S14161 inhibited platelet adhesion on collagen-coated surfaces under flow ex vivo and thrombus formation in vivo, but not hemostasis.
(A) Human whole blood was labeled with Calcein-AM, treated with (lower channels) or without (upper channels) S14161 (10 µM), and perfused over collagen-coated surface at a shear rate of 40 dyn/cm2 (1000 s−1). Platelet adhesion and aggregates were photographed. Data plotted are means ± standard errors of fluorescence intensity of three individual experiments (**P<0.01, ***P<0.001). Arrow indicates the flow direction. (B) S14161 (2 mg/kg) (n = 9) or vehicle (n = 8) was administered intraperitoneally to mice and time to occlusion of the carotid artery after the application of 7.5% FeCl3 for two minutes was measured using Visual Sonics View 2100. Time to loss of blood flow was recorded. (C) S14161 (2 mg/kg) (n = 12) or vehicle (n = 10) was administered intraperitoneally to mice. The bleeding end was immersed in saline at 37°C, and the time to bleeding cessation was recorded. *P<0.05 vs. vehicle control. N.S. means no significance.
