Experimental Studies on the Interaction of LW 10082 (Aprosulphate) with Other Antithrombotic Agents in Laser-Induced Thrombosis

Abstract.

The aim of this study was to investigate the possible interactions of LW 10082 with several other antithrombotic agents. The antithrombotic effects of all agents were studied in a thrombosis model in which rat mesenteric venules (diameter 20–30 μm) were injured by well-defined argon laser lesions. The number of laser injuries which were needed to induce a thrombus that intermittently occluded the vessel was used to quantify the results. LW 10082 was injected s.c. 2 h before testing. The minimal effective dose which significantly inhibited thrombus formation was 5 mg/kg⁻¹. The minimal effective dose of Daltroban (orally 2 h before testing) was 10 mg/kg⁻¹. At 30 min after i.v. injection of 0.1 mg/kg⁻¹ Molsidomin, a significant antithrombotic activity was present. Ticlopidine inhibited thrombus formation if administered orally for 3 days at a dose of 2×10 mg/kg⁻¹. A 5 mg/kg⁻¹ dose of LW 10082 given together with Molsidomin produced a strong additive effect. The combination of LW 10082 and Daltroban also had a significant additive effect. There was a slight but not significant additive effect between LW 10082 and Ticlopidine. In conclusion, LW 10082 and some other antithrombotic agents show additive effects in the prevention of laser-induced thrombus formation in the rat microcirculation. The clinical use of such combinations seems possible in patients at high risk of thrombotic vascular occlusion.