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Interaction forces, deformation and nano-rheology of individual red blood cells in physiologically relevant solution conditions have been determined by colloid probe atomic force microscopy (AFM). On approach of the physically immobilised cell and silica glass spherical probe surfaces, deformation of the red blood cell was observed in the force curves. At low levels of deformation, spring constants were determined in the range 3-6 m Nm(-1), whereas for higher levels of deformation, the forces increase non-linearly and on retraction, significant force curve hysteresis is observed (i.e. lower forces upon retraction). The extent of force curve hysteresis was dependent on both the drive velocity and loading force, typical of a viscoelastic system. The response of the red blood cell has been described by viscoelastic theory, where the short and long time scale elastic moduli and relaxation times are determined, i.e. the cell's nano-rheological properties elucidated. In addition to a time independent elastic modulus of 4.0 x 10(3)Nm(-2) at low levels of deformation, time-dependent elastic moduli ranges are observed (3.5 x 10(4) to 5.5 x 10(4)Nm(-2) at intermediate levels of deformation and 1.5 x 10(5) to 3.0 x 10(5)Nm(-2) at higher levels of deformation). That is, one elastic and more than one viscoelastic response to the red blood cell deformation is evident, which is considered to reflect the cellular structure.

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.

Platelet-monocyte binding and surface P-selectin expression are sensitive markers of platelet activation. Endothelium-derived factors are known to inhibit platelet activation and may confer important anti-atherothrombotic effects. We assessed the relationship between platelet activation and endothelium-dependent vasomotion in patients with coronary heart disease (CHD). Twenty male patients with stable CHD were compared with 20 healthy men. Platelet-monocyte binding and platelet surface expression of P-selectin were assessed using two-colour flow cytometry on whole blood. Forearm blood flow was assessed in patients using venous occlusion plethysmography during intra-arterial infusions of substance P, acetylcholine and sodium nitroprusside. Platelet activation was higher in patients than healthy men (platelet-monocyte binding, 27 +/- 3 vs. 20 +/- 1%; P < 0.05). In patients with CHD, there was an inverse correlation between maximal substance P induced vasodilatation and both platelet-monocyte binding (P = 0.003) and P-selectin expression (P = 0.02). A similar correlation was observed between platelet-monocyte binding and the vasomotor response to acetylcholine (P = 0.08) but not with sodium nitroprusside. In patients with stable coronary heart disease, there is a strong inverse relationship between markers of platelet activation and endothelium-dependent vasomotor function. This may explain the pathophysiological mechanism linking endothelial vasomotor dysfunction and the risk of acute atherothrombotic events.

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.

To routinely test the formation of thrombi and the effect of drugs modifying it, proper test systems are needed. Their design should rely on the laws of rheology and the physiology of laminar flow. To best model physiological or pathological shear conditions, parallel/linear and rotational type flow chambers are developed. We have compared the initial phase of platelet thrombus formation in a parallel plate flow chamber (PPC) and a cone-and-plate chamber (CPC) under von Willebrand dependent shear conditions. Blood was allowed to flow through human collagen type III surfaces at a shear rate of 1000 s(-1) for 150 s. Thrombus deposition was characterized by surface coverage, average area and height of thrombi. VWF distribution within thrombi was analyzed with confocal laser scanning microscopy. Reduced surface-specific platelet adhesion and aggregation (surface coverage and average thrombus size) were observed in CPC along with a significant increase in single platelet disappearance from the circulating blood. Our data suggest that the higher rate of platelet consumption in this device, as opposed to PPC, is limiting the adhesion to the surface. Consequently, surface-specific processes and aggregation in the flowing blood are both assessed using CPC, while comprehensive evaluation of surface-specific processes is best achieved with PPC. Therefore, the choice of chamber type as a diagnostic tool is purpose-dependent.

Background: The pressure recording analytical method (PRAM) is a method for real-time beat-to-beat quantification of peripheral blood flow based on the analysis of arterial waveform morphology. Since PRAM can be implemented in any conditions of flow, whether physiological or artificial, we assessed its accuracy in patients undergoing cardiac surgery during extracorporeal circulation (ECC), using the roller-pump device as the reference gold standard., Methods: We prospectively studied 32 patients undergoing elective coronary surgery. Flow values obtained by PRAM from the radial artery were compared with simultaneous values by thermodilution in physiological conditions of flow and with the roller-pump device readings during ECC., Results: Before and after ECC, the overall estimates of flow measured by PRAM closely agreed with thermodilution (mean difference 0.07 +/- 0.40 L/min). During ECC, PRAM estimates of flow also closely correlated with simultaneous pump readings (mean difference 0.11 +/- 0.33 L/min). At time of weaning from ECC, two patterns of hemodynamic adaptation were documented by PRAM following resumption of cardiac contraction: in most patients (n =26; 80%), cardiac output (CO) was stable (reduction < or = 10% compared to the steady ECC phase); six patients (20%) showed a fall in CO exceeding 10% and up to 38%., Conclusions: PRAM provided accurate, continuous quantification of peripheral blood flow during each phase of cardiac surgery, including ECC, and allowed early recognition of patients with low CO during weaning from the pump.

This paper presents a new method for the visualization of two-dimensional (2-D) blood flow in ultrasound imaging systems called blood flow imaging (BFI). Conventional methods of color flow imaging (CFI) and power Doppler (PD) techniques are limited as the velocity component transversal to the ultrasound beam cannot be estimated from the received Doppler signal. The BFI relies on the preservation and display of the speckle pattern originating from the blood flow scatterer signal, and it provides qualitative information of the blood flow distribution and movement in any direction of the image. By displaying speckle pattern images acquired with a high frame rate in slow motion, the blood flow movement can be visually tracked from frame to frame. The BFI is easily combined with conventional CFI and PD methods, and the resulting display modes have been shown to have several advantages compared to CFI or PD methods alone. Two different display modes have been implemented: one combining BFI with conventional CFI, and one combining BFI with PD. Initial clinical trials have been performed to assess the clinical usefulness of BFI. The method especially has potential in vascular imaging, but it also shows potential in other clinical applications.

Blood rheology was considered to be of limited clinical importance, until extracorporeal technologies enabling the treatment of cellular and plasmatic hyperviscosity syndromes were introduced. However, a wide range of applications, mainly referring to rheologically determined diseases of the microcirculation exists but has so far hardly been taken into consideration. The extension of indications was due to modern technical developments leading to different approaches of secondary separation such as precipitation, ad- or absorption and filtration. Based on 18 years of experience with different separation technologies the combination of some centrifugal devices applied for cell--plasma separation with secondary filtration (Rheohemapheresis) appears to be the most efficacious and economical approach for such extracorporeal treatments. The sequence and frequency of rheohaemapheresis treatments depends on the measurement of rheological measurements in combination with clinical--chemical data which are related to the distribution kinetics and synthesis rate of both blood cells and plasma proteins. Standardised treatment protocols proved the efficacy of initial therapies and were applied for controlled trials whereas long term therapies may need more flexible treatment approaches. So far an increasing experience exists for the treatment of ophthalmologic diseases, otologic disorders, diabetic complications and cardiological diseases. Rheohemapheresis was shown to be a safe treatment approach, if a careful risk assessment prior to the initiation of the therapies is performed. The treatment cannot cure diseases but enables a substantial improvement of the quality of life in patients without treatment alternatives.

We have made the diagnosis of transcapillary flow disturbances in the lungs of lung cancer patients with the available noninvasive method of videobiomicroscopy of eye conjunctiva with further morphometric processing of obtained data using PC. 77 patients with lung cancer have been studied. Using videobiomicroscopy we calculated the size of venous capillary sacculations, the square of capillary glomerules (Sg), the amplitude (A), the 'length' of the twisted part of a microvessel (Lt), the amplitude-length coefficient (Ca), the frequency-length coefficient (Cf), the size of venous capillaries (V), intravascular conglomeration of aggregated erythrocytes (conglomerate), RBC aggregation coefficient (Cs) and the degree of sludge. To evaluate the data obtained, a comparative morphologic investigation of histologic samples taken from the intact areas of the lung parenchyma has been carried out. We diagnosed moderate or determined disturbances in the capillary flow that were confirmed by microscopy.

The rheologic characteristics of blood and its formed elements continue to be of basic science and clinical interest, with numerous publications dealing with topics such as blood and plasma viscosity, RBC aggregation and cell deformability. Alterations of blood's rheologic behavior in pathologic states have been extensively studied, with the findings usually indicating changes assumed to be detrimental to tissue perfusion (e.g., increased RBC aggregation). However, the current literature contains relatively few studies dealing with two important areas: (1) relations between altered rheologic behavior and in vivo hemodynamics; (2) the effects of therapy in those clinical states associated with altered rheologic behavior. This paper presents brief and selective comments on the assumed importance of two rheologic "abnormalities" (i.e., increased plasma viscosity, increased RBC aggregation), and on whether clinical therapy in diabetes, hypertension and sepsis leads to normalization of the "abnormalities". Finally, a few gratuitous comments are presented regarding possible future directions in the field of hemorheology and hemodynamics.

Background: Anemia of renal failure is primarily a problem of decreased RBC production due to erythropoietin deficiency. RBC survival is also reduced, perhaps due to decreased RBC deformability. This study measured blood viscosity over a range of shear rates in erythropoietin-treated patients on hemodialysis (HD), and compared the findings to matched patients with chronic renal insufficiency (CRI) and healthy controls., Methods: Four groups (control, CRI, non-diabetic HD, and diabetic HD) of 9 matched subjects were recruited. Blood viscosity was measured using a cone-plate viscometer over a variety of shear rates (11 to 225 s(-1))., Results: Control subjects had lower viscosity values throughout all shear rates when compared to the 3 renal disease groups (P value=0.039). A trend was observed to higher levels of renal function being associated with decreased blood viscosity in patients with CRI., Conclusions: Patients with kidney disease have increased blood viscosity at all shear rates. This may be related to changes in RBC shape and decreased deformability in patients with kidney disease, independent of HD- or DM-status. This may have implications for strategies to treat anemia in these patients.

Endothelial dysfunction is a systemic disorder with a key role in the pathogenesis of atherosclerosis and its complications. Current evidence suggests that endothelial status is not determined solely by the individual risk factor burden but is rather regarded as an integrated index of all atherogenic and atheroprotective factors present in an individual, including known as well as yet-unknown variables and genetic predisposition. Endothelial dysfunction reflects a vascular phenotype prone to atherogenesis and may therefore serve as a marker of the inherent atherosclerotic risk in an individual. Recent advances in the understanding of pathophysiology of early atherosclerosis have opened up new opportunities for development of methods for assessment of the earliest changes in the vessel wall. During the last decade some noninvasive techniques have been introduced in clinical practice among which the ultrasound assessment of flow-mediated vasodilation of the brachial artery is the most widely used. These stimuli induce the endothelium to release nitric oxide which causes vasodilation that can be visualized and measured as an index of the vasomotor activity. This technique is attractive because it is non-invasive, accessible and reproducible in everyday clinical practice.

Unlabelled: Obesity is associated with many comorbid pathologies that lead to increased morbidity and increased mortality. Hemorheological changes in obesity are currently investigated as one of the risk factors for many comorbid pathologies. It has been found that erythrocyte hyperaggregation and a decrease in erythrocyte filterability have also been well documented in obesity patients. The aim of this study is to present preliminary results of the influence of weight reduction after vertical banded gastroplasty (VBG) on aggregation of red cells and red blood cells deformability. We studied seven patients who underwent VBG, median age 46 years (range 35-52), median BMI 52.1 kg/m(2) (range 36.6-66). Blood rheology changes and selected biochemical parameters were examinated before and 6 months after VBG. Erythrocyte elongation and red blood cells (RBC) aggregation were measured using the Laser-assisted Optical Rotational Cell Analyser (LORCA). The RBC aggregation index was significantly decreased, while the aggregation half-time (t(1/2)) significantly elongated after surgery. The syllectogram amplitude did not change. No differences in RBC deformability were observed in the postoperative period., Conclusion: We could conclude that among morbidly obese patients six months after VBG some beneficial changes of erythrocyte rheological parameters are observed. Further studies are necessary to confirm our preliminary results.

The present study was designed to study RBC aggregability in type 1 and type 2 DM by a new method based on the dielectric properties of disperse systems. This dielectric method has a significantly higher sensitivity to detect enhanced RBC aggregation in DM than other methods. Aggregability is increased in type 1 DM and even more markedly in type 2 diabetic patients. The enhanced RBC aggregation in type 1 diabetes was significantly correlated with the levels of HbA(1C), cholesterol and triglycerides. However, no correlation between metabolic control and RBC aggregability was found in type 2 DM. The in vitro addition of non-toxic, low molecular weight dextran improves the high RBC aggregation in diabetes type 2. In the future, low molecular weight dextran may be used in DM patients clinically to lower the risk for vascular complications, after the problem of filtration is solved.

Measuring erythrocyte deformability with bulk filtrometers is common, but there are problems with standardization and sample quantity in small laboratory animals. In this study, blood was drawn from mice, rats, and dogs, and then erythrocyte suspensions at 1-5% hematocrit were prepared. Bulk filtrometers with a 5- or 3-microm pore-diameter filter were used to determine the initial relative filtration rate (IRFR) and relative cell transit time (RCTT). Hematological composition was also tested. In all species, the highest IRFR values occurred at 1% hematocrit, and the lowest values at 5%. In mice and rats, RCTT values were lowest at 1% and highest at 5% using a 5-microm filter, whereas in dogs, RCTT was elevated at 1-2%. Using a 3-microm filter, each species showed the same phenomena under 3%. RCTT values may become distorted above a certain cell-size/pore-size ratio. In mice and rats, 1% suspension is applicable for bulk filtrometry, but only using 5-microm filters., (Copyright 2006 Wiley-Liss, Inc.)

Previous studies showed that endothelial alterations caused by physical stress worsened the hemorheological parameters mainly in patients affected by ischemic vascular diseases: major vascular alterations have been found in patients with very high endothelial dysfunction indexes: these indexes are given by the various substances produced by the endothelium, but it is very difficult to have a value which clearly identifies the real state of the endothelial alteration. The function of the NO, an endogenous vasodilator whose synthesis is catalyzed by NOs, can be determined by the Citrulline/Arginine ratio, which represents the level of activity of the enzyme. A very good index of the endothelial dysfunction is asymmetric dimethylarginine (ADMA), a powerful endogenous inhibitor of NOs; in fact several studies have demonstrated a strong relationship between ischemic vascular disease and high levels of plasmatic ADMA. Our recent studies on heart failure and on ischemic cerebrovascular diseases evaluate endothelial dysfunctions and hemorheological parameters.

Sickle cell disease is characterized by vaso-occlusive episodes, mainly in the small vessels, resulting in tissue ischemia, multi-organ failure, and, occasionally, death. Hydroxyurea (HU) is an agent with important and effective role in the treatment of patients suffering from this disease. The purpose of this study was to estimate the effect of HU on the deformability of the red blood cell's membrane (RBCM) in an effort to possibly improve the rheological properties of the RBCs of patients with sickle cell anemia (SCA), as well as to investigate the mechanical and rheological properties of these cells using micropipette and filtration techniques. The rigidity index, IR, which is a measure of cell rigidity and the elastic shear modulus, mu, which is a measure of cell's membrane deformability (CMd), of the RBCs from normal subjects, used as normal controls, were found significantly lower as compared to those of patients with SCA, regardless the treatment with HU. Patients under treatment with HU exhibited values better than those of untreated patients, in both, IR as well as mu, although still worse than the values of normal controls.

Objectives: It has been shown that a hydroxyethylstarch solution significantly increases the aortic distensibility coefficient (ADC) as compared to other non-hydroxyethylstarch colloid solutions. In order to investigate whether the effect of hydroxyethylstarch on ADC is class-specific, we investigated the effect of two hydroxyethylstarch solutions (HES 200: Elohes and HES 240: Hesteril) on the ADC and compared them with two other colloid solutions: 5% albumin and fluid gelatin (Gelofusin) in a rabbit model of acute isovolumic hemodilution., Methods: Twenty-eight male New Zealand white rabbits were anesthetized and randomly allocated to receive (n=7, each): albumin, hydroxyethylstarch-200, hydroxyethylstarch-240 and gelatin for acute isovolumic hemodilution by exchanging 13 ml.kg(-1) body weight of blood with an identical volume of the test solution. Blood viscosity, mean arterial pressure, aortic blood flow and heart rate were measured and ADC was calculated., Results: All groups were comparable with respect to arterial pressure, heart rate and aortic blood flow velocity before and after isovolumic hemodilution. After hemodilution, ADC coefficient remained unchanged as compared with pre-hemodilution values with albumin, hydroxyethylstarch-240 and gelatin, whereas a sustained 3 fold increase was observed with hydroxyethylstarch-200., Conclusion: These results demonstrate that minor physicochemical differences between two hydroxyethylstarch solutions result in measurable differences in ADC and suggest that the clinical effects of colloids should probably be analyzed for each type of colloid and not for classes of colloids (e.g. hydroxyethylstarch or fluid gelatins).

Fluorescent microspheres have been used in multiple particle tracking studies. Our laboratory is working towards the use of fluorescent microsphere particle tracking in the study of the retinal circulation. The first stage of this project was to develop a technique for measurement and analysis of the particle tracking data. We intravenously injected 2.0 microm diameter, polystyrene microspheres, labeled with fluorescent dye, in anesthetized rats. Using a microscope with a fluorescence attachment, we viewed the fluorescent particles flowing through the surface vessels of the intestine. Data was recorded then analyzed frame by frame. The path of each microsphere was plotted on a transparency sheet and measured. Using a magnification ratio, the velocity and blood flow rate were calculated for 235 particles in five different blood vessels. We found this technique to be an effective method for studying blood flow in an arteriole. The results were comparable to other blood flow studies and showed characteristic trends of typical laminar blood flow.

The measurement of blood-plasma velocity distributions with spatial and temporal resolution in vivo is inevitable for the determination of shear stress distributions in complex geometries at unsteady flow conditions like in the beating heart. A non-intrusive, whole-field velocity measurement technique is required that is capable of measuring instantaneous flow fields at sub-millimeter scales in highly unsteady flows. Micro particle image velocimetry (muPIV) meets these demands, but requires special consideration and methodologies in order to be utilized for in vivo studies in medical and biological research. We adapt muPIV to measure the blood-plasma velocity in the beating heart of a chicken embryo. In the current work, bio-inert, fluorescent liposomes with a nominal diameter of 400 nm are added to the flow as a tracer. Because of their small dimension and neutral buoyancy the liposomes closely follow the movement of the blood-plasma and allow the determination of the velocity gradient close to the wall. The measurements quantitatively resolve the velocity distribution in the developing ventricle and atrium of the embryo at nine different stages within the cardiac cycle. Up to 400 velocity vectors per measurement give detailed insight into the fluid dynamics of the primitive beating heart. A rapid peristaltic contraction accelerates the flow to peak velocities of 26 mm/s, with the velocity distribution showing a distinct asymmetrical profile in the highly curved section of the outflow tract. In relation to earlier published gene-expression experiments, the results underline the significance of fluid forces for embryonic cardiogenesis. In general, the measurements demonstrate that muPIV has the potential to develop into a general tool for instationary flow conditions in complex flow geometries encountered in cardiovascular research.

Hypertension (HTA) and dyslipidemia (DLP) represent major risk factors for cardiovascular and cerebral-vascular ischemic disease. The mechanisms through which they can induce vascular damage are both metabolic and mechanical. Hemorheological alterations in HTA are result of changes affecting both red cell intrinsic structure and their interactions with the plasmatic components. Several hemorheological determinants (biochemical, ionic, metabolic and rheologic) could influence and produce an impaired erythrocyte deformability determining an increased flow resistance in the microcirculation. The "Erythrodeformeter" allows obtaining the stationary and dynamical linear parameters of erythrocyte membrane by laser diffractometry. Stationary and oscillatory shear-induced elongation of cells leads to an elliptical diffraction pattern, its geometric characteristics being directly related to those of deformed RBC. Erythrocyte stationary parameters (Deformability Index, surface viscosity and elastic modulus) were obtained in stationary regime. Complex viscoelastic parameters (dynamic elasticity, dynamic loss, viscous and elastic components of the complex viscosity) were obtained when operating in oscillating mode. The diffractometric method is sensitive to detect pathological or induced alterations on RBC membrane, which can affect blood flow in vivo. The rheological parameters obtained give important information about the erythrocyte membrane and allow to detect and characterize erythrocyte alterations in vascular pathologies.

To construct platelet substitutes that have hemostatic properties over a wide range of shear rates, we used fibrinogen gamma-chain carboxy-terminal sequence HHLGGAKQAGDV (H12), which recognizes activated platelets at low shear rates, and a recombinant water-soluble moiety of the platelet glycoprotein (rGPIbalpha), which recognizes von Willebrand factor at high shear rates. Three kinds of samples were prepared for this purpose: H12-conjugated latex beads (H12-latex beads), rGPIbalpha-latex beads, and H12/rGPIbalpha-latex beads. These samples were evaluated in thrombocytopenia-imitation blood at various flow conditions. Based on ADP-induced platelet aggregation studies, the H12-latex beads significantly enhanced platelet aggregation via H12 binding with GPIIb/IIIa activated on the surface of activated platelets, whereas the rGPIbalpha-latex beads did not support platelet aggregation. In the case of the H12/rGPIbalpha-latex beads, the function of H12 was suppressed by steric hindrance from the larger rGPIbalpha bound to the latex bead. A mixture of the H12-latex beads and the rGPIbalpha-latex beads adhered to a collagen surface over a wide range of shear rates. In particular, at high shear rates, a cooperative effect was observed in the enhancement of platelet thrombus formation compared with H12-latex beads or rGPIbalpha-latex beads alone. We propose that a mixed system of H12- and rGPIbalpha-conjugated nanoparticles is a more effective platelet substitute than each of the beads used alone and has enhanced platelet aggregation properties.

Rheological factors and increased platelet aggregation are convincingly implicated in the development of micro- and macrovascular disease associated with diabetes mellitus. The present examination has been designed to describe the effects of a standard oral glucose load on hemorheological parameters, platelet activation and aggregation in patients with normal and pathologic glucose tolerance. Oral glucose tolerance test (OGTT) was performed in 30 patients suspected to have diabetes mellitus. Hematocrit, erythrocyte aggregation, red blood cell filterability, plasma and whole blood viscosity, soluble P-selectin levels and platelet aggregation were tested paralelly with blood glucose measurements 1, 2, and 3 hours after glucose consumption. Patients were divided into two groups based on glucose tolerance. Patients with abnormal glucose tolerance (IGT/DM) showed significant elevation in red blood cell aggregability (Myrenne indices M and M1) at the 2- and 3-hour samplings (p<0.01 and p<0.001, respectively). Patients with normal glucose tolerance (NGT) showed significant elevation only in M1 index (p=0.01). Plasma viscosity decreased significantly compared to fasting values in IGT/DM patients in all samples, but remained unchanged in NGT patients. Hematocrit decreased in IGT/DM patients significantly from the 2-hour samplings on (p<0.05), in normoglycaemic patients its decrease reached a borderline significance at 3-hour measurements. No significant changes were detected in whole blood viscosity, red blood cell filterability and sP-selectin levels during OGTT in either examined groups. No examined parameters were significantly correlated to blood glucose levels at any sampling. Erythrocyte aggregation showed significant correlation with BMI (p<0.01). Our results demonstrate that after the intake of a standard amount of glucose the development of rheological alterations is not simultaneous with the elevation of blood glucose levels, and our data suggest that the observed elevation in erythrocyte aggregation during OGTT might be associated with hyperinsulinemia.

The rheological properties of erythrocytes: elongation and the aggregation, as well as basic peripheral blood parameters: RBC number, hematocrit, MCV, MCH, MCHC reticulocytes, fibrinogen level, ESR, and glucose level were studied in a group of erysipelas patients. The concentration of malonyl dialdehyde (MDA) in erythrocytes was also measured, as an indicator of oxidative stress exerted. The study involved 18 erysipelas patients and 18 healthy subjects. The rheological properties and the aggregation of erythrocytes were studied with the use of a LORCA instrument (Laser-assisted Optical Rotational Cell Analyser). Differences were found in elongation index (EI) between the blood control (C) and patients (P), with an increase of this value only at 0.58 Pa shear stress and at 1.13 Pa shear stress. Upstroke were used as the indexes of RBC deformability, and the following aggregation parameters: intensity of light scattering in the prior disaggregation (Isc dis) - C - 43.0 au (arbitrary units), P - 44.8 au, time when cells are round and not aggregated (Isc top) - C - 51.6 au, P - 49.3 au, the amplitude of aggregation, the difference between Isc max and Isc min (AMP) - C - 39.9 au, P - 28.7 au, aggregation index (AI) - C - 64.6%, P - 70.0%, time for reach one half of the maximum aggregation (t(1/2)) - C - 2.0 s, P - 1.5 s, threshold shear stress, the lowest force that breaks the aggregation formed (Y(thr)) in P exceed 170% control group were measured. A decrease in the elasticity of erythrocytes in erysipelas patients was associated with the simultaneous increase of MDA - C - 0.08 nM/mgHb, P - 0.11 nM/mgHb content in the membranes of red blood cells. Basic peripheral blood parameters studied in patients with erysipelas did not differ significantly from the control group except for WBC, fibrinogen (C - 3.8 g/l, P - 7.8 g/l), and ESR (C - 6.1 mm/h, P - 45.4 mm/h) which were significantly higher.

The electrorheological (ER) properties of blood indicate changes in the blood rheological behaviour due to imposition of electric field. The present work identifies and quantifies ER properties of blood at different shear rates and at different local structure of the flow field. A concurrent measurement system, based on a Contraves Low Shear 30 rotational rheometer was used in this study. It includes a pair of cylindrically shaped platinum electrodes, embedded into the wall of a resin replica of the Couette type flow chamber of the rheometer, constructed for conductivity measurement, and associated software (Data acquisition system). The relationship between the whole blood and plasma conductivity (the main active component of blood impedance) was studied in parallel with the changes in the rheological behaviour under steady and transient flow conditions. The time variation of blood conductivity at different flow regimes and the dependences of the apparent whole blood and plasma viscosity were investigated in the presence and absence of an electric field of 2 kHz. The results show that blood conductivity is strongly dependent on the blood factors considered and that any application using blood conductivity measurement should take into account the effect of flow, shear rates and hematocrit. The results also show that valuable information on the mechanical properties of blood can be obtained, in particular concerning the structuring and kinetics of "rouleaux formation".

The aim of the present study was the comparative analysis of the role of specific hemorheological derangements in the pathogenesis of ischemic brain infarcts with and without diabetes mellitus. Blood plasma viscosity, as well as red blood cells (RBC) aggregability were quantitatively investigated in all patients during the study. Both of the above mentioned indices of hemorheological disorders were significantly higher in the patients with brain infarcts and diabetes mellitus as compared to the control and the group of ischemic brain infarcts without diabetes. During the ischemic stroke, blood plasma viscosity was increased by a mean of 9.2 per cent in the first and by a mean of 17.6 per cent in the second group of patients. As to the erythrocyte aggregability index, it was changed considerably more - by a mean of 113.8 per cent during stroke without diabetes, while in the diabetic patients the RBC aggregability index was found to be increased by a mean of 147.3 per cent. Ischemic brain infarcts in patients with diabetes mellitus were associated with a significant increase of the patients' blood rheological disorders in all the investigated cases.

The study aimed at initial determination and analysis of selected rheological parameters of blood in the group of diabetics and patients after myocardial infarction and compare the results to the symptoms observed in thermographical studies. The parameters studied were: whole blood viscosity, plasma viscosity, relative blood viscosity and hematocrit value. A group of 60 subjects took part in the study. The control group (20 persons) included the healthy subjects who had never suffered from any circulatory system disorders and who did not receive any drugs affecting the hemorheological parameters. The group of diabetics included 18 patients and the group after myocardial infarction included 20 patients. Blood viscosity measurements were performed by means of a rotary-oscillatory reometer Contraves LS 40 at the decreasing shear rate ranging from 100-0.01 s(-1) during a period of 5 minutes. For each blood sample the hematocrit value was measured using the standard method. The plasma viscosity was calculated from the linear regression of the shear rate dependence of the shear stress measured by means of the Contraves LS 40 reometer.

The use of rheoencephalography (REG) in the clinical practice to evaluate cerebral blood flow is conditional on the finding of a method for removing the extracranial interference caused by the scalp blood flow. To remove this undesirable influence, digital processing based on statistics could be an effective technique if the appropriate data model were applied. This paper focuses on the analysis of the spatiotemporal features of the extracranial REG component, by comparing its morphology and phase shift at several scalp sites. For this purpose, a numerical model of the scalp was employed to assess tissue impedance changes caused by the inflow of a stepwise blood pulse wave. These results were compared with the experimental impedance waveforms recorded on six pairs of adjacent electrodes. The correlation coefficients between each pair of impedance recordings of each subject were always greater than 0.942, showing a mean value of 0.986. This result suggests that the extracranial REG component can be considered as morphologically invariant. On the other hand, negligible phase shifts were observed when mean electrode distances, measured in the blood flow direction, were relatively small, although temporal corrections in the data model would be advisable for longer distances.

Since the first successful implantation of a prosthetic heart valve four decades ago, over 50 different designs have been developed including both mechanical and bioprosthetic valves. Today, the most widely implanted design is the mechanical bileaflet, with over 170,000 implants worldwide each year. Several different mechanical valves are currently available and many of them have good bulk forward flow hemodynamics, with lower transvalvular pressure drops, larger effective orifice areas, and fewer regions of forward flow stasis than their earlier-generation counterparts such as the ball-and-cage and tilting-disc valves. However, mechanical valve implants suffer from complications resulting from thrombus deposition and patients implanted with these valves need to be under long-term anti-coagulant therapy. In general, blood thinners are not needed with bioprosthetic implants, but tissue valves suffer from structural failure with, an average life-time of 10-12 years, before replacement is needed. Flow-induced stresses on the formed elements in blood have been implicated in thrombus initiation within the mechanical valve prostheses. Regions of stress concentration on the leaflets during the complex motion of the leaflets have been implicated with structural failure of the leaflets with bioprosthetic valves. In vivo and in vitro experimental studies have yielded valuable information on the relationship between hemodynamic stresses and the problems associated with the implants. More recently, Computational Fluid Dynamics (CFD) has emerged as a promising tool, which, alongside experimentation, can yield insights of unprecedented detail into the hemodynamics of prosthetic heart valves. For CFD to realize its full potential, however, it must rely on numerical techniques that can handle the enormous geometrical complexities of prosthetic devices with spatial and temporal resolution sufficiently high to accurately capture all hemodynamically relevant scales of motion. Such algorithms do not exist today and their development should be a major research priority. For CFD to further gain the confidence of valve designers and medical practitioners it must also undergo comprehensive validation with experimental data. Such validation requires the use of high-resolution flow measuring tools and techniques and the integration of experimental studies with CFD modeling.

Background: Most large studies evaluating the diagnostic properties of access blood flow (Qa) in arteriovenous (AV) accesses have used the Transonic HD01 (Transonic Systems Inc, Ithaca, NY) device, and recommended thresholds for angiography are based on data from these studies. There has been little exploration of how the use of other devices might affect the feasibility or performance of screening in AV accesses., Methods: We compared 2 devices for measuring Qa: the Transonic HD01 and the Crit-Line TQA III (Hemametrics, Salt Lake City, UT). We studied 124 adults with end-stage renal disease and a functioning AV access (fistula or graft). Qa was measured with both devices in immediate succession during a single dialysis treatment. The primary outcome was the technical feasibility of the Qa measurement. We also compared mean Qa values measured by the Crit-Line III and Transonic devices., Results: Qa measurements were less likely to be technically feasible when the Crit-Line III device was used compared with the Transonic device (86.3% versus 100%; P < 0.001). In patients with valid measurements, mean Qa measured using the Crit-Line III was significantly less than that measured using the Transonic HD01 device (886 +/- 557 versus 1,148 +/- 685 mL/min; P < 0.001). The mean difference was 261 mL/min (95% confidence interval [CI], 117 to 405) and was greater at higher levels of Qa. On average, Qa measured by means of the Crit-Line III device was 73% as high as that measured using the Transonic device (95% CI, 63 to 84). There was poor agreement between devices about whether criteria for angiography were met (kappa < 0.1). The proportion of patients for whom angiography was indicated (based on results from the Crit-Line device) was significantly greater than when only results from the Transonic device were considered (40.3% versus 7.3%; P < 0.001)., Conclusion: Consideration should be given to device-specific Qa thresholds for angiography or, alternatively, standardization of Qa results between manufacturers. Clinicians should be aware that Qa results cannot be compared directly between different devices, and access monitoring should be performed using a single technique in any given patient. Additional studies are required before the Crit-Line TQA device can be recommended for widespread use.

Hemodynamic changes in intracranial aneurysms after stent placement include the appearance of areas with stagnant flow and low shear rates. We investigated the influence of stent placement on blood flow velocity and wall shear stress of an intracranial aneurysm using a finite element modeling approach. To assess viscosity changes induced by stent placement, the rheology of blood as non-Newtonian fluid was taken into account in this model. A two-dimensional model with a parent artery, a smaller branching artery, and an aneurysm located at the bifurcation, before and after stent placement, was used for simulation. Flow velocity plots and wall shear stress before and after stent placement was calculated over the entire cardiac circle. Values for dynamic viscosity were calculated with a constitutive equation that was based on experimental studies and yielded a viscosity, which decreases as the shear rate increases. Stent placement lowered peak velocities in the main vortex of the aneurysm by a factor of at least 4 compared to peak velocities in the main artery, and it considerably decreased the wall shear stress of the aneurysm. Dynamic viscosity increases after stent placement persisted over a major part of the cardiac cycle, with a factor of up to 10, most pronounced near the dome of the aneurysm. Finite element modeling can offer insight into rheological changes induced by stent treatment of aneurysms and allows visualizing dynamic viscosity changes induced by stent placement.

The long term patency of end-to-side peripheral artery bypasses are low due to failure of the graft generally at the distal end of the bypass. Both material mismatch between the graft and the host artery and junction hemodynamics are cited as being major factors in disease formation at the junction. This study uses experimental methods to investigate the major differences in fluid dynamics and wall mechanics at the proximal and distal ends for rigid and compliant bypass grafts. Injection moulding was used to produce idealized transparent and compliant models of the graft/ artery junction configuration. An ePTFE graft was then used to stiffen one of the models. These models were then investigated using two-dimensional video extensometry and one-dimensional laser Doppler anemometry to determine the junction deformations and fluid velocity profiles for the rigid and complaint graft anastomotic junctions. Junction strains were evaluated and generally found to be under 5% with a peak stain measured in the stiff graft model junction of 8.3% at 100 mmHg applied pressure. Hemodynamic results were found to yield up to 40% difference in fluid velocities for the stiff/compliant comparison but up to 80% for the proximal/distal end comparisons. Similar strain conditions were assumed for the proximal and distal models while significant differences were noted in their associated hemodynamic changes. In contrasting the fluid dynamics and wall mechanics for the proximal and distal anastomoses, it is evident from the results of this study, that junction hemodynamics are the more variable factor.

In this study, we present an adaptive anisotropic finite element method (FEM) and demonstrate how computational efficiency can be increased when applying the method to the simulation of blood flow in the cardiovascular system. We use the SUPG formulation for the transient 3D incompressible Navier-Stokes equations which are discretised by linear finite elements for both the pressure and the velocity field. Given the pulsatile nature of the flow in blood vessels we have pursued adaptivity based on the average flow over a cardiac cycle. Error indicators are derived to define an anisotropic mesh metric field. Mesh modification algorithms are used to anisotropically adapt the mesh according to the desired size field. We demonstrate the efficiency of the method by first applying it to pulsatile flow in a straight cylindrical vessel and then to a porcine aorta with a stenosis bypassed by a graft. We demonstrate that the use of an anisotropic adaptive FEM can result in an order of magnitude reduction in computing time with no loss of accuracy compared to analyses obtained with uniform meshes.

We have developed a high-frequency, high-resolution Doppler spectrum analyzer (DSPW) and compared its performance against an adapted clinical Medasonics spectrum analyzer (MSA) and a zero-crossing interval histogram (ZCIH) used previously by us to evaluate cardiovascular physiology in mice. The aortic velocity (means +/- SE: 92.7 +/- 2.5 versus 82.2 +/- 1.8 cm/s) and aortic acceleration (8194 +/- 319 versus 5178 +/- 191 cm/s2) determined by the DSPW were significantly higher compared to those by the MSA. Aortic ejection time was shorter (48.3 +/- 0.9 versus 64.6 +/- 1.8 ms) and the isovolumic relaxation was longer (17.6 +/- 0.6 versus 13.5 +/- 0.6 ms) when determined by the DSPW because it generates shorter temporal widths in the velocity spectra when compared to the MSA. These data indicate that the performance of the DSPW in evaluating cardiovascular physiology was better than that of the MSA. There were no significant differences between the aortic pulse wave velocity determined by using the ZCIH (391 +/- 16 cm/s) and the DSPW (394 +/- 20 cm/s). Besides monitoring cardiac function, we have used the DSPW for studying peripheral vascular physiology in normal, transgenic, and surgical models of mice. Several applications such as the detection of high stenotic jet velocities (> 4 m/s), vortex shedding frequencies (250 Hz), and subtle changes in wave shapes in peripheral vessels which could not obtained with clinical Doppler systems are now made possible with the DSPW.

Pulmonary hypertension affects nearly one-third of adults with sickle cell disease and is related to hemolysis. Although pulmonary pressures are not as high as in other forms of pulmonary hypertension, sickle cell patients poorly tolerate even moderate elevations of pulmonary pressures, because this complication predicts short survival. Tricuspid regurgitant jet velocity measured noninvasively by echocardiography is an adequate tool to screen for pulmonary hypertension. Because patients with pulmonary hypertension are older and often severely affected by other vaso-occlusive complications, optimizing their treatment with hydroxyurea or transfusions is important. Newer agents such as sildenafil and bosentan have demonstrated efficacy in other forms of pulmonary hypertension, and future clinical trials may prove them helpful in sickle cell patients.

We have developed and evaluated a high-frequency, real-time pulsed Doppler and physiological signal acquisition and analysis system specifically for use in mice. The system was designed to provide sampling rates up to 125 kilosamples/s (ksps) with software controlled data acquisition and analysis in real-time. Complex fast Fourier transforms are performed every 0.1 ms (or longer up to 10 ms) to provide 0.1-ms time resolution and using 64-1024 sample segments of the Doppler audio signals resulting in frequency resolution ranging from 122-1953 Hz. The system was evaluated by its response to frequency swept signals with slopes (accelerations) and magnitudes (velocities) comparable to actual blood velocity signals in mice. Signals up to a maximum frequency of 125 kHz and a maximum acceleration of 20 MHz/s were processed and displayed. This corresponds to a maximum velocity of 480 (960) cm/s and a maximum acceleration of 750 (1500) m/s2 when Doppler shifts are measured with a 20- (10-) MHz probe, thereby allowing us to measure high stenotic jet velocities. The directional transitions of the spectrogram across zero frequency and across Nyquist frequency (sampling rate/2) were smooth with no discernible artifacts. Signals with period as low as 2 ms were processed and displayed at sweep speed that is ten times that in clinical Doppler systems, so that measurements of small temporal events can be made with precision. Thus, the new system can measure higher blood velocities with higher spatial and temporal resolution than is possible using clinical Doppler systems adapted for use in mice.

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.

Rotary blood pumps offer a cost-effective way to assist the failing heart. Relative to their pulsatile cousins, they can consist of remarkably few moving parts, with attendant advantages in reliability. These advantages are realized in full only if the entire assist system is kept maximally simple. Control of the pump must therefore be based on a minimum number of measurement devices. This paper reviews the measurements that are made in the wide range of implantable rotary blood pump designs that are in development for ventricular assist. In a number of these, fluid-mechanical variables are estimated indirectly from measurements of motor speed and current or power. The introduction explains the goals of rotary blood pump control by comparison to the innate properties of the natural heart. Then motor and fluid-mechanical variables that may be transduced are discussed. Methods of indirect estimation of pressure drop and flow-rate are dealt with, followed by ways of detecting unusual states such as inflow obstruction. It is found that detection of these alone can be the basis of an adequate control strategy. Some groups have estimated variables pertaining to the heart that is being assisted, and there has also been work on monitoring the ongoing health of the assist system itself. The review concludes with a brief look at the wider measurement context for the intensive-care facility that proposes to use such devices to provide circulatory support.

Blood suspension fails to penetrate a capillary with radius R less than 50 microm even if the capillary is perfectly wettable. This invasion threshold is attributed to three red blood cells (RBCs) segregation mechanisms--corner deflection at the entrance, the intermediate deformation-induced radial migration and shear-induced diffusion within a packed slug at the meniscus. The shear-induced radial migration for deformable particles endows the blood cells with a higher velocity than the meniscus to form the concentrated slug behind the meniscus. This tightly packed slug has a higher resistance and arrests the flow. Rigid particles and rigidified blood cells result in wetting behavior similar to that seen for homogeneous liquids, with decreased RBC migration towards the capillary centerline and reduction of packing. Corner deflection with a radial drift velocity accelerates the radial migration for small capillaries. However, deformation-induced radial migration is the key mechanism responsible for penetration failure. This sequence of mechanisms is confirmed through videomicroscopy and scaling theories were applied to capture the dependence of the critical capillary radius as a function of RBC concentrations.

For a better insight in dialyzer efficiency with respect to local mass transport in a low flux dialyzer (Fresenius F6HPS), blood and dialysate flow distributions were visualized with computational fluid dynamic (CFD) simulations, which were validated with single photon emission computed tomography (SPECT) imaging. To visualize blood-side flow while avoiding transport through the fiber membrane, a bolus of 99m-Technetium labeled MAA (Macro Aggregated Albumin) was injected in the flow using an electronic valve. Water was used to simulate blood, but flow rate was adjusted according to laws of dynamic similarity to account for the viscosity difference (factor 2.75). For the visualization of dialysate flow, a bolus of 99m-Technetium labeled DMSA (Dimercaptosuccinic Acid) was injected, while pressurized air in the blood compartment avoided transmembrane flow. For each test series, 3D acquisitions were made on a two respectively three-headed SPECT camera. By evaluating the images at different time steps, dynamic 3D intensity plots were obtained, which were further used to derive local flow velocities. Additionally, three-dimensional CFD models were developed for simulating the overall blood and dialysate flow, respectively. In both models,the whole fiber compartment was defined as a porous medium with overall axial and radial permeability derived theoretically and from in vitro tests. With the imaging as well as with the computational technique, a homogeneous blood flow distribution was found, while vortices and fluid stagnation were observed in the dialyzer inlet manifold. The non-homogeneous dialysate distribution, as found with SPECT imaging, implies the occurrence of non-efficient sites with respect to mass transfer. The discrepancy between the dialysate results of both techniques indicated that the assumption of a constant fiber bundle permeability in the CFD model was too optimistic. In conclusion, medical imaging techniques like SPECT are very helpful to validate CFD models, which can be further applied for dialyzer design and optimization.

We have developed a sonomicrometer and continuous wavelength (CW) Doppler flowmeter for a multichannel telemetry system. These developments will enable us to measure ventricular dimension and coronary artery blood velocity, which are valuable parameters to characterize sudden cardiac death (SCD) in ambulatory animal models of ventricular arrhythmias. The design goals for the sensors were accuracy, low power consumption, small size and compatibility with each other. The circuits were designed successfully and tested simultaneously in vivo. The CW Doppler flowmeter draws 9 mA and the sonomicrometer draws 28 mA on a 5-V supply. The ability to measure heart dimension and blood velocity will add significantly to our understanding of the sequence of events leading up to spontaneous sudden cardiac death.

In our previous papers, we reported that factor IX (FIX), when activated by erythrocyte membranes, causes coagulation. We have identified and characterized the FIX-activating enzyme located in normal human erythrocyte membranes. In this paper, to examine physiological and pathological significances of procoagulant activity of erythrocytes, coagulation of blood obtained from different individuals was analyzed by means of a rheological technique. In more than 65% of subjects including normals and patients, the initiation of coagulation seemed to be governed by erythrocytes. Coagulation of whole blood and platelet-free plasma supplemented with erythrocytes had a tendency to occur rapidly in the elderly. It was suggested that the concentration of FIX-activating enzyme on erythrocyte membranes for aged donors was somewhat higher than that for young ages. Propagation reactions on erythrocyte membranes (i.e. factor X activation leading to thrombin generation after FIX activation) was slower than that on platelet membranes. Moreover, the propagation reaction on erythrocyte membranes was greatly dependent on individuals, whereas that on platelet membranes was not so much. Our study demonstrates that the activation of FIX by erythrocytes and subsequent propagation reaction on platelet membranes may be important for initiating and controlling blood coagulation reactions.

Coronary stents are supportive wire meshes that keep narrow coronary arteries patent, reducing the risk of restenosis. Despite the common use of coronary stents, approximately 20-35% of them fail due to restenosis. Flow phenomena adjacent to the stent may contribute to restenosis. Three-dimensional computational fluid dynamics (CFD) and reconstruction based on biplane cine angiography were used to assess coronary geometry and volumetric blood flows. A patient-specific left anterior descending (LAD) artery was reconstructed from single-plane x-ray imaging. With corresponding electrocardiographic signals, images from the same time phase were selected from the angiograms for dynamic three-dimensional reconstruction. The resultant three-dimensional LAD artery at end-diastole was adopted for detailed analysis. Both the geometries and flow fields, based on a computational model from CAE software (ANSYS and CATIA) and full three-dimensional Navier-Stroke equations in the CFD-ACE+ software, respectively, changed dramatically after stent placement. Flow fields showed a complex three-dimensional spiral motion due to arterial tortuosity. The corresponding wall shear stresses, pressure gradient, and flow field all varied significantly after stent placement. Combined angiography and CFD techniques allow more detailed investigation of flow patterns in various segments. The implanted stent(s) may be quantitatively studied from the proposed hemodynamic modeling approach.

Vascular infusions of 15-microm-diameter microspheres are used to study pulmonary blood flow distribution. The sites of microsphere lodging and their effects on microvascular perfusion are debated but unknown. Using intravital microscopy of the subpleural surface of rat lungs, we directly observed deposition of fluorescent microspheres. In a pump-perfused lung model, approximately 0.5 million microspheres were infused over 30 s into the pulmonary artery of seven rats. Microsphere lodging was analyzed for the location in the microvasculature and the effect on local flow after lodging. On average, we observed 3.2 microspheres per 160 alveolar facets. The microspheres always entered the arterioles as singlets and lodged at the inlets to capillaries, either in alveolar corner vessels or small arterioles. In all cases, blood flow continued either around the microspheres or into the capillaries via adjacent pathways. We conclude that 15-microm-diameter microspheres, in doses in excess of those used in typical studies, have no significant impact on pulmonary capillary blood flow distribution.

Blood viscosity changes with many pathologic conditions, but its importance has not been fully investigated because the current methods of measurement are poorly suited for clinical applications. The use of viscosity-sensitive fluorescent molecular rotors to determine fluid viscosity in a nonmechanical manner has been investigated recently, but it is unknown how the precision of the fluorescence-based method compares to established mechanical viscometry. Human blood plasma viscosity was modulated with high-viscosity plasma expanders, dextran, pentastarch, and hetastarch. The samples were divided into a calibration and a test set. The relationship between fluorescence emission and viscosity was established using the calibration set. Viscosity of the test set was determined by fluorescence and by cone-and-plate viscometer, and the precision of both methods compared. Molecular rotor fluorescence intensity showed a power law relationship with solution viscosity. Mechanical measurements deviated from the theoretical viscosity value by less than 7.6%, while fluorescence-based measurements deviated by less than 6%. The average coefficient of variation was 6.9% (mechanical measurement) and 3.4% to 3.8% (fluorescence-based measurement, depending on the molecular rotor used). Fluorescence-based viscometry exhibits comparable precision to mechanical viscometry. Fluorescence viscometry does not apply shear and is therefore more practical for biofluids which have apparent non-Newtonian properties. In addition, fluorescence instrumentation makes very fast serial measurements possible, thus promising new areas of application in laboratory and clinical settings.

Background: The aim in this study is to evaluate a new method of measuring total coronary blood flow (TCBF) in (1) an in vitro model and in (2) an animal model by the lithium dilution method., Methods: (1) Ringer's solution was circulated in a closed circuit with the main flow as a systemic circulation, and the side flow as a coronary circulation by a roller pump. Two peaks originating from the main and side flow were recorded by the lithium dilution method. The flow was calculated using the Fick principle based on the ratio of the areas under the curve. The validity of this method was evaluated by Bland Altman analysis. (2) Four beagles were anesthetized and subjected to insertion of two pulmonary artery catheters. The position of the catheters was confirmed as being in the pulmonary artery and in the right atrium. Lithium chloride solution was injected into the pulmonary artery and the change in lithium concentration at the right atrium was recorded. TCBF was estimated by the method used in the in vitro study., Results: (1) The calculated flow correlated well with the actual flow (r2 = 0.86). (2) The estimated TCBF at baseline, with low-dose nitroglycerin, and with high-dose nitroglycerin was 206 +/- 43.0 mL/min, 304 +/- 50.3 mL/min, and 348 +/- 50.1 mL/min, respectively (mean +/- SE). TCBF was significantly increased by nitroglycerin infusion., Conclusion: A new method of measuring TCBF using the lithium dilution method was reliable and useful both in vitro and in an animal model. This may be clinically useful method for measuring TCBF.

In this paper we present a method for simulating bleeding in a virtual reality hysteroscopic simulator for surgical training. The simulated bleeding is required to be visually appealing while at the same time instantaneously responsive to any feedback that the surgeon may be conducing to the virtual environment. In order to meet these real-time requirements, we have based the simulation on graphical fluid solvers. These solvers primarily work best over a 2D domain. For correct visualization in the hysteroscopic simulator, it is, however, necessary to perform the simulation fully in 3D. Therefore in this paper we also present the design modifications for 3D graphical fluid solving and show how to use parallelization to maintain real-time behavior. We also discuss how the incorporation of massless particles into the simulation can improve the visual quality of the results by limiting numerical dissipation effects.

The current study was designed to determine the effects of a dietary astaxanthin (ASX-O) on vascular reactivity in spontaneously hypertensive rats (SHR), in order to verify its antihypertensive action mechanism. We evaluated contractions induced by phenylephrine (Phe), angiotensin II (Ang II) and the xanthine/xanthine oxidase (Xan/XOD) system, and relaxations induced by sodium nitroprusside (SNP) as well as endothelium-dependent relaxations mediated by acetylcholine (ACh) in thoracic aorta of the SHR, with and without ASX-O intervention. We also investigated the effects of ASX-O on blood rheology using a microchannel array system. In this study, ASX-O showed a significant modulatory effect on nitric oxide (NO)-induced vasorelaxation by the NO-donor SNP (p<0.05). However, it did not show significant effects in restoring the impaired endothelium-dependent relaxation to ACh in the SHR. On the other hand, the constrictive effects by Phe, Ang II and Xan/XOD were ameliorated by ASX-O (p<0.05). ASX-O also demonstrated significant hemorheological effect by decreasing the microchannel transit time of whole blood. In conclusion, the results suggest that ASX-O may act in modulating the blood fluidity in hypertension, and that the antihypertensive effects of ASX-O may be exerted through mechanisms including normalization of the sensitivity of the adrenoceptor sympathetic pathway, particularly [alpha]-adrenoceptors, and by restoration of the vascular tone through attenuation of the Ang II- and reactive oxygen species (ROS)-induced vasoconstriction.