Kim D I, Kambayashi J, Shibuya T, Sakon M, Kawasaki T
Department of Surgery, Samsung Medical Center, Seoul, Korea.
J Atheroscler Thromb. 1996;2(2):110-6. doi: 10.5551/jat1994.2.110.
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.
在高度致血栓形成的静脉移植物模型中评估了新型合成Xa抑制剂DX-9065a的体内效应。将编织的特氟龙管移植物植入兔的下腔静脉。在植入前即刻给予大剂量肝素（50 U/kg）后，所有移植物在5小时内完全闭塞。在给予肝素大剂量注射后，分别对各组兔连续给药2小时；肝素（50 U/kg/h，UFH组）、DX-9065a（0.05 mg/kg/h，DX组）和阿加曲班（32 μg/kg/h，MD组）。在5小时的观察期内，UFH组和DX组之间循环血液中的抗Xa活性以及UFH组和MD组之间的抗凝血酶活性无显著差异。DX组（4/4）和MD组（4/4）的移植物通畅率显著优于UFH组（3/10）。通过扫描电子显微镜对收获的移植物管腔表面进行超微结构分析显示，与通畅的UFH组相比，DX组和MD组中包绕红细胞的纤维蛋白网络形成减少。总之，新型合成Xa抑制剂DX-9065a具有强大的体内抗血栓作用，与合成凝血酶抑制剂阿加曲班相当。
