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

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.