Reduced acute thrombus formation results in decreased neointimal proliferation after coronary angioplasty

Department of Cardiology, University of Gottingen, Germany.

OBJECTIVES. We tested the hypothesis that reduced acute platelet deposition after angioplasty results in reduced late neointimal proliferation. BACKGROUND. Platelet-mediated mechanisms contribute to smooth muscle cell proliferation and migration. METHODS. Indium-111-labeled platelets were injected 16 h before coronary stent angioplasty in 10 Gottinger minipigs: group 1 (n = 5) = heparin (100-U/kg bolus) before angioplasty; group 2 (n = 5) = recombinant hirudin (CGP 39393, 1.0-mg/kg body weight bolus intravenously), followed by subcutaneous doses of 6 to 10 mg/kg every 8 h. Furthermore, stent angioplasty was performed in coronary arteries of 16 minipigs: group 3 (n = 5, nine stents) = 100 U/kg heparin only; group 4 (n = 5, 10 stents) = 1-mg/kg bolus hirudin before and 45 min after angioplasty; group 5 (n = 6, 11 stents) = hirudin (1-mg/kg intravenous bolus) before and 45 min after angioplasty, followed by 6 to 10 mg/kg subcutaneously every 8 h. RESULTS. In segments with deep arterial injury, the number of platelets/angioplasty segment in group 2 after 72 h (mean 21, range 9.7 to 39.7 x 10(6)) was significantly less than that in group 1 (mean 375, range 72 to 787 x 10(6)). Morphometric analysis after 4 weeks showed no difference between groups in degree of vessel wall injury. Mean (+/- SD) neointimal thickness was 0.70 +/- 0.06 mm in group 3 and was significantly reduced in both group 4 (0.46 +/- 0.11 mm) and group 5 (0.48 +/- 0.21 mm). CONCLUSIONS. The direct thrombin inhibitor hirudin significantly reduces platelet deposition up to 72 h after coronary stent angioplasty. A hirudin bolus alone as well as continued subcutaneous administration for 14 days substantially reduced neointimal proliferation compared with heparin 4 weeks after coronary stent angioplasty in minipigs.

This article has been cited by other articles:

				C. Tamburino, A. La Manna, M. E. Di Salvo, G. Sacchetta, D. Capodanno, R. Mehran, G. Dangas, T. Corcos, and F. Prati First-in-Man 1-Year Clinical Outcomes of the Catania Coronary Stent System With Nanothin Polyzene-F in De Novo Native Coronary Artery Lesions: The ATLANTA (Assessment of The LAtest Non-Thrombogenic Angioplasty stent) Trial J. Am. Coll. Cardiol. Intv., March 1, 2009; 2(3): 197 - 204. [Abstract] [Full Text] [PDF]

				M. N. Babapulle and M. J. Eisenberg Coated Stents for the Prevention of Restenosis: Part I Circulation, November 19, 2002; 106(21): 2734 - 2740. [Full Text] [PDF]

				A. B. Buchwald, A. H. Wagner, C. Webel, and M. Hecker Decoy oligodeoxynucleotide againstactivator protein-1 reducesneointimal proliferation after coronaryangioplasty in hypercholesterolemic minipigs J. Am. Coll. Cardiol., February 20, 2002; 39(4): 732 - 738. [Abstract] [Full Text] [PDF]

				M. Singh, G. S. Reeder, E. M. Ohman, V. Mathew, W. B. Hillegass, R. D. Anderson, D. S. Gallup, K. N. Garratt, and D. R. Holmes Jr Does the presence of thrombus seen on a coronary angiogram affect the outcome after percutaneous coronary angioplasty? An angiographic trials pool data experience J. Am. Coll. Cardiol., September 1, 2001; 38(3): 624 - 630. [Abstract] [Full Text] [PDF]

				Y. Cottin, M. Kollum, R. Chan, B. Bhargava, Y. Vodovotz, and R. Waksman Vascular repair after balloon overstretch injury in porcine model effects of intracoronary radiation J. Am. Coll. Cardiol., October 1, 2000; 36(4): 1389 - 1395. [Abstract] [Full Text] [PDF]

				E. Alt, I. Haehnel, C. Beilharz, K. Prietzel, D. Preter, A. Stemberger, T. Fliedner, W. Erhardt, and A. Schomig Inhibition of Neointima Formation After Experimental Coronary Artery Stenting : A New Biodegradable Stent Coating Releasing Hirudin and the Prostacyclin Analogue Iloprost Circulation, March 28, 2000; 101(12): 1453 - 1458. [Abstract] [Full Text] [PDF]

				J. St. Pierre, L.-Y. Yang, K. Tamirisa, D. Scherrer, P. De Ciechi, P. Eisenberg, E. Tolunay, and D. Abendschein Tissue Factor Pathway Inhibitor Attenuates Procoagulant Activity and Upregulation of Tissue Factor at the Site of Balloon-Induced Arterial Injury in Pigs Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2263 - 2268. [Abstract] [Full Text] [PDF]

				W. H. Matthai Jr., P. B. Kurnik, W. C. Groh, W. J. Untereker, and J. E. Siegel Antithrombin activity during the period of percutaneous coronary revascularization: Relation to heparin use, thrombotic complications and restenosis J. Am. Coll. Cardiol., April 1, 1999; 33(5): 1248 - 1256. [Abstract] [Full Text] [PDF]

				Y. Ueda, M. Kitakaze, M. Imakita, H. Ishibashi-Ueda, T. Minamino, H. Asanuma, T. Ozaki, E. Imamura, T. Kuzuya, and M. Hori Glycoprotein IIb/IIIa Antagonist FK633 Could Not Prevent Neointimal Thickening in Stent Implantation Model of Canine Coronary Artery Arterioscler Thromb Vasc Biol, February 1, 1999; 19(2): 343 - 347. [Abstract] [Full Text] [PDF]

				T.-Ph. Zucker, D. Bonisch, S. Muck, A.-A. Weber, E. Bretschneider, E. Glusa, and K. Schror Thrombin-Induced Mitogenesis in Coronary Artery Smooth Muscle Cells Is Potentiated by Thromboxane A2 and Involves Upregulation of Thromboxane Receptor mRNA Circulation, February 17, 1998; 97(6): 589 - 595. [Abstract] [Full Text] [PDF]

				V. B. Schini-Kerth, S. Bassus, B. Fisslthaler, C. M. Kirchmaier, and R. Busse Aggregating Human Platelets Stimulate the Expression of Thrombin Receptors in Cultured Vascular Smooth Muscle Cells via the Release of Transforming Growth Factor- 1 and Platelet-Derived Growth FactorAB Circulation, December 2, 1997; 96(11): 3888 - 3896. [Abstract] [Full Text]

				M. W. Liu, P. G. Anderson, J. F. Luo, and G. S. Roubin Local Delivery of Ethanol Inhibits Intimal Hyperplasia in Pig Coronary Arteries After Balloon Injury Circulation, October 7, 1997; 96(7): 2295 - 2301. [Abstract] [Full Text]

				L. Oltrona, C. M. Speidel, D. Recchia, S. A. Wickline, P. R. Eisenberg, and D. R. Abendschein Inhibition of Tissue Factor Mediated Coagulation Markedly Attenuates Stenosis After Balloon-Induced Arterial Injury in Minipigs Circulation, July 15, 1997; 96(2): 646 - 652. [Abstract] [Full Text]

				C. Gerdes, V. Faber-Steinfeld, O. Yalkinoglu, and S. Wohlfeil Comparison of the Effects of the Thrombin Inhibitor r-Hirudin in Four Animal Models of Neointima Formation After Arterial Injury Arterioscler Thromb Vasc Biol, October 1, 1996; 16(10): 1306 - 1311. [Abstract] [Full Text]