Figure 7. Inhibition of platelet P2Y₁₂ receptor abrogates hemolysis-induced pulmonary thrombosis in mice.

(A) WT mice were administered 10 mg/kg prasugrel by oral gavage and then IV challenged with 150 μL dH₂O. Pulmonary circulation was imaged using quantitative fluorescence intravital lung microscopy (qFILM). qFILM images of the same field of view (FOV) at 6 different time points are shown. t = 0 seconds (s) corresponds to time point before and t > 0 s correspond to time points immediately following IV dH₂O administration. Pulmonary thrombosis was absent at t = 0 s. dH₂O failed to evoke pulmonary thrombosis in mouse pretreated with prasugrel. Platelets (green) and pulmonary microcirculation (purple). Asterisks denote alveoli. White arrows mark the direction of blood flow within the feeding arterioles. The diameter of the arteriole shown is 30 μm. Scale bar: 50 μm. Also refer to Supplemental Video 11. (B) Pulmonary thrombi area plotted as a function of time for the FOV shown in A. Red arrow indicates pulmonary thrombi maximum area. (C and D) Pulmonary thrombi max area and AUC in mice with (n = 6 mice) or without (n = 7 mice) pretreatment with prasugrel before IV dH₂O. Pulmonary thrombi max area and AUC were estimated as described in Methods. Pulmonary thrombi max area and AUC were compared using Wilcoxon-Mann-Whitney test. Data are shown as mean ± SEM. *P < 0.05, **P < 0.01 when comparing with and without prasugrel pretreatment.