Popis: |
Different supersulphated low molecular weight heparins (SSLMWH, Lab. Code: SSH 11, SSH 13, SSH 14), isolated after controlled depolymerisation and contemporary sulphatation of pig mucosal unfractionated heparin (Italian Patent 22504 A189), were tested for their in vitro and in vivo t-PA releasing activity. The different SSH preparations developed profibrinolytic activity on the basis of tissue-type plasminogen activator (t-PA) release during perfusion of isolated pig ear and after i.v.-application in rats. The acute t-PA release induced by SSH 11, 13 and 14 was in a higher range in the isolated perfused pig ear model than that induced by unfractionated heparin at a concentration of 50 μg/ml perfusion solution. The highest acute increase of t-PA was caused by SSH 14 with 200%. SSH 14 was dose-dependently tested for acute t-PA release in rats after intravenous administration of 1.0, 2.5, 5.0 and 10.0 mg SSH/kg body weight. The maximum net increase of t-PA release was reached 1 to 5 min after i.v. application of SSH 14. After the administration of 5 or 10 mg/kg, resp., SSH 14 produced an increase in maximum t-PA release between 7 and 8 I.U./ml plasma. The t-PA releasing effect of SSLMWH might contribute to the antithrombotic effect of SSH 14. |