Antiplatelet Effect of Hirudin in a Rabbit Carotid Artery Eversion Model

ABSTRACT

BACKGROUND AND OBJECTIVES: Thrombin and its interaction with platelets play a pivotal role in arterial thrombus formation. Hirudin, an anticoagulant agent derived from medicinal leeches(Hirudo medicinalis), is a unique and specific thrombin inhibitor with no effect on other serine protease. We investigated the inhibitory effect of hirudin on platelet deposition in a rabbit carotid artery eversion model of acute arterial thrombosis. MATERIALS AND METHODS: The everted arterial segments were perfused with 111 Indium-labeled human platelets only(control, n=8), and a mixed solution of 111 Indium-labeled human platelets and hirudin(30, 45, 60, 90 microgram/ml, n=3, respectively). Platelet deposition was calculated by a gamma-counter and confirmed by scanning electron microscopy. RESULTS: 1) Indium-111 labeling efficiency of platelets was 87.0+/-6.6%, and the aggregation of platelets was not changed after labeling. The number of platelets perfused through each arterial segment was 4.3 +/-0.2x10(8) platelets/ml. 2) The control group showed a platelet deposition rate of 23.9+/-7.0 % and a number of platelet deposition of 9.8+/-2.5x10(8) platelets/cm2 . 3) Platelet deposition of arteries perfused with hirudin(60 microgram/ml) was significantly decreased compared with that of the control group(2.9+/-0.6 vs 9.8+/-2.5x10(8)/cm2 , p<0.05). 4) The number of deposited platelets in hirudin-perfused arteries was dose-dependently decreased(30 microgram/ml6.7+/-1.4x10(8) /cm2 , 45 microgram/ml 4.8+/-1.7x10(8) /cm2 , 60 microgram/ml 2.9+/-1.8x10(8)/cm2, 90 microgram/ml2.9+/-1.4x10(8)/cm2 p<0.05 vs. control, respectively). 5) Scanning electron microscopic examination revealed significantly reduced platelet deposition in hirudin-perfused groups compared with control group. CONCLUSION: Hirudin inhibits effectively platelet deposition and arterial thrombus formation in a rabbit carotid artery eversion model. The antiplatelet effect of hirudin in this model suggests that hirudin may be an useful antithrombotic agent therapeutically useful in the prevention of acute arterial thrombus formation.