Biorheology

Regardless of the mechanisms that initiate the increase in blood pressure, functional and structural changes in the systemic vasculature are the final result of long-standing hypertension. These changes can occur in the macro- but also in the microvasculature. The supply of the tissues with oxygen, nutrients, and metabolites occurs almost exclusively in the microcirculation (which comprises resistance arterioles, capillaries and venules), and an adequate perfusion via the microcirculatory network is essential for the integrity of tissue and organ function.

This review focuses on results from clinical studies in hypertensive patients, which have been performed in close cooperation with different clinical groups over the last three decades. Intravital microscopy was used to study skin microcirculation, microcatheters for the analysis of skeletal muscle microcirculation, the slit lamp for conjunctival microcirculation and the laser scanning ophthalmoscope for the measurement of the retinal capillary network.

The first changes of the normal microcirculation can be found in about 93% of patients with essential hypertension, long before organ dysfunctions become clinically manifest. The earliest disorders were found in skin capillaries and thereafter in the retina and the skeletal muscle. In general, the disorders in the different areas were clearly correlated. While capillary rarefaction occurred mainly in the retina and the conjunctiva bulbi, in skin capillaries morphological changes were rare. A significant decrease of capillary erythrocyte velocities under resting conditions together with a marked damping of the postischemic hyperemia was found, both correlating with the duration of hypertension or WHO stage or the fundus hypertonicus stage. Also the mean oxygen tension in the skeletal muscle was correlated with the state of the disease.

These data show that the microcirculatory disorders in hypertension are systemic and are hallmarks of the long-term complications of hypertension. There is now a large body of evidence that microvascular changes occur very early and may be important in their pathogenesis and progression.

The study of hemodynamics in an animal model simulating coronary stenosis has been limited due to the lack of a safe, accurate and reliable technique for creating an artificial stenosis. Creating artificial stenosis using occluders in an open-chest procedure has often caused myocardial infarction (MI) or severe injury to the vessel resulting in high failure rates. To minimize these issues, closed-chest procedures with internal balloon obstruction are often used to create an artificial stenosis. However, the hemodynamics in a blood vessel with internal balloon obstruction versus a physiological stenosis has not been compared. Hence, the aim of this research is to develop a relationship to predict the balloon obstruction equivalent to that of a physiological stenosis. The pressure drop in a balloon obstruction was evaluated and compared with that in a physiological stenosis. It was observed that the flow characteristics in balloon obstructions are more viscous dominated, whereas those in physiological stenoses are momentum dominated. Balloon radius was iteratively varied using a Design of Experiments (DOE) based optimization method to obtain a pressure drop equal to that of a physiological stenosis at mean hyperemic flow rates. A linear relation was obtained to predict equivalent balloon obstruction for a physiological stenosis. Further, the details were verified with our in vivo (animal) study data.

We investigated experimentally the rheological behavior of whole human blood subjected to large amplitude oscillatory shear under strain control to assess its nonlinear viscoelastic response. In these rheological tests, the shear stress response presented higher harmonic contributions, revealing the nonlinear behavior of human blood that is associated with changes in its internal microstructure. For the rheological conditions investigated, intra-cycle strain-stiffening and intra-cycle shear-thinning behavior of the human blood samples were observed and quantified based on the Lissajous–Bowditch plots. The results demonstrated that the dissipative nature of whole blood is more intense than its elastic component. We also assessed the effect of adding EDTA anticoagulant on the shear viscosity of whole blood subjected to steady shear flow. We found that the use of anticoagulant in appropriate concentrations did not influence the shear viscosity and that blood samples without anticoagulant preserved their rheological characteristics approximately for up to 8 minutes before coagulation became significant.

The AC electric field-driven manipulation of suspended polarizable particles has become a major technique in micro- and nano-devices. In the present study, suspensions of cultured HeLa cells in isotonic solution were used to explore the mechanisms underlying the suspension behaviors during exposure to a uniform AC electric field of strength E_rms=1.67×10⁴ V/m at frequency 1 kHz. Molecular dynamics (MD) simulations based on the Langevin equation of particle kinetics were performed to elucidate the corresponding problem. A theoretical model to compute the trajectories of individual cells under the action of electro-mechanical, viscous and gravitational forces in the suspending medium was newly developed. Numerical computations demonstrated that the suspended cells began to aggregate to form chainlike clusters along the direction of the uniform AC electric field at an earlier stage of the field application. Moreover, the predicted results were similar to the experimental results. These findings indicate that the chain-like cell clustering arises from the long-range dipole–dipole interaction of neighboring cells, but under the action of the gravitational force that likely hinders the growth of clusters in the vertical direction.

The observation that the fluidity must remain within a critical interval, outside which the stability and functionality of the cell tends to decrease, shows that stability, fluidity and function are related and that the measure of erythrocyte stability allows inferences about the fluidity or functionality of these cells. This study determined the biochemical and hematological variables that are directly or indirectly related to erythrocyte stability in a population of 71 volunteers. Data were evaluated by bivariate and multivariate analysis. The erythrocyte stability showed a greater association with hematological variables than the biochemical variables. The RDW stands out for its strong correlation with the stability of erythrocyte membrane, without being heavily influenced by other factors. Regarding the biochemical variables, the erythrocyte stability was more sensitive to LDL-C. Erythrocyte stability was significantly associated with RDW and LDL-C. Thus, the level of LDL-C is a consistent link between stability and functionality, suggesting that a measure of stability could be more one indirect parameter for assessing the risk of degenerative processes associated with high levels of LDL-C.