EXPERIMENTAL STUDIES ON THE INTERACTION OF LW10082 (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 mu m) 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 form ation 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 ora lly for 3 days at a dose of 2 x 10 mg/kg(-1). A 5 mg/kg(-1) dose of LW 10082 given together with Molsidomin produced a strong additive effec t. The combination of LW 10082 and Daltroban also had a significant ad ditive effect.. There was a slight but not significant additive effect between LW 10082 and Ticlopidine. In conclusion, LW 10082 and some ot her antithrombotic agents show additive effects in the prevention of l aser-induced thrombus formation in the rat microcirculation. The clini cal use of such combinations seems possible in patients at high risk o f thrombotic vascular occlusion.