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Objective: Blood flow is considered one of the important parameters that contribute to venous thrombosis. We quantitatively test the relationship between initiation of coagulation and shear rate and suggest a biophysical mechanism to understand this relationship., Methods and Results: Flowing human blood and plasma were exposed to cylindrical surfaces patterned with patches of tissue factor (TF) by using microfluidics. Initiation of coagulation of normal pooled plasma depended on shear rate, not volumetric flow rate or flow velocity, and coagulation initiated only at shear rates below a critical value. Initiation of coagulation of platelet-rich plasma and whole blood showed similar behavior. At constant shear rate, coagulation of plasma also showed a threshold response to the size of a patch of TF, consistent with our previous work in the absence of flow., Conclusions: Initiation of coagulation of flowing blood displays a threshold response to shear rate and to the size of a surface patch of TF. Combined with the results of others, these results set the range of shear rates that limit initiation of coagulation by small surface areas of TF and by shear activation of platelets. This range fits the relatively narrow range of physiological shear rates described by Murray's law.

Little is understood about endothelial cell (EC) responses to high flow, which mediate adaptive outward remodeling as well as cerebral aneurysm development. Opposite EC behaviors have been reported in vivo including cell loss during aneurysm initiation and cell proliferation during adaptive outward remodeling. This study aims at elucidating the EC growth response to elevated wall shear stress (WSS) and determining if nitric oxide (NO) is involved. A confluent EC monolayer was subjected to steady-state, laminar flow with WSS ranging from 15 to 100 dyn/cm(2) for 24 and 48 h. Cells oriented to the direction of the flow with a time course that varied with WSS. At 48 h, all cells were aligned with the flow. EC proliferation was examined using bromodeoxyuridine (BrdU) incorporation. The percentage of proliferating ECs rose linearly from 15 to 50 dyn/cm(2) to more than sixfold at 50-100 dyn/cm(2) compared with the accepted physiological baseline of 15-20 dyn/cm(2). In addition, terminal deoxynucleotidyl transferase dUTP-mediated nick-end labeling (TUNEL) staining revealed that apoptosis decreased with increasing WSS. These results demonstrate that high WSS stimulates EC proliferation and suppresses apoptosis. Furthermore, immunostaining revealed increased endothelial nitric oxide synthase (eNOS) production with increasing WSS. NOS inhibition with N(omega)-nitro-l-arginine methyl ester (l-NAME) drastically reduced the WSS-stimulated proliferation, indicating a critical role of NO production in the stimulation of EC proliferation by high WSS.

Improved methods are needed to identify patients at risk for thrombotic or bleeding events. Free oscillation rheometry (FOR) is a technique that offers information on coagulation, based on contributions of all blood components, by measurement of clotting time and changes in clot elasticity. This is the first study that evaluates FOR parameters in subjects likely to represent hypercoagulability (pregnant women) and hypocoagulability (thrombocytopenic patients). Clotting time and blood clot elasticity were measured by FOR in blood samples obtained from women in different pregnancy trimesters (n = 58), in thrombocytopenic patients before and after a platelet transfusion (n = 20) and in healthy blood donors (n = 60). The clotting time was shorter and the clot elasticity higher in pregnant women compared to the non-pregnant female blood donors. The elasticity was higher in late pregnancy compared to early pregnancy. Compared to the blood donors, the thrombocytopenic patients had lower elasticity, which was increased by a platelet transfusion, but there was no difference in clotting time. The results suggest that FOR can provide new information on the haemostatic status of patients at risk of thrombotic or bleeding events as well as information on the haemostatic effect of a platelet transfusion.

Mechanical forces are known to affect the biomechanical properties of native and engineered cardiovascular tissue. In particular, shear stress that results from the relative motion of heart valve leaflets with respect to the blood flow is one important component of their mechanical environment in vivo. Although different types of bioreactors have been designed to subject cells to shear stress, devices to expose biological tissue are few. In an effort to address this issue, the aim of this study was to design an ex vivo tissue culture system to characterize the biological response of heart valve leaflets subjected to a well-defined steady or time-varying shear stress environment. The novel apparatus was designed based on a cone-and-plate viscometer. The device characteristics were defined to limit the secondary flow effects inherent to this particular geometry. The determination of the operating conditions producing the desired shear stress profile was streamlined using a computational fluid dynamic (CFD) model validated with laser Doppler velocimetry. The novel ex vivo tissue culture system was validated in terms of its capability to reproduce a desired cone rotation and to maintain sterile conditions. The CFD results demonstrated that a cone angle of 0.5 deg, a cone radius of 40 mm, and a gap of 0.2 mm between the cone apex and the plate could limit radial secondary flow effects. The novel cone-and-plate permits to expose nine tissue specimens to an identical shear stress waveform. The whole setup is capable of accommodating four cone-and-plate systems, thus concomitantly subjecting 36 tissue samples to desired shear stress condition. The innovative design enables the tissue specimens to be flush mounted in the plate in order to limit flow perturbations caused by the tissue thickness. The device is capable of producing shear stress rates of up to 650 dyn cm(-2) s(-1) (i.e., maximum shear stress rate experienced by the ventricular surface of an aortic valve leaflet) and was shown to maintain tissue under sterile conditions for 120 h. The novel ex vivo tissue culture system constitutes a valuable tool toward elucidating heart valve mechanobiology. Ultimately, this knowledge will permit the production of functional tissue engineered heart valves, and a better understanding of heart valve biology and disease progression.

The velocity fields within the impeller passages of three different impellers of the Kyoto-NTN bio-centrifugal ventricular assist device are measured using laser Doppler velocimetry in this study. The 16 forward-swept-blade impeller has better performance than the 16 straight-blade and 8 backward-swept-blade impellers in terms of smooth flow pattern, and has less high-shear-stress regions in the passages. The flow distributions are found to be similar with those measured by Yu et al. Through-flow characteristics are found in the impeller when the passages open to the biggest volute space. The flow fields in the blade channels of the impeller were found to be axis symmetrical due to the double volute design with the objective of minimizing the imbalance of the radial thrust when the impeller is magnetically suspended. In addition, the high-intensity vortex which was detected by Yu et al. at the discharge channel of the pump is effectively reduced when the end of the splitter plate is modified by increasing the taper ratio from 4 to 20. The new design would reduce the hemolysis of blood due to the high shear rate of the vortex.

Objective: Intermittent pneumatic compression (IPC) systems are used for prophylaxis of venous thromboembolism. Both legs are wrapped with inflatable sleeves connected to a pneumatic controller to allow compression of the legs causing expulsion of venous blood. Venous refill between inflation periods causes leg expansion, which can be tracked by measuring pressure changes in the sleeve. The aim of our study, which utilized the SCD RESPONSE compression system in conjunction with an independent pressure transducer, was to investigate whether factors such as temperature changes within the sleeves during inflation and deflation affect the measured venous refill time (VRT)., Methods: Transducers were used to measure air pressure in the middle chamber of the sleeve. A thermocouple was also inserted into the bladder to measure temperature changes. Inflation, deflation and refill measurements were made with the sleeves around model systems (static, rigid plastic pipes or compliant paper rolls, and dynamic, latex tubes inserted between a rigid pipe and the sleeve to simulate veins) and on 10 subjects in semi-recumbent, supine and sitting positions., Results: In all the experiments the maximum temperature change was 0.023 degrees C. With the static model systems, the pressure in the venous refill measuring bladder fell from the inflation pressure of 40 - 50 mmHg to 9 +/- 1 mmHg, but then rose by 2.1 +/- 0.2 mmHg (rigid pipes) and 1.4 +/- 0.2 mmHg (paper rolls). These pressure changes were associated with reported 'filling times' of 21 - 24 s (rigid pipes) and 22 - 29 s (paper rolls). In experiments on dynamic filling of the latex tube, there was a strong linear relationship between the filling time indicated by the SCD system and the time to empty the filling reservoir. In 170 measurements on human subjects, there were only three VRTs less than 30 s and 36 less than 35 s. VRT increased in all subjects when going from supine (34.6 +/- 1.8 s) to semi-recumbent (38.9 +/- 1.9 s) to sitting (42.6 +/- 0.9 s) positions., Discussion: In all cases, temperature changes during the refill phase were too small to result in significant pressure changes that would affect VRT. The pressure increases observed with the static models after deflation appeared to be due to viscoelastic relaxation. Viscoelastic responses were present in human subjects, but the effect on VRT was negligible. This indicates that the increased VRT observed in humans is due to blood return. Body position affected VRTs, indicating the system's ability to detect changes in filling times and venous blood volume.

Perioperative monitoring of blood coagulation is critical to better understand causes of hemorrhage, to guide hemostatic therapies, and to predict the risk of bleeding during the consecutive anesthetic or surgical procedures. Point-of-care (POC) coagulation monitoring devices assessing the viscoelastic properties of whole blood, i.e., thrombelastography, rotation thrombelastometry, and Sonoclot analysis, may overcome several limitations of routine coagulation tests in the perioperative setting. The advantage of these techniques is that they have the potential to measure the clotting process, starting with fibrin formation and continue through to clot retraction and fibrinolysis at the bedside, with minimal delays. Furthermore, the coagulation status of patients is assessed in whole blood, allowing the plasmatic coagulation system to interact with platelets and red cells, and thereby providing useful additional information on platelet function. Viscoelastic POC coagulation devices are increasingly being used in clinical practice, especially in the management of patients undergoing cardiac and liver surgery. Furthermore, they provide useful information in a large variety of clinical scenarios, e.g., massive hemorrhage, assessment of hypo- and hypercoagulable states, guiding pro- and anticoagulant therapies, and in diagnosing of a surgical bleeding. A surgical etiology of bleeding has to be considered when viscoelastic test results are normal. In summary, viscoelastic POC coagulation devices may help identify the cause of bleeding and guide pro- and anticoagulant therapies. To ensure optimal accuracy and performance, standardized procedures for blood sampling and handling, strict quality controls and trained personnel are required.

The viscosity of blood obtained by using a rotational viscometer decreases with the time elapsed from the beginning of measurement until it reaches a constant value determined by the magnitude of shear rate. It is not possible to obtain an initial value of viscosity at time t = 0 that is considered to exhibit an intrinsic property of the fluid by this method. Therefore, we devised a new method by which one can obtain the viscosity of various fluids that are not affected by both the time elapsed from the beginning of measurement and the magnitude of shear rate by considering the balance of the forces acting on a solid spherical particle freely falling in a quiescent viscous fluid. By using the new method, we studied the rheologic behavior of corn syrups, carboxy-methyl cellulose, and human blood; and compared the results with those obtained with a cone-and-plate viscometer. It was found that in the case of corn syrups and washed red cell suspensions in which no red cell aggregate (rouleau) was formed, the viscosity obtained with the two different methods were almost the same. In contrast to this, in the case of the whole blood in which massive aggregates were formed, the viscosity obtained with a falling-ball viscometer was much larger than that obtained with a cone-plate viscometer.

I present an historical overview beginning with Prof. Harry L. Goldsmith, my first summer research supervisor in 1963 in microrheology, evolving years later to introduction into my laboratories at McGill University of the coaxial cylinder couette flow device for dynamic, real-time measurements of platelet aggregation in platelet suspensions sheared up to 8000/s, analyzed with a flow cytometer, and finally to a technology transfer of this rheological approach toward the marketplace. I and collaborators observed the shear-dependent roles of different adhesive receptors in mediating human platelet aggregation, and the importance of shear in evaluating efficacy of antiplatelet drugs, in contrast to studies with a classical aggregometer. I outline the well-published rationale for using flow devices, such as the coaxial cylinder couette, to assist clinicians and health managers assess the drug and clinical outcome efficacy of antithrombotic drugs in cardiovascular diseases, as well as their future applications.

Computational fluid dynamics (CFD) methods based on in vivo three-dimensional vessel reconstructions have recently been shown to provide prognostically relevant hemodynamic data. However, the geometry reconstruction and the assessment of clinically relevant hemodynamic parameters may depend on the used imaging modality. This study compares geometric reconstruction and calculated wall shear stress (WSS) values based on magnetic resonance imaging (MRI) and computed tomography (CT). Both imaging methods were applied to a same 2.5-fold upscale silicon model of the left coronary artery (LCA) main bifurcation. The original model is an optically digitized post mortem vessel cast. This digitized geometry is considered as a "gold standard" or original geometry for the MRI versus CT comparative study. The use of the upscale model allowed generating a high resolution CT raw data set with voxel size of 0.156 x 0.156 x 0.36 mm(3) and a high resolution MRI data set with an equivalent voxel size of 0.196 x 0.196 x 0.196 mm(3) for corresponding in vivo conditions. MRI based reconstruction achieved a mean Hausdorff surface distance of 0.1 mm to the original geometry. This is 2.5 times better than CT based reconstruction with mean Hausdorff surface distance of 0.252 mm. A comparison of the calculated mean WSS shows good correlation (r = 0.97) and good agreement among the three modalities with a WSS of 0.65 Pa in the original model, of 0.68 Pa in the CT based model and of 0.67 Pa in the MRI based model.

We report studies of the coagulation of samples of whole human blood by oscillatory shear techniques, including Fourier Transform Mechanical Spectroscopy (FTMS). These techniques are used herein to identify the Gel Point of coagulating blood in terms of the Chambon-Winter Gel Point criterion which provides a rheometrical basis for detecting the establishment of an incipient clot. A comparison of the results of FTMS with those obtained from measurements involving a Thromboelastograph (TEG) and a Free Oscillation Rheometer (FOR) indicate that the latter techniques are not capable of detecting the incipient clot, whose establishment occurs several minutes prior to TEG or FOR-based assessments of clot formation time. The results of the present study suggest that FTMS is a useful tool in blood clotting research, being capable of providing a global coagulation profile in addition to detecting the instant of incipient clot formation.

The absence of a simple and clinically practical method to determine whole blood viscosity can partly justify why the medical community has been slow in realizing the significance of whole blood viscosity. For this reason, the availability of a technique able to evaluate blood viscosity in a rapid and direct manner is welcome. To evaluate the feasibility in hemorheological laboratory of a new torsional oscillation viscometer, it was compared with a conventional cone-plate system. The viscosity comparison has been related to hematocrit value both on whole blood and suspended blood in a saline solution. The results showed a good repeatability and reproducibility of the new equipment, with a best-fitting data of the hematocrit 0-100% range characterized by coefficient of determinations, r2>0.95. Furthermore, a comparison of whole blood viscosity as measured by the two instruments was done on blood samples collected from hospitalized patients. Reasonable agreement for the viscosity values was found between the two methods with linear determination coefficients between the two measurement methods comprised between r2=0.7329 and 0.9263, depending on shear stress phase and the corresponding shear rate.

A new improved flow system was developed to study the influence of blood flow pulsatility on platelet adhesion on adhesive proteins and bio-medical materials. The pulsatility was introduced by changing the shear rate every 15 s in blood that was aspirated through a perfusion chamber by a syringe pump. The advantage of this new system is that it avoids system related platelet activation. At steady low shear rate (300/s) after 5 min a collagen type III surface was covered for 24.2+/-3.8% with platelets. At steady high shear rate (1300/s) platelet coverage to collagen was 48.8+/-6.8%. When pulsatility was introduced by changing the shear rate was every 15 s form 300/s to 1300/s and vice-versa, platelet coverage after 5 min was increased to 60.4+/-4.0% (p<0.001). After 5 min perfusion samples were taken from the perfusate and the extent of platelet activation was measured. The significant difference in surface expression of P-selectin on platelets is only seen when comparing pulse flow with control (no flow). We concluded that a significant increase in platelet activation during blood pulsatile flow compared with steady flow, which results in an increased platelet adhesion to collagen.

A quantitative flow measurement method that utilizes a sequence of photoacoustic images is described. The method is based on the use of gold nanorods as a contrast agent for photoacoustic imaging. The peak optical absorption wavelength of a gold nanorod depends on its aspect ratio, which can be altered by laser irradiation (we establish a wash-in flow estimation method of this process). The concentration of nanorods with a particular aspect ratio inside a region of interest is affected by both laser-induced shape changes and replenishment of nanorods at a rate determined by the flow velocity. In this study, the concentration is monitored using a custom-designed, high-frame-rate photoacoustic imaging system. This imaging system consists of fiber bundles for wide area laser irradiation, a laser ultrasonic transducer array, and an ultrasound front-end subsystem that allows acoustic data to be acquired simultaneously from 64 transducer elements. Currently, the frame rate of this system is limited by the pulse-repetition frequency of the laser (i.e., 15 Hz). With this system, experimental results from a chicken breast tissue show that flow velocities from 0.125 to 2 mms can be measured with an average error of 31.3%.

This article presents numerical investigations of the effect of radial gap and volute tongue position on the circumferential pressure distribution and the magnitude of resulting imbalanced radial force. A series of volute models was designed using the constant mean velocity method. The results indicate that a radial clearance of 10% is a good practical value that gives a relatively high head across the pump for a small radial force. The results show that the tongue position at 30 degrees gives the lowest radial force and pressure head. The tongue position at 15 degrees appears to give the best compromise results producing a generated head only 5% less than the maximum value while the radial force is about 22% less than the maximum force.

In this study, mechanical trauma to red blood cells was evaluated by conventional hemolysis test and a newly developed cyclically reversing shear flow generator. The fresh porcine blood obtained from a local slaughterhouse was subjected to the conventional hemolysis test using a commercial centrifugal blood pump for the duration of 8 h. The measurements consisted of (i) plasma-free hemoglobin based on the standard optical measurement and (ii) the deformability of red blood cells (RBCs) using a cyclically reversing shear flow generator and microscope image acquisition system. The deformability of RBCs was expressed by the L/W value where L and W were the longer and shorter axes of the elongated RBCs' images. Although the plasma-free hemoglobin level increased with the pumping duration, the L/W remained unchanged for the duration of 8 h of pumping to indicate no alteration in the deformability. It was speculated that (i) although RBCs might have been circulated for so many times through the test pump, after each exposure to mechanical stress, RBCs might have recovered, and net effect due to shear stress-exposure time might have been small; and (ii) RBCs' deformability might be maintained near normal until sudden burst or membrane rupture, or the hemoglobin might have continuously leaked through the pores of the thinned membrane created by the mechanical stress. The deformability testing under a fluctuating shear flow could be a new method to quantify subhemolytic mechanical damage that has been accumulated in the RBCs' membrane and that may not be assessed by the conventional hemolysis test.

A noninvasive diagnostic device was developed to assess the vascular origin and severity of penile dysfunction. It was designed and studied using both a mathematical model of penile hemodynamics and preliminary experiments on healthy young volunteers. The device is based on the application of an external pressure (or vacuum) perturbation to the penis following the induction of erection. The rate of volume change while the penis returns to its natural condition is measured using a noninvasive system that includes a volume measurement mechanism that has very low friction, thereby not affecting the measured system. The rate of volume change (net flow) is obtained and analyzed. Simulations using a mathematical model show that the device is capable of differentiating between arterial insufficiency and venous leak and indicate the severity of each. In preliminary measurements on young healthy volunteers, the feasibility of the measurement has been demonstrated. More studies are required to confirm the diagnostic value of the measurements.

Biotelemetry provides high-quality data in awake, free-ranging animals without the effects of anesthesia and surgery. Although many biological parameters can be measured using biotelemetry, simultaneous telemetric measurements of pressure and flow have not been available. The objective of this study was to evaluate simultaneous measurements of blood flow, pressure, ECG, and temperature in a fully implantable system. This novel system allows the measurement of up to four channels of blood flow, up to three channels of pressure, and a single channel each of ECG and temperature. The system includes a bidirectional radio-frequency link that allows the implant to send data and accept commands to perform various tasks. The system is controlled by a base station decoder/controller that decodes the data stream sent by the implant into analog signals. The system also converts the data into a digital data stream that can be sent via ethernet to a remote computer for storage and/or analysis. The system was chronically implanted in swine and alligators for up to 5 wk. Both bench and in vivo animal tests were performed to evaluate system performance. Results show that this biotelemetry system is capable of long-term accurate monitoring of simultaneous blood flow and pressure. The system allows, within the room, recordings, since the implant transmission range is between 6 and 10 m, and, with a relay, backpack transmission distance of up to 500 m can be achieved. This system will have significant utility in chronic models of cardiovascular physiology and pathology.

Microcirculation is the generic name of vessels with internal diameter less than 100 microm of the circulatory system, whose main functions are tissue nutrition and oxygen supply. In microcirculatory studies, it is important to know the amount of oxyhemoglobin present in the blood and how fast it is moving. The present work describes improvements introduced in a classical hardware-based instrument that has usually been used to monitor blood flow velocity in the microcirculation of small animals. It consists of a virtual instrument that can be easily incorporated into existing hardware-based systems, contributing to reduce operator related biases and allowing digital processing and storage. The design and calibration of the modified instrument are described as well as in vitro and in vivo results obtained with electrical models and small animals, respectively. Results obtained in in vivo studies showed that this new system is able to detect a small reduction in blood flow velocity comparing arteries and arterioles (p <0.002) and a further reduction in capillaries (p<0.0001). A significant increase in velocity comparing capillaries and venules (p <0.001) and venules and veins (p <0.001) was also observed. These results are in close agreement with biophysical principles. Moreover, the improvements introduced in the device allowed us to clearly observe changes in blood flow introduced by a pharmacological intervention, suggesting that the system has enough temporal resolution to track these microcirculatory events. These results were also in close conformity to physiology, confirming the high scientific potential of the modified system and indicating that this instrument can also be useful for pharmacological evaluations.

The deformability of erythrocytes primarily depends on the composition of the membrane and cytoplasm, which consist of hemoglobin and other constituents. Current techniques that measure erythrocyte deformability often require labor-intensive and time-consuming measurement processes. This article describes a newly developed microfluidic ektacytometer (RheoScan-D) that adopts advanced microfluidic rheometry and conventional laser-diffraction technique to determine the deformability of erythrocytes. Experiments are carried out to measure changes in deformability by treating erythrocytes in chemical agents with various concentrations (0, 0.3, 0.5 and 1.0 mM) of hydrogen peroxide, glutaraldehyde and diamide, and also by incubating erythrocytes at 49 degrees C for various time intervals (0, 5, 10 and 30 min), which affect the deformability through interaction with various constituents of erythrocytes. The measured Elongation Index (EI) of normal erythrocytes, a parameter directly related to erythrocyte deformability, at various shear stresses is in excellent agreement with those measured by a conventional ektacytometer (LORCA). The present technique is sensitive in detecting changes as produced by various chemical agents and high temperature. Alterations produced by hydrogen peroxide are the minimum and the maximums are produced by diamide treatment.

Liposomes are phospholipid vesicles that can serve as carriers of biologically active agents in vitro and in vivo. Here, we describe the movement of liposomes suspended with blood flowing in capillaries. Liposomes were coated with a polymer to extend their lifespan in rat mesenteric blood vessels and detected by fluorescent staining. Liposome activity was observed by intravital microscopy using a high-speed camera system at 5 and 60 min after liposome administration. Liposome velocity was determined using two-dimensional cross-correlation, and blood flow was measured by high-resolution PIV (particle image velocimetry). The results showed that the motion of polymer-coated liposome followed the phase averaged velocity distribution of heartbeats while flowing with red blood cells in microvessels. Liposome particles tend to move toward the near blood vessel wall in the low velocity of blood flow.

The deformability of erythrocytes is of great importance for oxygen delivery in the microcirculation [Lipowsky, H.H., 2005. Microvascular rheology and hemodynamics. Microcirculation 12, 5-15]. Aging of erythrocytes is associated with a reduction in deformability and also in size. The present work describes an automated cell analyzer which utilizes a glass microchannel and advanced image processing software. Erythrocytes suspended in a high viscosity medium are filmed flowing through the microchannel. Under these conditions, the cells assume different orientations and undergo varying deformations according to their location in the velocity profile. The cell analyzer enables the measurement of individual erythrocyte velocity, deformability and volume at varying depths within the microchannel. The volume of the cells is calculated based on the experimental data and a fluid mechanics model. The results obtained show that, on average, the deformability of the cells increases with increase in their size. Additionally, the behavior of RBCs in a microchannel is investigated, showing promising diagnostic possibilities.

A confocal microparticle image velocimetry (micro-PIV) system was used to obtain detailed information on the velocity profiles for the flow of pure water (PW) and in vitro blood (haematocrit up to 17%) in a 100-microm-square microchannel. All the measurements were made in the middle plane of the microchannel at a constant flow rate and low Reynolds number (Re=0.025). The averaged ensemble velocity profiles were found to be markedly parabolic for all the working fluids studied. When comparing the instantaneous velocity profiles of the three fluids, our results indicated that the profile shape depended on the haematocrit. Our confocal micro-PIV measurements demonstrate that the root mean square (RMS) values increase with the haematocrit implying that it is important to consider the information provided by the instantaneous velocity fields, even at low Re. The present study also examines the potential effect of the RBCs on the accuracy of the instantaneous velocity measurements.

The present paper addresses the numerical optimization of geometrical parameters of non-Newtonian micro-scale viscous pumps for biomedical devices. The objective is to maximize the mass flow rate per unit of shaft power consumed by the rotor when an external pressure load is applied along the channel that houses the rotor. Two geometric parameters are considered in the optimization process: (i) the height of the channel that houses the rotor (H) and (ii), the eccentricity (epsilon) of the rotor. Three different micro-scale viscous pump configurations were tested: a straight-housed pump (I-shaped housing) and two curved housed pumps (L- and U-shaped housings). The stress-strain constitutive law is modeled by a power-law relation. The results show that the geometric optimization of micro-scale viscous pumps is critical since the mass flow rate propelled by the rotor is highly dependent on epsilon and H. Numerical simulations indicate that mass flow rate is maximized when epsilon approximately 0, namely when the rotor is placed at a distance of 0.05 radii from the lower wall. The results also show that micro-scale viscous pumps with curved housing provide higher mass flow rate per unit of shaft power consumed when compared with straight-housed pumps. The results are presented in terms optimized dimensions of all three configurations (i.e., H(opt) and epsilon(opt)) and for values of the power-law index varying between 0.5 (shear thinning fluids) and 1.5 (shear-thickening fluids).

We have been developing a pneumatic ventricular assist device (PVAD) system consisting of a diaphragm-type blood pump. The objective of the present study was to evaluate the flow pattern inside the PVAD, which may greatly affect thrombus formation, with respect to the inflow valve-mount orientation. To analyze the change of flow behavior caused by the orifice direction (OD) of the valve, the flow pattern in this pump was visualized. Particle image velocimetry was used as a measurement technique to visualize the flow dynamics. A monoleaflet mechanical valve was mounted in the inlet and outlet ports of the PVAD, which was connected to a mock circulatory loop tester. The OD of the inlet valve was set at six different angles (OD = 0 degrees, 45 degrees, 90 degrees, 135 degrees, 180 degrees, and 270 degrees, where the OD opening toward the diaphragm was defined as 0 degrees ) and the pump rate was fixed at 80 bpm to create a 5.0 l/min flow rate. The main circular flow in the blood pump was affected by the OD of the inlet valve. The observed regional flow velocity was relatively low in the area between the inlet and outlet port roots, and was lowest at an OD of 90 degrees. In contrast, the regional flow velocity in this area was highest at an OD of 135 degrees. The OD is an important factor in optimizing the flow condition in our PVAD in terms of preventing flow stagnation, and the best flow behavior was realized at an OD of 135 degrees.

Sepsis in different states of severity (sepsis, severe sepsis, septic shock and adult respiratory distress syndrome (ARDS)) is associated with microcirculatory blood flow abnormalities leading to decreased red blood cell's (RBC's) deformability, impaired oxygen delivery to tissues and organs failure. The main goal of the present study, was to first determine the values of RBC's deformability, in the course of patients treated in an Intensive Care Unit (ICU) for basically sepsis and then deteriorated states and secondly to establish the prognostic efficiency of the test. For this purpose a filtration method and the hemorheometer, was used to determine experimentally the RBC's deformability, by measuring the RBC's Index of Rigidity (IR). Our results indicated that the IR was significantly increased in all patient groups and it was found to be approximately 51% higher in patients with sepsis, 229% in patients with severe sepsis, 1285% in patients with septic shock and 923% in patients with ARDS than in the healthy donors. The relationships between IR and Simplified Acute Physiology Score II (SAPS) and IR and Projected Mortality (PM) were found to be IR = 2.0237(SAPS) - 58.807 (r=0.731) and IR = 1.0671(PM) - 5.9829 (r=0.726) respectively. Our findings imply a significant impairment of the membrane's deformability possibly due to changes in its structure. It seems that the RBC's deformability is a useful mechanical parameter to estimate the prognosis and monitor patients suffering from different severity levels of sepsis.

A noncontact type centrifugal pump without any complicated control or sensing modules has been developed as a long-term implantable artificial heart. Centrifugal pumps with impellers levitated by original hydrodynamic bearings were designed and have been modified through numerical analyses and in vitro tests. The hemolysis level was reduced by changing the pressure distribution around the impeller and subsequently expanding the bearing gap. Thrombus formation in the bearing was examined with in vitro thrombogenesis tests and was reduced by changing the groove shapes to increase the bearing-gap flow to 3% of the external flow. Unnecessary vortices around the vanes were also eliminated by changing the number of vanes from four to six.

Information about muscular tissue flow is important for diagnosing, treating and monitoring patients with tissue ischemia. For this purpose an objective method which is reproducible and continuous is needed. In co-operation with the company Unisense A/S, we have developed a sensor for instantaneous and continuous monitoring of muscle tissue flow in vivo. The method is based on a flexible microsensor which emits and measures minute amounts of inert tracer gases. The objective was to evaluate the capability of the microsensor to measure varying degrees of tissue flow changes and compare these measurements with the 133Xenon Washout Technique for measuring local perfusion rates in skeletal muscle. The Unisense microsensor was tested in the gracilis muscle of six anaesthetized pigs subjected to varying degrees of muscle ischemia. We found that both tissue flow and pO2 declined in synchrony with reduced blood flow to the lower extremities. All the data from the Unisense microsensor show the same trend as the Xenon data and thus confirms that the microsensor can measure changes in tissue flow.

Free oscillation rheometry (FOR) using the ReoRox 4 instrument makes it possible, at bedside, to study the coagulation process in blood over time and gives information on clotting time and coagulum elastic properties. In order to find out how various factors influence the FOR analysis we studied the coagulation process and change of elasticity over time in non-anticoagulated and citrated blood samples, plasma samples with various platelet concentrations (0-200 x 109/l) and blood samples with various haematocrit (0-40%). Blood samples supplemented with fibrinogen were analysed to elucidate the importance of fibrinogen on elasticity. The importance of the GPIIb/IIIa receptor on platelets was investigated by comparing the elasticity development in blood samples in presence and absence of a GPIIb/IIIa receptor inhibitor, abciximab. Anticoagulation with citrate did not have major influence on the viscoelastic properties of the coagulum. Increasing number of platelets and increasing fibrinogen concentration resulted in higher elasticity while increasing haematocrit gave lower elasticity. Blood samples with GPIIb/IIIa receptor inhibitor had very low elasticity indicating the importance of functional GPIIb/IIIa receptors. In conclusion we consider FOR to be a useful method to study the elastic properties of the coagulum. Various factors such as the number of red blood cells and platelets as well as the fibrinogen concentration should be taken into consideration when evaluating the results. The ReoRox 4 instrument had excellent measuring range and unusually small artefactual effects on clot elasticity induced by the instrument in comparison with published results on other instruments.

Blood aggregation system analysis may become an effective tool for flyers health evaluation. Experimental or clinical laboratory parameters of blood coagulation and viscosity are used in the BA integral equation permitting qualitative and quantitative assessment of three biological forms of the coagulation and viscosity potential, and biochemical and biophysical protection potential. The method features accurate diagnostics of the body functions and choice of adequate treatment of BA disorders caused by dysfunctional viscera and tissues.

Implantable ventricular assist devices have been regarded as a promising instrument in the clinical treatment of patients with severe heart failures. In this article, a three-dimensional model of the Kyoto-NTN magnetically suspended centrifugal blood pump was generated and a computational fluid dynamics solution of the inner flow field of the pump including the static pressure distributions, velocity profiles, and the shear stress distributions of the blood was presented. The results revealed that reverse flow generally occurred in the impeller blade channels during the operation of the pump, due to the imbalance of the flow and the pressure gradient generated in the blade channels. The flow pattern at the exit of the blade channels was varying with its angular positions in the pump. The reverse flow at the exit of the impeller blade channels was found to be closely related with the static pressure distribution in the volute passage. Higher pressure in the volute caused severe backflow from the volute into the blade channels. To clarify the effects of a moving impeller on the blood, shear stresses of the blood in the pump were investigated according to the simulation results. The studies indicated that at the beginning of the splitter plate and the cutwater, the highest shear stress exceeded 700 Pa. At other regions such as the inlet and outlet of the impeller blade channels and some regions in the volute passage, shear stresses were found to be about 200 Pa. These areas are believed to have a high possibility of rendering blood trauma.

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.

To investigate shear stress-induced platelet activation, the cone-plate viscometer or the Couette rotational viscometer has been widely used. In a previous report, it was shown that shearing platelet-rich plasma using a Couette rotational viscometer could lead to an increase in pH by CO(2) release. However, any clear mechanism has not been provided. In this study, we examined whether shearing cell free plasma only using a cone-plate viscometer can also induce pH increase and studied the underlying mechanism of shear-induced pH increase by directly measuring total CO(2) (T(CO(2))) and CO(2) tension (P(CO(2))). When human plasma was sheared using a cone-plate viscometer, the pH of the human plasma increased time- and shear rate-dependently. Although T(CO(2)) of human plasma was not affected, P(CO(2)) was decreased by shearing, indicating that the decreased P(CO(2)) is associated with a pH increase of plasma. In addition, the pH of bicarbonate-containing suspension buffer was also shown to be increased by shearing; suggesting that the platelet studies using suspension buffers containing bicarbonate could be affected similarly. The effects of pH changes on shear stress-induced platelet activation were also investigated in the same in vitro systems. While shear stress-induced platelet aggregation was not affected by the pH changes, P-selectin expression was significantly increased in accordance with the pH increase. In conclusion, shear stress using a cone-plate viscometer induces pH increase in plasma or bicarbonate-containing suspension buffer through a P(CO(2)) decrease and the pH changes alone can contribute to platelet activation by enhancing shear stress-induced P-selectin expression.

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.

A viscometer for bedside blood measurements was developed, consisting of an oscillating resonator probe mounted directly into a disposable vacutainer tube for blood withdrawal. It was tested in vitro on blood samples with variable hematocrits (20-60%), increasing fibrinogen concentrations (0-20 g/l), increasing concentrations of an admixed radiographic contrast medium and erythrocyte suspensions in dextran 40 and dextran 70. Results were compared with those obtained with a conventional Couette viscometer. Oscillating viscometry yielded generally higher values than Couette viscometry, and had a good sensitivity for changes in hematocrit with a good correlation between the two methods (r=0.96, p<0.0001). Oscillating viscosity depended on the resonator frequency, it was higher at 3900 Hz than at 215 Hz, suggesting a viscoelastic behavior of blood. Erythrocyte aggregation, induced by increasing fibrinogen concentrations or dextran 70, affected oscillating viscometry. At a high frequency, i.e. a smaller penetration depth of the shear wave, oscillating viscosity tended to decrease, which suggests a depletion of the boundary layer from erythrocytes when they aggregate. At low frequency with a deeper shear wave penetration (about 50 microm), erythrocyte aggregation increased oscillating viscosity. Bedside tests in 17 patients with coronary heart disease and 10 controls confirmed the easy practicability of the test and showed lower oscillating viscosity in these patients despite higher fibrinogen concentrations presumably due to increased erythrocyte aggregation. We conclude that oscillating viscometry is an interesting bedside test, which is capable of providing new information on the biorheology of the erythrocyte-poor boundary layer near the vessel wall.

Blood hyperviscosity due to secondary erythrocytosis is a common pathologic feature of cyanotic congenital heart disease (CCHD). In CCHD, it is possible that hematological parameters other than red blood cells influence blood rheology. We measured blood passage time to evaluate the blood rheology in patients with CCHD (n=18, age: 15.3+/-11.9 years, mean +/- SD) and age-matched control subjects (n=27) using the microchannel array flow analyzer (MC-FAN), and the results [several hematological parameters, including hematocrit (Hct)] were compared. Blood passage time in the CCHD group was prolonged, compared with the control group (67.6+/-27.2 s vs. 44.6+/-6.7 s). For the CCHD group, blood passage time correlated significantly with red blood cell (RBC) count, hemoglobin (Hb) concentration, Hct, mean corpuscular hemoglobin concentration (MCHC), platelet (Plt) count, high-density lipoprotein cholesterol (HDL-C) level, and triglycerides (TG) level (RBC, r=0.77; Hb, r=0.69; Hct, r=0.73; MCHC, r=-0.64; Plt, r=-0.49; TG, r=0.53; HDL-C, r=-0.49, p<0.05 for each variable). For all 45 subjects, blood passage time correlated significantly with HbA1c level (r=0.45, p<0.01) and tissue-type plasminogen activator (t-PA) antigen level (r=0.46, p<0.01). Our results indicated that blood rheology is reduced in patients with CCHD as expressed by prolonged blood passage time, and it may be defined by several blood parameters in addition to erythrocytosis.

Clinical measurement of blood viscosity is an important parameter in the diagnosis of different diseases (e.g., diabetes, hypertension, cardiovascular diseases). The significance of blood viscosity in the microcirculatory flow is also of great importance. Thus, a simple and accurate evaluation of hemorheological properties could be an important challenge in clinical practice. Nowadays, validated measurements of plasma viscosity are commonly carried out with rotational viscometers by means of the various geometric configurations. However, red blood cells deform under mechanical force and this aspect could lead to an artificial variation in the apparent viscosity. In this work, an evaluation of a new technique for the viscosity determination is focused. In particular, a torsional oscillation viscometer was adopted (VM10AL, CBC Europe) in the presence and in the absence of stirring conditions at thermostated conditions. The profile of the rheological behaviour as a function of time was recorded and compared with that obtained using a cone-plate rotational viscometer (AR300, TA Instrument).

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.

We investigated the relationships between blood rheology assessed by microchannel method and the various hemorheologic factors in healthy subjects. One hundred seventy-six healthy volunteers (90 men and 86 women, mean age; 32.9+/-11.3 years) were participated in this study. Body weight, body mass index, red blood cell count, hematocrit, hemoglobin, white blood cell count, and platelet count, plasma fibrinogen, and fasting serum lipid and lipoprotein concentrations were measured. In order to assess blood rheology, blood passage time was determined by a microchannel method (Micro Channel Array Flow Analyzer). Age, body mass index, red blood cell count, hematocrit, hemoglobin, white blood cell count, total cholesterol, low-density lipoprotein cholesterol, and triglyceride were positively correlated with blood passage time in all subjects, respectively (p<0.01) and high-density lipoprotein cholesterol was inversely correlated with blood passage time (p<0.01). However, platelet count, and fibrinogen were not correlated with blood passage time. The present study showed that increased age, body mass index, red blood cell count, white blood cell count, total cholesterol, low-density lipoprotein cholesterol, and triglyceride and decreased high-density lipoprotein cholesterol were associated with impaired blood rheology measured by microchannel method in healthy subjects, suggesting that aging, obesity, erythrocytosis, leukocytosis, and dyslipidemia may be related to hemorheological disorders. This microchannel method may be useful to study blood rheology which may be associated with various risk factors of cardiovascular disorders.

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.

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".

As known, at the arteriolar level there is the highest resistance to the flow due to the section and to the velocity with an average pressure fall of 50 mmHg (from 85 to 35 mmHg). This resistance is expressed in sec(-1) by the ratio W/2r. This ratio is very high with an average value of 332 sec(-1) and viscosity at this high shear-rate is negligible. At the capillary level the pressure fall is 11.5 mmHg but the vascular resistance W/2r is much lower, on average 32 sec(-1). We can say that if a resistance of 333 sec(-1) corresponds with a pressure fall of 50 mmHg, then a resistance of 32 sec(-1) should correspond with a pressure fall of 4.8 mmHg. The highest pressure fall is due to another kind of resistance which we can define as "Capillary Blood Viscosity" because it depends on the rheological and structural characteristics of the blood. Our instrument reproduces the structure of the capillary district in an experimental model and measures the General Blood Viscosity (GBV) and the Capillary Blood Viscosity (CBV) at the same shear-rate and in particular at the low shear-rate when in non-Newtonian fluids the highest increase in viscosity appears. Consequently, at the capillary, viscosity is dominant with respect to the other geometric and physical resistances. Moreover, the percentage ratio between the GBV and the CBV gives a physical measure of erythrocyte deformability. Knowing viscosity at shear-rate present in the circulatory system, we can obtain the size of RBCs aggregates in the different circulatory districts and their characteristics expressed like "aggregation bond". Changes in CBV are the only possibility in clinical practice to improve the circulatory flow in the capillary district because it is not sure that changes in the arteriolar section can improve the capillary flow or rather open arterio-venous anastomosis. Moreover, in the systemic circulation the aggregate size allows us to point out the phenomenon of cell adhesion because the presence of several receptors involves also the other blood cells. Finally the size and the stability of the RBCs aggregates can modify the endothelial thrombo-resistance.

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.

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.