Comparative study on the in vitro and in vivo activities of heparinoids derivative investigated on the animal model

In this study we compared the antithrombotic and anticoagulant properties o f 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 e xperimental thrombosis model in which rat mesenteric venules with a diamete r of 20-30 mu m were injured by well-defined argon laser lesions. Furthermo re, the in vivo and in vitro anticoagulant activities [activated partial th romboplastin time (aPTT), Heptest] of these agents have been studied. Throm bus formation was significantly inhibited after s.c. injection of Na-PPS an d Ca-PPS in doses >10 mg/kg. The duration of the antithrombotic effect last ed 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 d oses >20 mg/kg significantly inhibited thrombus formation. Na-PPS and Ca-PP S markedly prolonged clotting time in aPTT and Heptest in concentrations ra nging from 0.01 to 0.2 mg/ml rat PTT. Two h after s.c. administration of th ese agents in a dose of 10 mg/kg, the aPTT increased threefold and the Hept est 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. Intrav enous 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 bet ween 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 o f 20 U/kg UFH significantly inhibited thrombus formation. The smallest anti thrombotic effect was after i.v. injection of UFH.