A microchip flow-chamber system for quantitative assessment of the platelet thrombus formation process

Publication date: March 2012 Source:Microvascular Research, Volume 83, Issue 2 Author(s): Kazuya Hosokawa , Tomoko Ohnishi , Masashi Fukasawa , Taro Kondo , Hisayo Sameshima , Takehiko Koide , Kenichi A. Tanaka , Ikuro Maruyama As the pathogenesis of arterial thrombosis often includes platelet thrombus formation (PTF), antiplatelet agents are commonly used for the prevention of thromboembolic events. Here, using a novel microchip flow-chamber system we developed to quantitatively analyze the PTF process, we evaluated the pharmacological efficacies of antiplatelet agents under different arterial shear rates. Hirudin-anticoagulated whole blood was perfused over a collagen-coated microchip at shear rates of 1000, 1500, and 2000s−1, and PTF in the absence and presence of various antiplatelet agents was observed microscopically and quantified by measuring flow-pressure changes. The onset of PTF was measured as T10 (time to reach 10kPa), and AUC10 (area under the flow pressure curve for the first 10min) was calculated to quantify the overall stability of the formed thrombus. Aspirin and AR-C66096 (P2Y12-antagonist) at high concentrations (50μM and 1000nM, respectively) prolonged T10 only modestly (AR-C66096>aspirin), but effectively decreased AUC10, resulting in unstable PTF at all examined shear rates. With dual inhibition using both aspirin (25μM) and ARC-66096 (250 nM), AUC10 was drastically reduced. Nearly complete suppression of AUC10 was also observed w...
Source: Microvascular Research - Category: Biochemistry Source Type: research