To better understand the mechanisms leading to the formation and growth of mural thrombi on biomaterials, we have developed a two-dimensional computational model of platelet deposition and activation in flowing blood. The basic formulation is derived from prior work by others, with additional levels of complexity added where appropriate. It is comprised of a series of convection-diffusion-reaction equations which simulate platelet-surface and platelet-platelet adhesion, platelet activation by a weighted linear combination of agonist concentrations, agonist release and synthesis by activated platelets, platelet-phospholipid-dependent thrombin generation, and thrombin inhibition by heparin. The model requires estimation of four parameters to fit it to experimental data: shear-dependent platelet diffusivity and resting and activated platelet-surface and platelet-platelet reaction rate constants. The model is formulated to simulate a wide range of biomaterials and complex flows. In this article we present the basic model and its properties; in Part II (Sorensen et al., Ann. Biomed. Eng. 27:449-458, 1999) we apply the model to experimental results for platelet deposition onto collagen.

No abstract

This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re(throat)) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re(throat)=500) and turbulent flow conditions (Re(throat)≥3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of ∼10% at most of the locations. However, for the transitional flow case (Re(throat)=2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to ∼60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to ∼15%. The experimental procedure and flow results from this interlaboratory study (available at http://fdacfd.nci.nih.gov) will be useful in validating CFD simulations of the benchmark nozzle model and in performing PIV studies on other medical device models.

Experimental and computational studies were performed to elucidate the role of turbulent stresses in mechanical blood damage (hemolysis). A suspension of bovine red blood cells (RBC) was driven through a closed circulating loop by a centrifugal pump. A small capillary tube (inner diameter 1 mm and length 70 mm) was incorporated into the circulating loop via tapered connectors. The suspension of RBCs was diluted with saline to achieve an asymptotic apparent viscosity of 2.0 +/- 0.1 cP at 23 degrees C to produce turbulent flow at nominal flow rate and pressure. To study laminar flow at the identical wall shear stresses in the same capillary tube, the apparent viscosity of the RBC suspension was increased to 6.3 +/- 0.1 cP (at 23 degrees C) by addition of Dextran-40. Using various combinations of driving pressure and Dextran mediated adjustments in dynamic viscosity Reynolds numbers ranging from 300-5,000 were generated, and rates of hemolysis were measured. Pilot studies were performed to verify that the suspension media did not affect mechanical fragility of the RBCs. The results of these bench studies demonstrated that, at the same wall shear stress in a capillary tube, the level of hemolysis was significantly greater (p < 0.05) for turbulent flow as compared with laminar flow. This confirmed that turbulent stresses contribute strongly to blood mechanical trauma. Numerical predictions of hemolysis obtained by computational fluid dynamic modeling were in good agreement with these experimental data.