An in vivo investigation on the effects of stent implantation on hematological and hemorheological parameters.

BACKGROUND: Even though cardiovascular stenting is widely used for the treatment of coronary artery disease, information on how it can affect the hematological and hemorheological profile is scarce in the literature. Most of the work on this issue is based on theoretical or computational fluid dynamics models, lacking in-depth in vitro and in vivo experimental verification. OBJECTIVE: This work investigates, in an in vivo setting, the effects of stenting and the implantation time-course on hematological and hemorheological parameters that could potentially compromise the device's functionality and longevity. METHODS: Custom-made self-expanding nitinol stents were implanted in the common carotid artery of male CD1 mice. Whole blood samples were collected from control (non-stented) and stented animals at 5 and 10 weeks post-implantation. Hematological measurements and blood viscosity, red blood cell aggregation, and deformability were performed using standard techniques. RESULTS: Implant-induced changes were observed in some of the hematological and hemorheological indices. Blood viscosity seems to have been negatively affected by an increased hematocrit and reduced RBC deformability, at 10 weeks post-implantation, despite a slight decrease in RBC aggregation. CONCLUSIONS: Although the alterations observed may be the result of the peri-implant inflammatory response, the physiological consequences due to hemorheological changes need to be further investigated.

The effects of stenting on hemorheological parameters: An in vitro investigation under various blood flow conditions.

 Despite their wide clinical usage, stent functionality may be compromised by complications at the site of implantation, including early/late stent thrombosis and occlusion. Although several studies have described the effect of fluid-structure interaction on local haemodynamics, there is yet limited information on the effect of the stent presence on specific hemorheological parameters. The current work investigates the red blood cell (RBC) mechanical behavior and physiological changes as a result of flow through stented vessels. Blood samples from healthy volunteers were prepared as RBC suspensions in plasma and in phosphate buffer saline at 45% haematocrit. Self-expanding nitinol stents were inserted in clear perfluoroalkoxy alkane tubing which was connected to a syringe, and integrated in a syringe pump. The samples were tested at flow rates of 17.5, 35 and 70 ml/min, and control tests were performed in non-stented vessels. For each flow rate, the sample viscosity, RBC aggregation and deformability, and RBC lysis were estimated. The results indicate that the presence of a stent in a vessel has an influence on the hemorheological characteristics of blood. The viscosity of all samples increases slightly with the increase of the flow rate and exposure. RBC aggregation and elongation index (EI) decrease as the flow rate and exposure increases. RBC lysis for the extreme cases is evident. The results indicate that the stresses developed in the stent area for the extreme conditions could be sufficiently high to influence the integrity of the RBC membrane.

Red blood cell aggregate flux in a bifurcating microchannel.

Red blood cell aggregation plays a key role in microcirculatory flows, however, little is known about the transport characteristics of red blood cell aggregates in branching geometries. This work reports on the fluxes of red blood cell aggregates of various sizes in a T-shaped microchannel, aiming to clarify the effects of different flow conditions in the outlet branches of the channel. Image analysis techniques, were utilised, and moderately aggregating human red blood cell suspensions were tested in symmetric (∼50-50%) and asymmetric flow splits through the two outlet (daughter) branches. The results revealed that the flux decreases with aggregate size in the inlet (parent) and daughter branches, mainly due to the fact that the number of larger structures is significantly smaller than that of smaller structures. However, when the flux in the daughter branches is examined relative to the aggregate size flux in the parent branch an increase with aggregate size is observed for a range of asymmetric flow splits. This increase is attributed to size distribution and local concentration changes in the daughter branches. The results show that the flow of larger aggregates is not suppressed downstream of a bifurcation, and that blood flow is maintained, for physiological levels of red blood cell aggregation.

Partitioning of red blood cell aggregates in bifurcating microscale flows.

Microvascular flows are often considered to be free of red blood cell aggregates, however, recent studies have demonstrated that aggregates are present throughout the microvasculature, affecting cell distribution and blood perfusion. This work reports on the spatial distribution of red blood cell aggregates in a T-shaped bifurcation on the scale of a large microvessel. Non-aggregating and aggregating human red blood cell suspensions were studied for a range of flow splits in the daughter branches of the bifurcation. Aggregate sizes were determined using image processing. The mean aggregate size was marginally increased in the daughter branches for a range of flow rates, mainly due to the lower shear conditions and the close cell and aggregate proximity therein. A counterintuitive decrease in the mean aggregate size was apparent in the lower flow rate branches. This was attributed to the existence of regions depleted by aggregates of certain sizes in the parent branch, and to the change in the exact flow split location in the T-junction with flow ratio. The findings of the present investigation may have significant implications for microvascular flows and may help explain why the effects of physiological RBC aggregation are not deleterious in terms of in vivo vascular resistance.

Numerical analysis of 3D blood flow and common carotid artery hemodynamics in the carotid artery bifurcation with stenosis.

The results for blood flow in the carotid artery bifurcation on the basis of numerical simulation of Navier-Stokes equations are presented in this study. Four cases of carotid bifurcation are considered: common carotid artery (CCA) bifurcation without stenoses and cases with one, two and three stenoses are also presented. The results are obtained by performing numerical simulations considering one pulse wave period based on the finite volume discretization of Navier-Stokes equations. The structures of the flow around the bifurcation are obtained and the deformation of the pulse wave from common carotid artery (CCA) to the internal carotid artery (ICA) and external carotid artery (ECA) is traced. The axial velocity and wall shear stress (WSS) distribution and contours are presented considering the characteristic time points. The results of the WSS distribution around the bifurcation allow a prediction of the probable sites of stenosis growth.

The effect of red blood cell aggregation on velocity and cell-depleted layer characteristics of blood in a bifurcating microchannel.

Red blood cell (RBC) aggregation is a multifaceted phenomenon, and whether it is generally beneficial or deleterious remains unclear. In order to better understand its effect on microvascular blood flow, the phenomenon must be studied in complex geometries, as it is strongly dependent on time, flow, and geometry. The cell-depleted layer (CDL) which forms at the walls of microvessels has been observed to be enhanced by aggregation; however, details of the characteristics of the CDL in complex regions, such as bifurcations, require further investigation. In the present study, a microchannel with a T-junction was used to analyze the influence of aggregation on the flow field and the CDL. Micro-PIV using RBCs as tracers provided high resolution cell velocity data. CDL characteristics were measured from the same data using a newly developed technique based on motion detection. Skewed and sharpened velocity profiles in the daughter branches were observed, contrary to the behavior of a continuous Newtonian fluid. RBC aggregation was observed to increase the skewness, but decrease the sharpening, of the velocity profiles in the daughter branches. The CDL width was found to be significantly greater, with a wider distribution, in the presence of aggregation and the mean width increased proportionally with the reciprocal of the fraction of flow entering the daughter branch. Aggregation also significantly increased the roughness of the interface between the CDL and the RBC core. The present results provide further insight into how RBC aggregation may affect the flow in complex geometries, which is of importance in both understanding its functions invivo, and utilizing it as a tool in microfluidic devices.

Fast response characteristics of red blood cell aggregation.

The present work reports on an important feature of the fast response dynamics of blood flow observed after abrupt changes of the shearing conditions: distinctive peak values in conductance and light reflection/transmission have been observed at short times after the abrupt changes in the shearing conditions and have been attributed to red blood cell (RBC) disorientation and shape changes. Optical shearing microscopy results from the present study show that this peak is directly related to the inter-cellular or inter-aggregate spacing, quantified as the plasma gaps present in the captured images. In order to provide a more in-depth understanding of the structural characteristics of blood subjected to abrupt changes in the flow conditions, normal human blood samples at hematocrits of 45, 35, 25 and 10% were sheared at 100 s(-1) and the shear then suddenly reduced to values decreasing from 60 to 0 s(-1). Results from the present study agree qualitatively and quantitatively with results previously reported in the literature: the hematocrit and the magnitude of the final shear rate affect the magnitude of the peak values. The characteristic peak time was mostly influenced by the cell concentration. It is suggested that aggregation forces may play a part in the process of the fast response structural and spatial rearrangements of RBC.

On the effect of dynamic flow conditions on blood microstructure investigated with optical shearing microscopy and rheometry.

Red blood cell (RBC) aggregation affects significantly the flow of blood at low shear rates. Increased RBC aggregation is associated with various pathological conditions; hence an accurate quantification and better understanding of the phenomenon is important. The present study aims to improve understanding of the effect of dynamic flow conditions on aggregate formation; whole blood samples from healthy volunteers, adjusted at 0.45 haematocrit were tested in different flow conditions with a plate-plate optical shearing system, image analysis, and a double-walled Couette rheometric cell. Results are presented in terms of aggregation index Aa, aggregate size index As and number of aggregates, which are shown to vary with shear rate gamma and with different shear rate variations with time gamma. The aggregation index Aa was observed to increase as the shear rate decreased between 10 and 3 s(-1). Above 10 s(-1), Aa was found to have a minimum value indicating minimal aggregation while, at approximately 3 s(-1), Aa reaches a maximum. The aggregation size index As, the number of aggregates, and the blood viscosity were found to vary considerably when the same sample was examined over the same shear rate range, but for different variations of shear rate with time, gamma.