Antithrombotic effects of recombinant human soluble thrombomodulin (rhs-TM) on arteriovenous shunt thrombosis in rats.
We examined the antithrombotic effect of recombinant human soluble thrombomodulin (rhs-TM) using an arteriovenous shunt thrombosis model and its influence on hemostasis in rats. Intravenous administration of rhs-TM (0.5-4 mg/kg) significantly inhibited thrombus formation and prolonged ex vivo activated partial thromboplastin time (APTT) in a dose-dependent manner. Thrombus formation was inhibited to the same extent in animals treated with heparin (25-200 U/kg) and in those treated with rhs-TM (0.5-4 mg/kg), but heparin had a much stronger effect on prolonging APTT. In the hemorrhagic study using the rat template bleeding time method, rhs-TM exhibited the prolongation of the bleeding time only at the highest effective dose (rhs-TM; 4 mg/kg) of the thrombosis experiments. Thus, rhs-TM exhibits the inhibitory effect on thrombus formation with less APTT prolongation in comparison with heparin and without significant pertubation of hemostasis.
Aoki
Y
Y
Institute for Life Science Research, Asahi Chemical Industry, Shizuoka, Japan.
Takei
R
R
Mohri
M
M
Gonda
Y
Y
Gomi
K
K
Sugihara
T
T
Kiyota
T
T
Yamamoto
S
S
Ishida
T
T
Maruyama
I
I
D000818:Animals; D001166:Arteriovenous Shunt, Surgical / Q000009:adverse effects*; D001760:Bleeding Time; D001777:Blood Coagulation / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006487:Hemostasis / Q000187:drug effects / Q000502:physiology; D006493:Heparin / Q000494:pharmacology; D010314:Partial Thromboplastin Time; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D018180:Thrombomodulin / Q000502:physiology*; D013927:Thrombosis / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology
D005343:Fibrinolytic Agents; D011994:Recombinant Proteins; D018180:Thrombomodulin; D006493:Heparin