Biorheology

BACKGROUND: Blood flow in stenotic vessels strongly influences the progression of vascular diseases. Plaques in stenotic blood vessels vary in stiffness, which influences plaque behavior and deformation by pressure and flow. Concurrent changes in plaque geometry can, in turn, affect blood flow conditions. Thus, simultaneous studies of blood flow and plaque deformation are needed to fully understand these interactions.

OBJECTIVES: This study aims to identify the change of flow conditions attendant to plaque deformation in a model stenotic vessel.

METHODS: Three plaques of differing stiffness were constructed on a vessel wall using poly (vinyl alcohol) hydrogels (PVA-H) with defined stiffness to facilitate simultaneous observations of blood flow and plaque deformation. Flow patterns were observed using particle image velocimetry (PIV).

RESULTS: Decreases in Reynolds number (Re) with increased plaque deformation suggest that velocity decrease is more critical to establishment of the flow pattern than expansion of the model lumen. Upon exiting the stenosis, the location of the flow reattachment point, shifted further downstream in all models as plaque stiffness decreased and depended on the increase in upstream pressure.

CONCLUSIONS: These results suggest that in addition to luminal area, plaque stiffness should be considered as a measure of the severity of the pathology.

BACKGROUND: In microcirculation, the non-Newtonian behavior of blood and the complexity of the microvessel network are responsible for the high flow resistance and the large reduction of the blood pressure. Red blood cell aggregation along with inward radial migration are two significant mechanisms determining the former. Yet, their impact on hemodynamics in non-straight vessels is not well understood.

OBJECTIVE: In this study, the steady state blood flow in stenotic rigid vessels is examined, employing a sophisticated non-homogeneous constitutive law. The effect of red blood cells migration on the hydrodynamics is quantified and the constitutive model’s accuracy is evaluated.

METHODS: A numerical algorithm based on the two-dimensional mixed finite element method and the EVSS/SUPG technique for a stable discretization of the mass and momentum conservation equations in addition to the constitutive model is employed.

RESULTS: The numerical simulations show that a cell-depleted layer develops along the vessel wall with an almost constant thickness for slow flow conditions. This causes the reduction of the drag force and the increase of the pressure gradient as the constriction ratio decreases.

CONCLUSIONS: Viscoelastic effects in blood flow were found to be responsible for steeper decreases of tube and discharge hematocrits as decreasing function of constriction ratio.

BACKGROUND: The analysis of cell separation has many important biological and medical applications. Dielectrophoresis (DEP) is one of the most effective and widely used techniques for separating and identifying biological species.

OBJECTIVE: In the present study, a DEP flow channel, a device that exploits the differences in the dielectric properties of cells in cell separation, was numerically simulated and its cell-separation performance examined.

METHODS: The samples of cells used in the simulation were modeled as human leukocyte (B cell) live and dead cells. The cell-separation analysis was carried out for a flow channel equipped with a planar electrode on the channel’s top face and a pair of interdigitated counter electrodes on the bottom. This yielded a three-dimensional (3D) nonuniform AC electric field in the entire space of the flow channel.

RESULTS: To investigate the optimal separation conditions for mixtures of live and dead cells, the strength of the applied electric field was varied. With appropriately selected conditions, the device was predicted to be very effective at separating dead cells from live cells.

CONCLUSIONS: The major advantage of the proposed method is that a large volume of sample can be processed rapidly because of a large spacing of the channel height.

BACKGROUND: Cytoskeletal stress fibers (SFs) play important roles in cell rheology. Oxidative stress, as caused by excessive hydrogen peroxide (H₂O₂) or other reactive oxygen species, can cause cell damages via multiple pathways. Stress fiber mechanics in an oxidative environment is important for the understanding of such pathological challenges.

OBJECTIVE: This investigation aimed to assess the effects of oxidative stress on the mechanical conditions of single stress fibers in living cells.

METHODS: Utilizing a femtosecond (fs) laser to sever single SFs inside living C2C12 myoblasts, we investigated the retraction rheology of the severed single SFs to probe the mechanical conditions of the cells and the effect of H₂O₂ on them.

RESULTS: The equilibration time of the retraction of the severed SFs became longer in the H₂O₂-treated myoblasts compared to the control. The initial gap between the two severed ends of the SF immediately after fs laser severing was larger in the H₂O₂-treated groups. This suggested that H₂O₂ exposure could promote the pre-stress in individual SFs in-situ.

CONCLUSION: Oxidative stress could significantly affect the mechanical conditions of cytoskeletal SFs in myoblasts. The results were consistent with cell stiffness measured on single myoblasts under oxidative stress.

BACKGROUND: Deep vein thrombosis and the risk of pulmonary embolism are significant causes of morbidity and mortality. Much remains unclear, however, about the mechanisms by which a venous thrombus initiates, progresses, or resolves. In particular, there is a pressing need to characterize the evolving mechanical properties of a venous thrombus for its mechanical integrity is fundamental to many disease sequelae.

OBJECTIVE: The primary goal of the present study was to initiate a correlation between evolving histological changes and biomechanical properties of venous thrombus.

METHODS: We employed an inferior vena cava ligation model in mice to obtain cylindrical samples of thrombus that were well suited for mechanical testing and that could be explanted at multiple times following surgery. Using uniaxial micro-mechanical testing, we collected stress–stretch data that were then fit with a microstructurally-inspired material model before submitting the samples to immunohistological examination.

RESULTS: We found that venous thrombus underwent a radially inward directed replacement of fibrin with collagen between 2 weeks and 4 weeks of development, which was accompanied by the infiltration of inflammatory and mesenchymal cells. These histological changes correlated with a marked increase in material stiffness.

CONCLUSIONS: We demonstrated that 2 to 4 week old venous thrombus undergoes drastic remodeling from a fibrin-dominated mesh to a collagen-dominated microstructure and that these changes are accompanied by dramatic changes in biomechanical behavior.