The need to optimize the thrombogenic performance of blood recirculating cardiovascular devices, e.g., prosthetic heart valves (PHV) and ventricular assist devices (VAD), is accentuated by the fact that most of them require lifelong anticoagulation therapy that does not eliminate the risk of thromboembolic complications. The formation of thromboemboli in the flow field of these devices is potentiated by contact with foreign surfaces and regional flow phenomena that stimulate blood clotting, especially platelets. With the lack of appropriate methodology, device manufacturers do not specifically optimize for thrombogenic performance. Such optimization can be facilitated by formulating a robust numerical methodology with predictive capabilities of flow-induced platelet activation. In this study, a phenomenological model for platelet cumulative damage, identified by means of genetic algorithms (GAs), was correlated with in vitro experiments conducted in a Hemodynamic Shearing Device (HSD). Platelets were uniformly exposed to flow shear representing the lower end of the stress levels encountered in devices, and platelet activity state (PAS) was measured in response to six dynamic shear stress waveforms representing repeated passages through a device, and correlated to the predictions of the damage accumulation model. Experimental results demonstrated an increase in PAS with a decrease in "relaxation" time between pulses. The model predictions were in very good agreement with the experimental results.A recognized feature of the complex interplay regulating the pathogenesis of thrombosis is the effect of blood flow-induced mechanical forces on platelets. Physical agonists, such as these flow-induced forces, and chemical agonists, such as adenosine diphosphate and serotonin, trigger platelet activation. This process commences with the secretion of procoagulant and selfstimulating substances from granules, 1 which catalyze thrombin production. 2 As a direct consequence of activation, the platelets undergo a change in shape, marked by pseudopod extension. This increases the strength of adhesion to exogenous surfaces and decreases the resistance to aggregation.One of the major culprits in blood recirculating devices is the emergence of nonphysiologic (pathologic) flow patterns that enhance the hemostatic response. Elevated flow stresses that are present in the nonphysiologic geometries of blood recirculating devices enhance their propensity to initiate thromboembolism. In recent years, it has been demonstrated that flow induced thrombogenicity, caused by chronic platelet activation and the initiation of thrombus formation, is the salient aspect of mechanically induced blood trauma in devices. 3 This lends itself to the hypothesis that thromboembolism in prosthetic blood recirculating devices is

AbstFact--In this study, we analyzed blood flow through a model stenosis with Reynolds numbers ranging from 300 to 3,600 using both experimental and numerical methods. The jet produced at the throat was turbulent, leading to an axisymmetric region of slowly recirculating flow. For higher Reynolds numbers, this region became more disturbed and its length was reduced. The numerical predictions were confirmed by digital particle image velocimetry and used to describe the fluid dynamics mechanisms relevant to prior measurements of platelet deposition in canine blood flow (R. T. Schoephoerster et al., Atheroscleros& and Thromboshr 12:1806-1813. Actual deposition onto the wall was dependent on the wall shear stress distribution along the stenosis, increasing in areas of flow recirculation and reattachment. Platelet activation potential was analyzed under laminar and turbulent flow conditions in terms of the cumulative effect of the varying shear and elongational stresses, and the duration platelets are exposed to them along individual platelet paths. The cumulative product of shear rate and exposure time along a platelet path reached a value of 500, half the value needed for platelet activation under constant shear (J. M. Ramstack et al., Journal of Biomechanics 12: 113-125, 1979).

A model for platelet activation based on the theory of damage, incorporating cumulative effects of stress history and past damage (senescence) was applied to a three-dimensional (3-D) model of blood flow through a St. Jude Medical (SJM) bileaflet mechanical heart valve (MHV), simulating flow conditions after implantation. The calculations used unsteady Reynolds-averaged Navier-Stokes formulation with non-Newtonian blood properties. The results were used to predict platelet damage from total stress (shear, turbulent, deformation), and incorporate the contribution of repeated passages of the platelets along pertinent trajectories. Trajectories that exposed the platelets to elevated levels of stress around the MHV leaflets and led them to entrapment within the complex 3-D vortical structures in the wake of the valve significantly enhanced platelet activation. This damage accumulation model can be used to quantify the thrombogenic potential of implantable cardiovascular devices, and indicate the problem areas of the device for improving their designs.

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Patients who receive prosthetic heart valve (PHV) implants require mandatory anticoagulation medication after implantation due to the thrombogenic potential of the valve. Optimization of PHV designs may facilitate reduction of flow-induced thrombogenicity and reduce or eliminate the need for post-implant anticoagulants. We present a methodology entitled Device Thrombogenicty Emulator (DTE) for optimizing the thrombo-resistance performance of PHV by combining numerical and experimental approaches. Two bileaflet mechanical heart valves (MHV) designs -St. Jude Medical (SJM) and ATS were investigated, by studying the effect of distinct flow phases on platelet activation. Transient turbulent and direct numerical simulations (DNS) were conducted, and stress loading histories experienced by the platelets were calculated along flow trajectories. The numerical simulations indicated distinct design dependent differences between the two valves. The stress-loading waveforms extracted from the numerical simulations were programmed into a hemodynamic shearing device (HSD), emulating the flow conditions past the valves in distinct 'hot spot' flow regions that are implicated in MHV thrombogenicity. The resultant platelet activity was measured with a modified prothrombinase assay, and was found to be significantly higher in the SJM valve, mostly during the regurgitation phase. The experimental results were in excellent agreement with the calculated platelet activation potential. This establishes the utility of the DTE methodology for serving as a test bed for evaluating design modifications for achieving better thrombogenic performance for such devices.