ZA. et al. Atherothrombosis and high-risk plaque. J Am Coll Cardiol 2005; 46: 937-54.
36 Huber K. Plasminogen activator inhibitor type-1 (part two): role for failure of thrombolytic therapy PAI-1 resistance as a potential benefit for new fibrinolytic agents. J Thromb Thrombolysis 2001; 11: 195-202.
37 Jeong MH, Owen WG, Staab ME. et al. Porcine model of stent thrombosis: platelets are the primary component of acute stent closure. Cathet Cardiovasc Diagn 1996; 38: 38-43.
38 Rukshin V, Azarbal B, Finkelstein A. et al. Effects of GP IIb/IIIa receptor inhibitor tirofiban (Aggrastat) in ex vivo canine arteriovenous shunt model of stent thrombosis. J Cardiovasc Pharmacol TM 2003; 41: 615-24.
39 Cutlip DE. Stent thrombosis: historical perspectives and current trends. J Thromb Thrombolysis 2000; 10: 89-101.
40 Gyöngyösi M, Domanovits H, Benzer W. et al. ReoPro-BRIDGING Study Group Use of abciximab prior to primary angioplasty in STEMI results in early recanalization of the infarct-related artery and improved myocardial tissue reperfusion - results of the Austrian multi-centre randomized ReoPro-BRIDGING Study. Eur HeartJ 2004; 25: 2125-33.
41 Munster AM, Olsen AK, Bladbjerg EM. Usefulness of human coagulation and fibrinolysis assays in domestic pigs. Comp Med 2002; 52: 39-43.