Flow induced platelet activation in models of blood recirculating devices

Thromboembolic complications still comprise a significant drawback in the use of cardiovascular devices and synthetic biomaterials implants which recirculate blood. The thrombogenicity of cardiovascular devices i primarily due to platelet activation by interaction with foreign surfaces and b non-physiological flow patterns. The latter are induced by the design characteristics of the device. Shear rates and flow patterns (fluid dynamics factors), and concentration of coagulation factors and platelet agonists (biological factors), modulate platelet function and may lead to platelet activation and aggregation. Two complementary experimental techniques were combined in order to examine how the flow-induced stresses that are generated in constrictions elicit platelet activation and aggregation. The constrictions serve as a model for cardiovascular devices such as prosthetic heart valves, vascular grafts, and ventricular assist devices. The measurements were based on identical in vitro flow loops with recirculating stenosis models. One flow loop utilized optically clear scaled up stenosis models and water-glycerin mixture to obtain quantitative flow visualization by Continuous Digital Particle Image Velocimetry (CDPIV). Its scaled replica employed human platelet buffer in which platelet function was quantified by measuring thrombin generation rates using innovative assaying techniques. The measurements were conducted with the stenosis models mounted in a flow loop driven by a computerized pump capable of producing physiologically relevant flow curves. Both eccentric and axi-symmetric stenosis models with varying degrees of stenosis were employed. These geometries enabled to study the hemodynamic effects under well-controlled flow parameters; the size of the recirculation region, the locations of the separation and reattachment points as a function of the Reynolds number, and steady vs. pulsatile flow conditions. The flow through the stenosis geometry generated contraction and curvature of streamlines, elevated shear and turbulent stresses, recirculation zones, and also periodic vortex shedding under certain conditions. The results presented depict the process by which pathological flow conditions may bring platelets beyond their activation threshold and induce thrombus formation in cardiovascular blood recirculating devices.