Author + information
- Received March 16, 1995
- Revision received July 7, 1995
- Accepted July 12, 1995
- Published online December 1, 1995.
- Christina Unterberg, MD*,
- Dirk Sandrock, MD,
- Klaus Nebendahl, MD and
- Arnd B. Buchwald, MD
- ↵*Address for correspondence: Dr. Christina Unterberg, Department of Cardiology, University Clinic, Robert-Koch-Strasse 40, D-37075 Göttingen, 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 Göttinger minipigs: group I(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 × 106) was significantly less than that in group 1 (mean 375, range 72 to 787 × 106). 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 work contains parts of the Habilitationsschrift of Christina Unterberg. The hirudin (CGP 39393) used in this study was provided by Ciba Geigy Pharmaceuticals, Basel, Switzerland and the stents by Medtronic GmbH, Düsseldorf, Germany.
- Received March 16, 1995.
- Revision received July 7, 1995.
- Accepted July 12, 1995.
- American College of Cardiology