REDUCED ACUTE THROMBUS FORMATION RESULTS IN DECREASED NEOINTIMAL PROLIFERATION AFTER CORONARY ANGIOPLASTY

Objectives. We tested the hypothesis that reduced acute platelet depos ition after angioplasty results in reduced late neointimal proliferati on. Background. Platelet-mediated mechanisms contribute to smooth musc le cell proliferation and migration. Methods. Indium-111-labeled plate lets were injected 16 h before coronary stent angioplasty in 10 Gottin ger minipigs: group 1 (n = 5) = heparin (100 U/kg bolus) before angiop lasty; group 2 (n = 5) = recombinant hirudin (CGP 39393, 1.0 mg/kg bod y weight bolus intravenously), followed by subcutaneous doses of 6 to 10 mg/kg every 8 h. Furthermore, stent angioplasty was performed in co ronary arteries of 16 minipigs: group 3 (n = 5, nine stents) = 100 U/k g heparin only; group 4 (n = 5, 10 stents) = 1-mg/kg bolus hirudin bef ore and 45 min after angioplasty; group 5 (n = 6, 11 stents) = hirudin (1-mg/kg intravenous bolus) before and 45 min after angioplasty, foll owed by 6 to 10 mg/kg subcutaneously every 8 h. Results. In segments w ith 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 signifi cantly less than that in group 1 (mean 375, range 72 to 787 x 10(6)). Morphometric analysis after 4 weeks showed no difference between group s in degree of vessel wall injury. Mean (+/-SD) neointimal thickness w as 0.70 +/- 0.06 mm in group 3 and was significantly reduced in both g roup 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 bolu s alone as well as continued subcutaneous administration for 14 days s ubstantially reduced neointimal proliferation compared with heparin 4 weeks after coronary stent angioplasty in minipigs.