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Effect of a Selective Thrombin Inhibitor MCI-9038 on Fibrinolysis In Vitro and In Vivo
| Content Provider | Scilit |
|---|---|
| Author | Tamao, Y. Yamamoto, T. Kikumoto, R. Hara, H. Itoh, J. Hirata, T. Mineo, K. Okamoto, S. |
| Copyright Year | 1986 |
| Description | The effect of a selective thrombin inhibitor, (2R, 4R)-4-methyl-1- $[N^{2}$- [(3-methyl-1,2,3,4-tetrahydro-8-quinolinyl)sulfo-nyl]-L-arginyl]-2-piperidinecarboxylic acid (MCI-9038), on the fibrinolysis induced by t-PA and u-PA was studied in vitro and in vivo. MCI-9038 remarkably reduced the lysis time of the plasma clot generated by the addition of calcium chloride to the plasma at the concentration ranging from 0.01 to 0.3 μM. Heparin also reduced the plasma clot lysis time with a lower effect than MCI-9038. The fibrin crosslinkage in the plasma clot was inhibited by MCI-9038 or heparin. MCI-9038 potently inhibited the factor XIIIa generation from factor XIII by thrombin. The effect on the in vivo thrombolysis was studied on the arterial thrombosis generated by the endothelial cell injury of the rabbit carotid artery by acetic acid. t-PA dissolved the thrombi with the infusion at 0.96 mg/kg over 2 h without a significant activation of a systemic fibrinolysis. u-PA dissolved the thrombi with the infusion at 180,000 and 360,000 IU/kg over 2 h. At a dose of 0.48 mg/kg t-PA or 90,000 IU/kg u-PA, the thrombi were not dissolved, but the combined use of MCI-9038 at 1.2 mg/kg over 2 h effectively dissolved the thrombi. Thus, combination of MCI-9038 with plasminogen activators accelerated thrombolysis of an experimental thrombosis in rabbits. |
| Related Links | http://www.thieme-connect.de/products/ejournals/pdf/10.1055/s-0038-1661597.pdf |
| Ending Page | 034 |
| Page Count | 7 |
| Starting Page | 028 |
| ISSN | 2567689X |
| DOI | 10.1055/s-0038-1661597 |
| Journal | Thrombosis and Haemostasis |
| Issue Number | 01 |
| Volume Number | 56 |
| Language | English |
| Publisher | Georg Thieme Verlag KG |
| Publisher Date | 1986-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Thrombosis and Haemostasis Tissue-type Plasminogen Activator Urokinase-type Plasminogen Activator Thrombin Inhibitor Md-805 Plasma Clot Lysis Experimental Thrombosis |
| Content Type | Text |
| Resource Type | Article |
| Subject | Hematology |
