To investigate the concentration- and shear-dependent effects of ethanol on platelet adhesion, activation, and aggregation under pathologically high shear stress mimicking arterial stenosis, and to determine whether its primary target is platelet function or the coagulation cascade. This study aims to resolve the paradoxical relationship between alcohol consumption and cardiovascular risk. Using a validated microfluidic chip platform, we established in vitro models simulating normal vasculature (venous shear: 300 s⁻¹; arterial shear: 1500 s⁻¹) and 80% stenotic vessels (pathological shear: 8200 s⁻¹). Whole blood incubated with ethanol (0.125%-1%) was perfused through microchannels, and platelet adhesion/aggregation was quantified via real-time fluorescence microscopy. Platelet activation under pathological shear was assessed by P-selectin (CD62P) expression using flow cytometry. Comprehensive coagulation function was evaluated through plasma recalcification tests, coagulation profiles (PT/APTT/TT), and thromboelastography (TEG). Ethanol inhibited platelet adhesion and aggregation in a concentration-dependent manner across all shear conditions. Notably, this inhibition exhibited significant shear-dependent enhancement, with maximal efficacy observed at pathological high shear (8200 s⁻¹; p < 0.0001 vs. lower shear rates). Ethanol suppressed shear-induced platelet activation, evidenced by reduced P-selectin expression. Crucially, at all tested concentrations, ethanol did not alter plasma recalcification kinetics, PT/APTT/TT parameters, or TEG metrics (R-value, MA-value, CI-value), confirming its selective targeting of platelets without affecting coagulation cascades. Ethanol exerts concentration- and shear-dependent inhibitory effects on platelet adhesion, activation, and aggregation, with peak efficacy under pathological high shear simulating arterial stenosis. This study, for the first time in a clinically relevant microfluidic model, demonstrates that ethanol specifically targets platelet function while sparing coagulation pathways. These findings provide a mechanistic basis for ethanol’s paradoxical cardiovascular effects—potentially attenuating thrombotic risk in stenotic regions while increasing bleeding propensity.
Liu et al. (Fri,) studied this question.