Antithrombotic Efficacy of a Recombinant Nematode Anticoagulant Peptide (rNAP5) in Canine Models of Thrombosis after Single Subcutaneous Administration

摘要: We describe the antithrombotic effects of recombinant nematode anticoagulant peptide (rNAP5), a selective and direct factor Xa inhibitor, after single s.c. administration in canine models arterial venous thrombosis. The systemic rNAP5 were evaluated initially conscious dogs dosing (0.03, 0.1 0.3 mg/kg) that resulted dose-dependent increase activated clotting time partial thromboplastin time. anesthetized where saline or mg/kg s.c.) was administered 1 hr before left circumflex coronary artery subjected to electrolytic injury. In group (n = 10), occluded 79 +/- 9 min, 5 10 animals progressed sudden death due ventricular fibrillation. significantly prolonged occlusion 0.03 (163 62 min) (327 62) treatment groups 6). 5), all injured vessels remained patent for 8 hr. There reduction thrombus mass rNAP5-treated as compared with controls, well lower mortality rate. rNAP5, doses mg/kg, did not alter bleeding time, whereas produced 5-fold increase. separate study, we efficacy (0.1 prevention carotid jugular vein response endothelial injury, 6) 142 16 100 11 respectively, which maintained vessel patency (6/6) (5/6) decreased weights. results demonstrate has thrombosis administration.