title: Reduced acute thrombus formation results in decreased neointimal proliferation after coronary angioplasty.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, University of Göttingen, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Unterberg
authors.forename: D
authors.initials: D
authors.lastname: Sandrock
authors.forename: K
authors.initials: K
authors.lastname: Nebendahl
authors.forename: A B
authors.initials: AB
authors.lastname: Buchwald
mesh_terms: D015906:Angioplasty, Balloon, Coronary / Q000009:adverse effects*; D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use*; D001792:Blood Platelets / Q000473:pathology; D002455:Cell Division; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D005337:Fibrin / Q000378:metabolism; D006493:Heparin / Q000627:therapeutic use; D024764:Hirudin Therapy; D006629:Hirudins / Q000031:analogs & derivatives; D010314:Partial Thromboplastin Time; D011994:Recombinant Proteins / Q000627:therapeutic use; D015607:Stents; D013552:Swine; D013556:Swine, Miniature; D013927:Thrombosis / Q000473:pathology / Q000517:prevention & control*; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D000925:Anticoagulants; D006629:Hirudins; D011994:Recombinant Proteins; D005337:Fibrin; D006493:Heparin; C060225:desirudin