Figure 7.

PRT060318 activity in rabbits and pigs. (A) In vitro (spiking experiments) mean thrombotic profiles in presence of vehicle control (V.Ctl.) or PRT060318 (1 and 3μM) in rabbits. (B) Ex vivo thrombotic profiles associated with V. Ctl. or PRT060318 infusion regimen (intravenous infusion regimen was initiated before vascular injury and established as follows: from 0 to 15 minutes, 20.67 mg/kg/h at 12.4 mL/kg/h and then from 15 minutes until the end, 7.33 mg/kg/h at 4.4 mL/kg/h). (C) Occlusion rate in vivo in the rabbit thrombosis model. P = .021 by Gehan–Breslow survival analysis with Bonferroni comparison. (D) In vitro mean thrombotic profiles of whole blood from 4 pigs treated with DMSO (blue curve) or 3μM PRT060318. Intravenous infusion of PRT060318 (8.90 mg/kg/h at 1 mL/kg/h) in pigs inhibited ¹¹¹In-labeled platelet deposition in vivo in the pig thrombosis model (E), abolished ex vivo platelet aggregation induced by CVXN (250 ng/mL) but not ADP (20μM; F), and did not affect the ear bleeding time (G).