title: Comparative study on the in vitro and in vivo activities of heparinoids derivative investigated on the animal model.
abstract: In this study we compared the antithrombotic and anticoagulant properties of sodium and calcium derivatives of pentosan polysulfate (Na-PPS, Ca-PPS), unfractionated heparin (UFH), and low-molecular-weight heparin (Fraxiparin). The antithrombotic effects of these agents have been investigated in an experimental thrombosis model in which rat mesenteric venules with a diameter of 20-30 microm were injured by well-defined argon laser lesions. Furthermore, the in vivo and in vitro anticoagulant activities [activated partial thromboplastin time (aPTT), Heptest] of these agents have been studied. Thrombus formation was significantly inhibited after s.c. injection of Na-PPS and Ca-PPS in doses >10 mg/kg. The duration of the antithrombotic effect lasted 8 h for Na-PPS and 12 h for Ca-PPS. After oral administration of Na-PPS, an antithrombotic effect was not observed. Oral application of Ca-PPS in doses >20 mg/kg significantly inhibited thrombus formation. Na-PPS and Ca-PPS markedly prolonged clotting time in aPTT and Heptest in concentrations ranging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of these agents in a dose of 10 mg/kg, the aPTT increased threefold and the Heptest 2.5-fold compared with controls. After oral application of 50 mg/kg Na-PPS and Ca-PPS, no effect on the coagulation test could be measured. Intravenous injection of UFH prolonged the Heptest after 1 min and the aPTT after 30 min. In ex vivo studies of aPTT and Heptest performed in rat plasma between 2 and 24 h after s.c. injection of 0.2 mg/kg Fraxiparin, no inhibition of any coagulation test was measured. The antithrombotic effect of 0.2 mg/kg Fraxiparin after s.c. injection was significant. Intravenous injection of 20 U/kg UFH significantly inhibited thrombus formation. The smallest antithrombotic effect was after i.v. injection of UFH.
authors.affiliation: Department of Haematology, University Medical School, Białstok, Poland.
authors.forename: J
authors.initials: J
authors.lastname: Giedrojć
authors.forename: M
authors.initials: M
authors.lastname: Klimiuk
authors.forename: P
authors.initials: P
authors.lastname: Radziwon
authors.forename: J
authors.initials: J
authors.lastname: Kłoczko
authors.forename: M
authors.initials: M
authors.lastname: Bielawiec
authors.forename: H K
authors.initials: HK
authors.lastname: Breddin
mesh_terms: D000818:Animals; D001779:Blood Coagulation Factors / Q000037:antagonists & inhibitors; D004195:Disease Models, Animal; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006496:Heparinoids / Q000737:chemistry / Q000627:therapeutic use*; D007834:Lasers; D008297:Male; D017762:Nadroparin / Q000627:therapeutic use; D010426:Pentosan Sulfuric Polyester / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000378:metabolism; D020246:Venous Thrombosis / Q000188:drug therapy*
chemical_list: D001779:Blood Coagulation Factors; D005343:Fibrinolytic Agents; D006496:Heparinoids; D017762:Nadroparin; D010426:Pentosan Sulfuric Polyester; D006493:Heparin