Agents that elevate cGMP inhibit thrombus formation at high shear. (A) Heparinized human blood was incubated with either vehicle DMSO (i; 0.1%), the phosphodiesterase (PDE) 5 inhibitor sildenafil (1 [ii] or 10 [iii] μM), the NO donor glyco–SNAP-1 (iv; 10 μM) or combination of sildenafil (1 μM) and glyco–SNAP-1 (10 μM) (v) for 5 minutes at room temperature prior to being flowed through 2 × 0.2-mm microslides coated with collagen (300 μg/mL) at 800 s^-1 for 5 minutes. Excess blood was removed from microslides with modified Ca²⁺-free Tyrode buffer flowed at 800 s^-1 for 3 minutes. Thrombi were visualized by light microscope (original magnifications, × 630). Images are representative of 3 experiments. (B) A representative trace for carotid blood flow and mean carotid blood flow (mL/min) from the Folts rabbit model of thrombosis illustrating CFR scores before and after sildenafil (0.01 and 0.03 mg/kg intravenously) administration. CFR scores correspond to the following: 0 indicates complete reduction of flow without spontaneous reversal; 1, reduction of flow with spontaneous reversal; 2, change in rate of flow reduction with spontaneous reversal; and 3, cessation of CFRs.