In vivo evaluation of DX-9065a, a synthetic factor Xa inhibitor, in experimental vein graft.
An in vivo effect of a novel synthetic Xa inhibitor, DX-9065a, was evaluated in a highly thrombogenic venous graft model. A woven Tetron tube graft was interposed in the inferior vena cava of rabbits. All the grafts were completely occluded within 5 hours after a bolus injection of heparin (50 U/kg) given just prior to the grafting. The following agents were continuously given to the respective group of rabbits for 2 h after the bolus injection of heparin; heparin (50 U/kg/h, UFH-group), DX-9065a (0.05 mg/kg/h, DX-group) and argatroban (32 microG/kg/h, MD-group). During a 5-h observation period, the anti-Xa activity in circulating blood between the UFH- and DX-group and the anti-thrombin activity between the UFH- and MD-group were not significantly different. The graft patency in the DX-group (4/4) and MD-group (4/4) was significantly better than that in the UFH-group (3/10). Ultrastructural analysis of the luminal surface of the harvested graft by scanning electron microscopy revealed the reduced formation of fibrin networks entrapping erythrocytes in the DX- and MD-group in comparison with the patent UFH-group. In conclusion, a novel synthetic Xa inhibitor DX-9065a exerts a potent in vivo antithrombotic effect, which was comparable with argatroban, a synthetic thrombin inhibitor.
Kim
D I
DI
Department of Surgery, Samsung Medical Center, Seoul, Korea.
Kambayashi
J
J
Shibuya
T
T
Sakon
M
M
Kawasaki
T
T
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D000991:Antithrombins / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives; D001807:Blood Vessel Prosthesis; D004195:Disease Models, Animal; D065427:Factor Xa Inhibitors; D006083:Graft Occlusion, Vascular / Q000473:pathology; D006493:Heparin / Q000494:pharmacology; D008297:Male; D008855:Microscopy, Electron, Scanning; D009281:Naphthalenes / Q000494:pharmacology*; D010875:Pipecolic Acids / Q000494:pharmacology; D011422:Propionates / Q000494:pharmacology*; D011817:Rabbits; D013449:Sulfonamides; D013927:Thrombosis / Q000188:drug therapy* / Q000473:pathology
C086910:(2S)-2-(4-(((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy)phenyl)-3-(7-amidino-2-naphtyl)propanoic acid; D000925:Anticoagulants; D000991:Antithrombins; D065427:Factor Xa Inhibitors; D009281:Naphthalenes; D010875:Pipecolic Acids; D011422:Propionates; D013449:Sulfonamides; D006493:Heparin; D001120:Arginine; C031942:argatroban