Interaction between the sulfated lactobionic acid (LW 10082) and other antithrombotic agents in animal thrombosis model.
We investigated the comparative antithrombotic properties of LW 10082, acetylasalicylic acid (Aspisol), low molecular weight heparin (LMWH, CY 216) and sodium heparin using laser-induced thrombosis model. The animal model which has been used is well suited to observe platelet reactions to damaged endothelial cells and also to evaluate the effect of drugs on the formation of platelet thrombi. The rat mesenteric venules with a diameter of 20-30 microns were injured by well defined argon laser lesion. The number of laser injuries which were needed to induce a thrombus intermittently occluded the vessel was counted to quantitate the results. LW 10082 was injected sc 2 h prior to testing. The minimal effective dose of LW 10082 which significantly inhibited thrombus formation was 5 mg/kg. The antithrombotic effect of Aspisol has been investigated after its oral application at doses of 1.5 and 10 mg/kg 2 h before studying the antithrombotic effect. The minimal effective dose for Aspisol was 10 mg/kg. The LMWH has been injected into the rat tail vein in doses of 1, 0.2 and 0.1 mg/kg 30 min before testing. 0.1 mg/kg did not have any antithrombotic effect. The minimal effective dose of the sodium heparin which significantly inhibited thrombus formation was 20 U/kg measured 30 min after its iv injection. The combination of minimal effective dose of LW 10082 and LMWH had a significant additive effect. There was a slight but not significant additive effect between LW 10082, Aspisol and heparin sodium. Our results suggest that combinations of LW 10082 with LMWH may provide a new approach to more effective prophylaxis and treatment of venous or arterial thrombosis.
Giedrojć
J
J
Department of Haematology, Medical Academy, Białystok, Poland.
Krupiński
K
K
Breddin
H K
HK
Bielawiec
M
M
D000818:Animals; D001241:Aspirin / Q000627:therapeutic use; D004187:Disaccharides / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006493:Heparin / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000627:therapeutic use; D007834:Lasers / Q000009:adverse effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013924:Thrombophlebitis / Q000188:drug therapy*
D004187:Disaccharides; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D006493:Heparin; D001241:Aspirin; C069690:aprosulate