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  • Title: Reduced acute thrombus formation results in decreased neointimal proliferation after coronary angioplasty.
    Author: Unterberg C, Sandrock D, Nebendahl K, Buchwald AB.
    Journal: J Am Coll Cardiol; 1995 Dec; 26(7):1747-54. PubMed ID: 7594113.
    Abstract:
    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 Göttinger 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.
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