PAI-1 Inhibition in experimental venous thrombosis

Background A novel PAI-1 inhibitor, MDI-2268, has been recently developed. The aim of the study was to evaluate the antithrombotic effects and safety of the MDI-2268 in acute venous thrombosis (VT) in vivo. Methods C57BL/6 mice, 10–12 weeks old, weighing 20–25g, were used in electrolytic model of VT (EIM). MDI-2268 1.5 mg/kg (Group 1), MDI-2268 3 mg/kg (Group 2), enoxaparin 7.3 mg/kg (Group 3), and MDI-2268 1.5 mg/kg plus enoxaparin 1.8 mg/kg (Group 4) were compared to the controls (sham surgery). Animals were sacrificed on Day 2. Thrombus weight and tail bleeding time were measured. Results TW was 6.9 ± 3.3 ( p > .05), 5.5 ± 1.6 ( p = .016), 3.8 ± 1.3 ( p = .032), and 4.8 ± 2.4 mg ( p = .016) for groups 1, 2, 3, and 4, respectively, compared to the controls. Bleeding time was not significantly affected by the MDI-2268. Conclusions MDI-2268 is a novel pro-fibrinolytic agent that demonstrates strong antithrombotic properties without prolongation of bleeding time in this experimental model.