Local delivery of r-hirudin by a double-balloon perfusion catheter prevents mural thrombosis and minimizes platelet deposition after angioplasty.

摘要: BACKGROUND The major morbidity of percutaneous transluminal coronary angioplasty is acute thrombosis and restenosis the dilated lesion. Platelet-thrombus deposition occurs within minutes after injury, primarily mediated by thrombin, causes occlusion, contributes to late restenosis. Experimentally, specific thrombin inhibitors have prevented mural thrombosis. However, local therapy may be more effective than systemic treatment. We tested hypothesis that high concentrations an antithrombin drug at site arterial injury following balloon inhibit platelet thrombus formation equally or better conventional treatment lower anticoagulant levels. METHODS AND RESULTS Balloon carotid arteries 29 pigs was performed using intravenous with heparin (100 U/kg, groups I II), suboptimal r-hirudin (0.3 mg/kg, group III), higher-dose (0.7 IV), which lowest dose completely inhibited in pig. Immediately first carotid, additional placebo (group I) (groups II, III, IV; 0.3 mg/kg 1 mL) administered distal perfusion through a new double-balloon catheter. After hour delivery, contralateral performed. Reflow for permitted both carotids compare short-term effect plus on quantitative 111In-labeled macroscopic deeply injured segments. Local delivery compared resulted no change (x 10(6)/cm2, mean +/- SEM) controls I, 91.0 23.5 versus 80.8 19.4), but significant reduction II (15 2.5 71.3 14.5; P < .02) III (11.4 80.5 11.4; .01) borderline IV (7.4 1.8 14.1 7.4; = .05), respectively. incidence 86% 75% 16% 70% 14% 71% 0% IV, respectively. CONCLUSIONS inhibitor significantly reduces doses hirudin requires smaller amount recombinant drug.