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Objective: Cardiac syndrome X (CSX) is of clinical interest, yet the underlying pathophysiological mechanisms have not been fully elucidated. It is well known that elevated blood viscosity and red blood cell (RBC) aggregation can adversely affect microcirculatory blood flow. The present study was designed to explore whether CSX is associated with abnormalities of blood rheology., Methods: Blood samples were obtained from 152 adult angina patients undergoing diagnostic coronary angiography; geometric and flow-velocity data were obtained. Rheologic measurements were performed in a blinded manner; 21 subjects were later identified with CSX. Hemorheologic and clinical laboratory data were compared to 21 age- and gender-matched healthy controls., Results: CSX patients had markedly abnormal blood rheology: (1) higher RBC aggregation and aggregability as judged by erythrocyte sedimentation rate and Myrenne indices at stasis and low shear (p < 0.001) and (2) elevated hematocrit-corrected blood viscosity, plasma viscosity (p < 0.001), and yield stress (p < 0.01). White blood cell counts and high-sensitivity C-reactive protein levels were significantly elevated in CSX; coronary-flow velocities were below normal., Conclusions: Abnormal hemorheologic parameters exist in subjects with CSX and may contribute to the pathophysiology of the disease, presumably via adversely affecting blood flow in the coronary microcirculation. Therapeutic measures aimed at normalizing blood rheology and hence microcirculatory flow should be explored.

Background: Color Doppler imaging (CDI) is the most applied method for evaluation of flow in atrial septal defects (ASD). A new real time ultrasound flow imaging modality called blood flow imaging (BFI) is able to visualize the blood flow in any direction of the image and is not limited by velocity aliasing. The method thereby overcomes the two limitations most often encountered in CDI. In this study we compared BFI with CDI for the visualization of interatrial blood flow in children., Methods: We studied ASD flow in 13 children using both CDI and BFI in the same examination. CDI and BFI cineloops were prepared off-line and both optimal and suboptimal (increased color artifacts) images were presented in random order to four observers. They were asked to range from 0-100 on a visual analogue scale how certain they were of interatrial blood flow. The CDI and BFI ratings were compared using the exact Wilcoxon signed rank test for paired samples., Results: All ASDs visualized with CDI were confirmed using BFI. Two of the observers ranked BFI as being significantly better than CDI when the images were optimized. When the images were suboptimal three of the observers rated BFI as being significantly better., Conclusions: This pilot study indicates that BFI improves the visualization of interatrial blood flow in children. To include BFI in the ordinary echocardiography examination is easy and not time consuming. The method may prove to be a useful supplement to CDI in ASD imaging.

The effect of elevated shear stress upon cellular trauma has been studied for many years, but the effect of long-term cyclic stress trauma on hemorheology has never been explored systematically. This study investigated sublytic trauma of red blood cells (RBCs) caused by repeated exposure to shear stress. A suspension of bovine blood was throttled through a capillary tube (inner diameter 1 mm and length 70 mm) connected to a recirculating flow loop. Samples were withdrawn every 30 min to measure deformability and characteristic time. The deformability of the cell was measured microscopically by observing the shape of the cell during the shear flow. It was found that cyclic shear irreversibly stiffened the cell membrane while the effect was not so much as that of continuous shear. The cell deformability was dramatically reduced by 73% when the stress of 300 Pa was applied for 288 s, while it was 7% under 90 Pa. These results elucidate the need for improved models to predict cellular trauma within the unsteady flow environment of mechanical circulatory assist devices.

We have developed a tiny rotary centrifugal blood pump for the purpose of supporting circulation of children and infants. The pump is designed to provide a flow of 0.1-4.0 L/min against a head pressure of 50-120 mm Hg. The diameter of the impeller is 30 mm with six straight vanes. The impeller is supported by a hydrodynamic bearing at its center and rotated with a radial coupled magnetic driver. The bearing that supports rotation of the impeller of the tiny centrifugal blood pump is very critical to achieve durability, and clot-free and antihemolytic performance. In this study, computational fluid dynamics (CFD) analysis was performed to quantify the secondary flow through the hydrodynamic bearing at the center of the impeller and investigated the effects of bearing clearance on shear stress to optimize hemolytic performance of the pump. Two types of bearing clearance (0.1 and 0.2 mm) were studied. The wall shear stress of the 0.1-mm bearing clearance was lower than that of 0.2-mm bearing clearance at 2 L/min and 3000 rpm. This was because the axial component of the shear rate significantly decreased due to the narrower clearance even though the circumferential component of the shear rate increased. Hemolysis tests showed that the normalized index of hemolysis was reduced to 0.0076 g/100 L when the bearing clearance was reduced to 0.1 mm. It was found that the CFD prediction supported the experimental trend. The CFD is a useful tool for optimization of the hydrodynamic bearing design of the centrifugal rotary blood pump to optimize the performance of the pump in terms of mechanical effect on blood cell elements, durability of the bearing, and antithrombogenic performance.

The magnetically levitated (Mag-Lev) centrifugal rotary blood pump (CRBP) with two-degrees-of-freedom active control is promising for safe and long-term support of circulation. In this study, Mag-Lev CRBP controllability and impeller behavior were studied in the simulated heart failure circulatory model. A pneumatically driven pulsatile blood pump (Medos VAD [ventricular assist device]-54 mL) was used to simulate the left ventricle (LV). The Mag-Lev CRBP was placed between the LV apex and aortic compliance tank simulating LV assistance. The impeller behavior in five axes (x, y, z, theta, and phi) was continuously monitored using five eddy current sensors. The signals of the x- and y-axes were used for feedback active control, while the behaviors of the other three axes were passively controlled by the permanent magnets. In the static mock circuit, the impeller movement was controlled to within +/-10-+/-20 microm in the x- and y-axes, while in the pulsatile circuit, LV pulsation was modulated in the impeller movement with the amplitude being 2-22 microm. The amplitude of impeller movement measured at 1800 rpm with the simulated failing heart (peak LV pressure [LVP] = 70 mm Hg, mean aortic pressure [AoP(mean)] = 55 +/- 20 mm Hg, aortic flow = 2.7 L/min) was 12.6 microm, while it increased to 19.2 microm with the recovered heart (peak LVP = 122 mm Hg, AoP(mean) = 100 +/- 20 mm Hg, aortic flow = 3.9 L/min). The impeller repeated the reciprocating movement from the center of the pump toward the outlet port with LV pulsation. Angular rotation (theta, phi) was around +/-0.002 rad without z-axis displacement. Power requirements ranged from 0.6 to 0.9 W. Five-axis impeller behavior and Mag-Lev controller stability were demonstrated in the pulsatile mock circuit. Noncontact drive and low power requirements were shown despite the effects of LV pulsation. The impeller position signals in the x- and y-axes reflected LV function. The Mag-Lev CRBP is effective not only for noncontact low power control of the impeller, but also for diagnosis of cardiac function noninvasively.

A detailed knowledge of the flow field in a blood pump is indispensable in order to increase the efficiency of the pump and to reduce the shear-induced hemolysis. Thus, three different impeller designs were developed and tested by means of computational fluid dynamics (CFD) and digital particle image velocimetry (DPIV). The results show a good agreement of CFD and DPIV data. An optimization of the impeller could be achieved by following the concept of turbulent drag reduction for the axisymmetric center body.

The aim of this work is to construct a computational fluid dynamics model capable of simulating the quasitransient process of apheresis. To this end a Lagrangian-Eulerian model has been developed which tracks the blood particles within a delineated two-dimensional flow domain. Within the Eulerian method, the fluid flow conservation equations within the separator are solved. Taking the calculated values of the flow field and using a Lagrangian method, the displacement of the blood particles is calculated. Thus, the local blood density within the separator at a given time step is known. Subsequently, the flow field in the separator is recalculated. This process continues until a quasisteady behavior is reached. The simulations show good agreement with experimental results. They shows a complete separation of plasma and red blood cells, as well as nearly complete separation of red blood cells and platelets. The white blood cells build clusters in the low concentrate cell bed.

The effects of variations in the venous valve anatomy are studied experimentally using an artificial system that mimics the bicuspid valves normally found in veins in the lower extremities. The artificial valves are constructed from thin-walled, latex tubing and polyurethane film. The experimental variables in the study are the gap width between the leaflet attachments at the vein wall and the ratio of the sinus depth to vein diameter. The results show that the antegrade mass flow rate is not affected to the same degree when compared to retrograde flow by the various valve configurations examined in this study. The results also indicate that increases in the gap width, which serve to increase the degree of imperfect wall attachment, have less effect on retrograde mass flow rate in valves with deeper sinuses.

Central venous catheters are widely used as a hemoaccess method for dialysis therapy. In this study, the performance parameters (velocities, pressure drop, shear rates, access recirculation) of the Niagara catheter are analyzed using computational fluid dynamics. Side holes are left open, closed, or reduced in size to assess the influence of this design feature. Initially the catheter is inserted in a tube which represents the vena cava. In the "arterial" luminal tip, wall shear rates over 20,000 s(-1) are common and peaks attain 55,000 s(-1) at a 300 mL/min blood flow rate. The presence of side holes appears to affect the location but not the level of these elevated shear rates. Halving their diameter causes elevated shear rates to appear in a more extended region with peaks up to 80,000 s(-1). Simulated recirculation percentage is nil in normal catheter use, but attains 30% with reversed catheter connections. The results of the tube model are compared to those of an anatomically realistic right atrium model, which was three-dimensionally reconstructed. It is concluded that most catheter's specific hemodynamic properties can be deduced from the tube model.

Flow visualization experiments and computational fluid dynamic (CFD) analyses were performed and the results were compared to clarify the detailed fluid dynamic characteristics for the prototype design of a centrifugal pump, namely, an implantable ventricular assist system from Sun Medical, whose hemocompatibility was previously demonstrated in a series of animal experiments. The flow visualization was conducted with particle tracking velocimetry, and the CFD analysis was performed with STAR-CD software. The findings were as follows: (1). There were no flow separations around the curved open impeller. (2). Antithrombogenic design concepts for the inducer and the vane-shaft clearance were effective in producing axial velocity along the shaft surface and generat-ing suitable shear rates against the stationary fluid. (3). Unsteady vortex shedding in the outlet, which adversely affected the fluid dynamic efficiency, was observed clearly by flow visualization. Comparison of velocity distribution measured by flow visualization and CFD analysis showed reasonably good correlation. Our findings indicate that the impeller is suitable for an implantable artificial heart. The techniques of flow visualization and CFD analysis are complementary evaluation tools in research and development efforts.

In the last decades a great number of in vitro studies have been conducted to improve the design and to understand the transvalvular flow patterns under steady-state and pulsating flow conditions. Steady-state tests are useful for studying the flow established upstream and downstream of the valve prosthesis in different flow conditions and, in particular, at the peak flow rate. In the present study, the particle image velocimetry (PIV) technique is employed to visualize the flow patterns in a precommercial model of a bi-leaflet mechanical heart valve prosthesis in a steady-state flow regime. The use of the PIV technique and a convenient test rig provide good conditions with which to investigate the whole flow field upstream and downstream of the valve. Velocity and vorticity maps are obtained for the flow passing through the prosthesis in different axial planes. A new and simple solution for the measurement test chamber is proposed. This innovative approach of observing the flow in staggered planes (other than diametrical planes) allows a flow analysis to be performed upstream and downstream of the valve in regions near the tube wall where it has the maximum potential for injury of the vessel's inner cell layer.

The purpose of this study was to eliminate fluid dynamic causes of thrombus formation for the monopivot magnetic suspension centrifugal pump under development with the aid of flow visualization as an indirect measurement tool for animal experiments. The formation of thrombus observed in early animal experiments was successfully overcome by combining the multiple washout holes at the center into a single hole, optimizing the hole diameter, and eliminating the pivot gap. Flow visualization was used to optimize the washout hole diameter influencing the flow around the pivot. In animal experiments flow visualization showed that the contours of thrombus corresponded to shear rates of 300 s(-1) or 1300-1700 s(-1). It was found that flow visualization is a useful technique to predict locations where low shear thrombi form and to optimize the pump design in the development stage.

The purpose of this study was to determine whether the inflammatory response in patients with Gaucher disease (GD) is accompanied by enhanced adhesiveness/aggregation of both red and white blood cells. Sixty patients with GD and matched controls were included. The degree of erythrocyte and leukocyte adhesiveness/aggregation was determined by using a simple slide test and image analysis. Patients with GD had significantly elevated concentrations of fibrinogen (328 vs. 262 mg/dl, P < 0.0001) and accelerated erythrocyte sedimentation rates (27 vs. 13 mm/H, P < 0.005). This was accompanied by a significantly enhanced degree of erythrocyte (75 vs. 85, P < 0.0001) and leukocyte (3.5 vs. 1.3, P < 0.002) adhesiveness/aggregation. The low-grade, smoldering, and subclinical internal inflammation in individuals with GD is accompanied by an increased degree of erythrocyte and leukocyte adhesiveness/aggregation. These findings might have rheological consequences in terms of microcirculatory slow flow and tissue hypoxemia., (Copyright 2004 Wiley-Liss, Inc.)

This article presents a computational fluid dynamics (CFD) model to analyze pulsatile blood flow in a human artery. The model assumes the vessel as being a straight wall tube, and the blood flow is considered to be incompressible, Newtonian, and axisymmetric. Physiologically realistic resting conditions were adopted for the simulation tests. The main objective was to identify regions where pulsatile effects were significant. Velocity profiles were obtained for both normal and stenosed vessels. The results have shown that, for normal vessels, pulsatile effects prevail close to the vessel wall. The presence of stenosed sections resulted in flow alterations, with flow recirculation areas changing both size and location during the cardiac cycle. These results are especially important in the design of artificial organs. The knowledge of the flow pattern in complex geometries such as artificial hearts, prosthetic valves, and ventricular assist devices can help avoid or minimize thrombogenesis and hemolysis.

This paper describes a procedure, based on Tikhonov regularization, for obtaining the shear rate function or equivalently the viscosity function of blood from Couette viscometry data. For data sets that include points where the sample in the annulus is partially sheared the yield stress of blood will also be obtained. For data sets that do not contain partially sheared points, provided the shear stress is sufficiently low, a different method of estimating the yield stress is proposed. Both the shear rate function and yield stress obtained in this investigation are independent of any rheological model of blood. This procedure is applied to a large set of Couette viscometer data taken from the literature. Results in the form of shear rate and viscosity functions and yield stress are presented for a wide range of hematocrits and are compared against those reported by the originators of the data and against independently measured shear properties of blood.

This paper describes a procedure, based on Tikhonov regularization, for extracting the shear stress versus shear rate relationship and yield stress of blood from capillary viscometry data. The relevant equations and the mathematical nature of the problem are briefly described. The procedure is then applied to three sets of capillary viscometry data of blood taken from the literature. From each data set the procedure computes the complete shear stress versus shear rate relationship and the yield stress. Since the procedure does not rely on any assumed constitutive equation, the computed rheological properties are therefore model-independent. These properties are compared against one another and against independent measurements. They are found to be in good agreement for shear stress greater than 0.1 Pa but show significant deviations for shear stress below this level. A possible way of improving this situation is discussed.