Hamano S, Komatsu H, Ikeda S, Takahashi K, Oguma Y, Sakuragawa N
Central Research Laboratories, Kissei Pharmaceutical Co. Ltd., Matsumoto, Japan.
Thromb Res. 1989 Aug 15;55(4):439-49. doi: 10.1016/0049-3848(89)90052-2.
The effect of FR-860, one of low molecular weight heparins, was investigated on the hemodialysis model in dogs for comparison with that of conventional unfractionated heparin (UF-heparin). In a bolus injection model, FR-860 at 12.5-100 U/kg prolonged the dialysis time (the time until the arterial circuit pressure reaching 500 mmHg) in a dose-dependent manner and UF-heparin at 50 U/kg also prolonged it. Additionally, FR-860 (12.5-50 U/kg/hr) and UF-heparin (25 and 50 U/kg/hr) continuously inhibited the rise of the arterial circuit pressure in an infusion model. In both models, the efficacy of FR-860 was more potent than that of UF-heparin. FR-860 and UF-heparin decreased the amount of blood loss remaining in the dialyzer in the infusion model. During hemodialysis, both FR-860 and UF-heparin showed activated plasma anti-F.Xa activity, prolongation of aPTT and such of thrombin time in a dose-dependent manner in those models. However, FR-860 was higher in anti-F.Xa activity and weaker in prolongation of aPTT and thrombin time than UF-heparin. These results suggest that FR-860 is more beneficial in in efficacy and higher in safety against the bleeding risk than UF-heparin hemodialysis.
研究了低分子量肝素之一FR - 860对犬血液透析模型的作用,并与传统的普通肝素(UF - 肝素)进行比较。在推注模型中,12.5 - 100 U/kg的FR - 860以剂量依赖的方式延长了透析时间(直至动脉回路压力达到500 mmHg的时间),50 U/kg的UF - 肝素也延长了透析时间。此外,在输注模型中,FR - 860(12.5 - 50 U/kg/小时)和UF - 肝素(25和50 U/kg/小时)持续抑制动脉回路压力的升高。在两种模型中,FR - 860的疗效均强于UF - 肝素。在输注模型中,FR - 860和UF - 肝素均减少了透析器中残留的失血量。在血液透析过程中,在这些模型中,FR - 860和UF - 肝素均呈剂量依赖性地表现出活化的血浆抗F.Xa活性、aPTT延长以及凝血酶时间延长。然而,FR - 860的抗F.Xa活性高于UF - 肝素,而aPTT和凝血酶时间的延长则弱于UF - 肝素。这些结果表明,与UF - 肝素血液透析相比,FR - 860在疗效上更有益,且在出血风险方面安全性更高。