P2Y12 or P2Y1 inhibitors reduce platelet deposition in a microfluidic model of thrombosis while apyrase lacks efficacy under flow conditions.

ABSTRACT: Determination of the patient-specific response to antiplatelet agents facilitates proper dosing for both acute and chronic prophylaxis. "Closed" systems (with or without flow) may fail to predict pharmacological potency in situations where platelets rapidly accumulate under flow conditions at a site of thrombosis ("Open" systems). Using an 8-channel microfluidic flow assay of human whole blood with corn trypsin inhibitor (+/- PPACK) perfused over focal zones of collagen, dose-response curves were measured for pharmacological agents at a wall shear rate of 210 s(-1). The P2Y(1) inhibitor MRS 2179 (IC(50) = 0.233 +/- 0.132 microM) and P2Y(12) inhibitor 2-MeSAMP (IC(50) = 2.558 +/- 0.799 microM) were potent blockers of secondary platelet accumulation under flow, while the P2X(1) inhibitor (NF

SUBMITTER: Maloney SF 

PROVIDER: S-EPMC4441395 | biostudies-literature | 2010 Apr

REPOSITORIES: biostudies-literature