Hyperviscosity syndromes; hemorheology for physicians and the use of microfluidic devices.

PURPOSE OF REVIEW: Hyperviscosity syndromes can lead to significant morbidity and mortality. Existing methods to measure microcirculatory rheology are not readily available and limited in relevance and accuracy at this level. In this review, we review selected hyperviscosity syndromes and the advancement of their knowledge using microfluidic platforms. RECENT FINDINGS: Viscosity changes drastically at the microvascular level as the physical properties of the cells themselves become the major determinants of resistance to blood flow. Current, outdated viscosity measurements only quantify whole blood or serum. Changes in blood composition, cell number, or the physical properties themselves lead to increased blood viscosity. Given the significant morbidity and mortality from hyperviscosity syndromes, new biophysical tools are needed and being developed to study microvascular biophysical and hemodynamic conditions at this microvascular level to help predict those at risk and guide therapeutic treatment. SUMMARY: The use of 'lab-on-a-chip' technology continues to rise to relevance with point of care, personalized testing and medicine as customizable microfluidic platforms enable independent control of many in vivo factors and are a powerful tool to study microcirculatory hemorheology.

Biosensing of Haemorheological Properties Using Microblood Flow Manipulation and Quantification.

The biomechanical properties of blood have been used to detect haematological diseases and disorders. The simultaneous measurement of multiple haemorheological properties has been considered an important aspect for separating the individual contributions of red blood cells (RBCs) and plasma. In this study, three haemorheological properties (viscosity, time constant, and RBC aggregation) were obtained by analysing blood flow, which was set to a square-wave profile (steady and transient flow). Based on a simplified differential equation derived using a discrete circuit model, the time constant for viscoelasticity was obtained by solving the governing equation rather than using the curve-fitting technique. The time constant (λ) varies linearly with respect to the interface in the coflowing channel (ß). Two parameters (i.e., average value: <λ>, linear slope: dλdß) were newly suggested to effectively represent linearly varying time constant. <λ> exhibited more consistent results than dλdß. To detect variations in the haematocrit in blood, we observed that the blood viscosity (i.e., steady flow) is better than the time constant (i.e., transient flow). The blood viscosity and time constant exhibited significant differences for the hardened RBCs. The present method was then successfully employed to detect continuously varying haematocrit resulting from RBC sedimentation in a driving syringe. The present method can consistently detect variations in blood in terms of the three haemorheological properties.

Shear-thinning behaviour of blood in response to active hyperaemia: Implications for the assessment of arterial shear stress-mediated dilatation.

NEW FINDINGS: What is the central question of this study? Quantitative values of shear rate-specific blood viscosity and shear stress in the human macrovasculature in response to exercise hyperaemia are unknown. What is the main finding and its importance? Using the handgrip exercise model, we showed that an increase in brachial artery shear rate led to a decrease in blood viscosity, despite concomitant haemoconcentration. This shear-thinning behaviour of blood, secondary to increased erythrocyte deformability, blunted the expected increase in brachial artery shear stress based on shear rate prediction. Our data yield new insights into the magnitude and regulation of macrovascular blood viscosity and shear stress in physiological conditions of elevated metabolic demand and blood flow in humans. ABSTRACT: Blood viscosity is a well-known determinant of shear stress and vascular resistance; however, accurate quantitative assessments of shear rate-specific blood viscosity in the macrovasculature in conditions of elevated blood flow are inherently difficult, owing to the shear-thinning behaviour of blood. Herein, 12 men performed graded rhythmic handgrip exercise at 20, 40, 60 and 80% of their maximal workload. Brachial artery shear rate and diameter were measured via high-resolution Duplex ultrasound. Blood was sampled serially from an i.v. cannula in the exercising arm for the assessment of blood viscosity (cone-plates viscometer). We measured ex vivo blood viscosity at 10 discrete shear rates within the physiological range documented for the brachial artery in basal and exercise conditions. Subsequently, the blood viscosity data were fitted with a two-phase exponential decay, facilitating interpolation of blood viscosity values corresponding to the ultrasound-derived shear rate. Brachial artery shear rate and shear stress increased in a stepwise manner with increasing exercise intensity, reaching peak values of 940 ± 245 s-1 and 3.68 ± 0.92 Pa, respectively. Conversely, brachial artery shear rate-specific blood viscosity decreased with respect to baseline values throughout all exercise intensities by ∼6-11%, reaching a minimal value of 3.92 ± 0.35 mPa s, despite concomitant haemoconcentration. This shear-thinning behaviour of blood, secondary to increased erythrocyte deformability, blunted the expected increase in shear stress based on shear rate prediction. Consequently, the use of shear stress yielded a higher slope for the brachial artery stimulus versus dilatation relationship than shear rate. Collectively, our data refute the use of shear rate to infer arterial shear stress-mediated processes.

Recanalization of Embolized Endovascular Intracranial Aneurysms and Changes in the Blood Viscosity: A Pilot Study.

BACKGROUND The purpose of our research was to evaluate the relationships between blood viscosity and recanalization of coiled intracranial aneurysms. MATERIAL AND METHODS The study included consecutives patients treated endovascularly by a team of experienced neurosurgeons and neuroradiologists due to brain aneurysm. A total of 50 patients (the average age was 57.48 years, SD=13.71) were assigned to 2 groups: group A with recanalization (4 male and 8 female patients) and group B without recanalization (10 male and 28 female patients) were examined. All patients underwent a 6-month follow-up of the whole-blood viscosity test with a Brookfield DV III+pro cone-plate viscometer using the Rheocalc program. Differences between groups were assessed using the Statistica 12 computer program (StatSoft Inc., Tulsa, OK, USA). RESULTS Studies have shown no significant difference in the age range between group A and B (P=0.31). In group A, higher viscosity values were found for whole blood [median: 4.14 dyn×sec/cm² (mPa×sec) quartile range 0.42], compared to group B [median: 3.92 dyn×sec/cm² (mPa×sec); quartile range 0.40; (P=0.04)]. This difference was significant (P=0.04). Additionally, the level of hematocrit was positively related with recanalization, the higher the hematocrit, the more frequent recanalization. A very strong and statistically significant relationship occurred between the frequency of recanalization and smoking (P<0.001). CONCLUSIONS The occurrence of higher values of whole blood viscosity which increase turbulent flow through the vessels may be a risk for recanalization of the coiled intracranial aneurysm.

Computational modeling of the Food and Drug Administration's benchmark centrifugal blood pump.

In order to simulate hemodynamics within centrifugal blood pumps and to predict pump hemolysis, CFD simulations must be thoroughly validated against experimental data. They must also account for and accurately model the specific working fluid in the pump, whether that is a blood-analog solution to match an experimental PIV study or animal blood in a hemolysis experiment. Therefore, the Food and Drug Administration (FDA) benchmark centrifugal blood pump and its database of experimental PIV and hemolysis data were used to thoroughly validate CFD simulations of the same blood pump. A Newtonian blood model was first used to compare to the PIV data with a blood analog fluid while hemolysis data were compared using a power-law hemolysis model fit to porcine blood data. A viscoelastic blood model was then incorporated into the CFD solver to investigate the importance of modeling blood's viscoelasticity in centrifugal pumps. The established computational framework, including a dynamic rotating mesh, animal blood-specific fluid properties and hemolysis modeling, and a k-ω SST turbulence model, was shown to more accurately predict pump pressure heads, velocity fields, and hemolysis compared to previously published CFD studies of the FDA centrifugal pump. The CFD simulations were able to match the FDA pressure and hemolysis data for multiple pump operating conditions, with the CFD results being within the standard deviations of the experimental results. While CFD radial velocity profiles between the impeller blades also compared well to the PIV velocity results, more work is still needed to address the large variability among both experimental and computational predictions of velocity in the diffuser outlet jet. Small differences were observed between the Newtonian and viscoelastic blood models in pressure head and hemolysis at the higher flow rate cases (FDA Conditions 4 and 5) but were more significant at lower flow rate and pump impeller speeds (FDA Condition 1). These results suggest that the importance of accounting for blood's viscoelasticity may be dependent on the specific blood pump operating conditions. This detailed computational framework with improved modeling techniques and an extensive validation procedure will be used in future CFD studies of centrifugal blood pumps to aid in device design and predictions of their biological responses.

High-intensity interval training irrespective of its intensity improves markers of blood fluidity in hypertensive patients.

Aim: The present study examined and compared the effects of two different HIIT (High-intensity interval training) protocols on markers of blood fluidity in hypertensive patients.Methods: Thirty hypertensive (stage 1, systolic BP >140 and diastolic BP>90 mmHg) patients (age, 47.96 ± 3.20 yrs), were randomly allocated to short-duration HIIT (SDHIIT, n = 10), long-duration HIIT (LDHIIT, n = 10), and control (n = 10) groups. After 2 weeks of continuous mild training, patients in SDHIIT group performed 8 weeks of HIIT included 27 min HIIT that encompassed 27 repetitions of 30 s activity at 80%-100% of VO2peak interspersed by 30 s passive/active (10%-20% of VO2peak) recovery, while, patients in LDHIIT group performed 8 weeks of HIIT (32 min per session) included 4 repetitions of 4 min activity at 75%-90% of VO2peak interspersed by 4 min passive/active (15%-30% of VO2peak) recovery. Two blood samples were taken before and after training and were analyzed for hemorheological variables.Results: Significant (P < .05) reductions in systolic blood pressure (SBP), blood and plasma viscosity, fibrinogen concentration and red blood cell (RBC) aggregation (8-12%) were found following two training protocols (P < .05), though, the differences between adaptations were not statistically significant (P > .05). In addition, HIIT protocols increased RBC deformability significantly (P < .05), with no significant differences being observed between two protocols.Conclusion: It is concluded that HIIT training reduces SBP and markers of blood fluidity in patients with stage 1 hypertension irrespective of the HIIT intensity and duration. Therefore, this type of exercise training could be prescribed for improving the blood fluidity markers in hypertensive patients.

Ultrasound Standing Wave-Based Cell-to-liquid Separation for Measuring Viscosity and Aggregation of Blood Sample.

When quantifying mechanical properties of blood samples flowing in closed fluidic circuits, blood samples are collected at specific intervals. Centrifugal separation is considered as a required procedure for preparing blood samples. However, the use of centrifuge is associated with several issues, including the potential for red blood cell (RBC) lysis, clotting activation, and RBC adhesions in the tube. In this study, an ultrasonic transducer is employed to separate RBCs or diluent from blood sample. The ultrasonic radiation force is much smaller than the centrifugal force acting in centrifuge, it can avoid critical issues occurring under centrifuge. Then, the RBC aggregation and blood viscosity of the blood sample are obtained using the microfluidic technique. According to the numerical results, ultrasonic transducers exhibited a maximum quality factor at an excitation frequency of 2.1 MHz. Periodic pattern of acoustic pressure fields were visualized experimentally as a column mode. The half wavelength obtained was as 0.5 λ = 0.378 ± 0.07 mm. The experimental results agreed with the analytical estimation sufficiently. An acoustic power of 2 W was selected carefully for separating RBCs or diluent from various blood samples (i.e., Hct = 20% ~ 50%; diluent: plasma, 1x phosphate-buffered saline (PBS), and dextran solution). The present method was employed to separate fixed blood samples which tended to stack inside the tube while using the centrifuge. Fixed RBCs were collected easily with an ultrasonic transducer. After various fixed blood samples with different base solutions (i.e., glutaraldehyde solution, 1x PBS, and dextran solution) were prepared using the present method, RBC aggregation and the viscosity of the blood sample are successfully obtained. In the near future, the present method will be integrated into ex vivo or in vitro fluidic circuit for measuring multiple mechanical properties of blood samples for a certain longer period.

Estimation Methods for Viscosity, Flow Rate and Pressure from Pump-Motor Assembly Parameters.

Blood pumps have found applications in heart support devices, oxygenators, and dialysis systems, among others. Often, there is no room for sensors, or the sensors are simply unreliable when long-term operation is required. However, control systems rely on those hard-to-measure parameters, such as blood flow rate and pressure difference, thus their estimation takes a central role in the development process of such medical devices. The viscosity of the blood not only influences the estimation of those parameters but is often a parameter that is of great interest to both doctors and engineers. In this work, estimation methods for blood flow rate, pressure difference, and viscosity are presented using Gaussian process regression models. Different water-glycerol mixtures were used to model blood. Data was collected from a custom-built blood pump, designed for intracorporeal oxygenators in an in vitro test circuit. The estimation was performed from motor current and motor speed measurements and its accuracy was measured for: blood flow rate r2 = 0.98, root mean squared error (RMSE) = 46 mL.min-1; pressure difference r2 = 0.98, RMSE = 8.7 mmHg; and viscosity r2 = 0.98, RMSE = 0. 0.049 mPa.s. The results suggest that the presented methods can be used to accurately predict blood flow rate, pressure, and viscosity online.

Stored platelet number and viscoelastic maximum amplitude are not altered by warming or rapid infusion.

BACKGROUND: Platelet transfusion is an important aspect of hemostatic resuscitation. Leading textbooks recommend never infusing platelets through warmers or rapid infusers, but there is no evidence to justify this position. MATERIALS AND METHODS: We obtained units of apheresis platelets in plasma from our hospital blood bank and drew a baseline sample from every unit. In the warmer arm, an aliquot from each unit was injected into a fluid warmer heated to 41°C (Ranger, 3M Corporation). After 5 minutes' incubation, the aliquot was withdrawn and sampled. In the infuser arm, we ran the remainder of the unit through a rapid infuser (RI-2, Belmont Instrument Corporation) at 500 mL/min while warmed, and obtained a sample from the outflow line. A platelet count and viscoelastic maximum amplitude (Haemonetics) was measured from every sample. RESULTS: We observed no clotting or device malfunctions. Average postwarmer temperature was 41.8°C (range, 41.0-43.0). There was no significant difference in postwarmer platelet count or viscoelastic maximum amplitude. Average postinfuser temperature was 37.4°C (range, 36.1-39.0). All units reached the goal infusion rate of 500 mL/min. There was a small increase in postinfuser platelet count. There was no significant change in postinfuser viscoelastic maximum amplitude. CONCLUSION: We were unable to detect any effect of warming or rapid infusion on the number or viscoelastic maximum amplitude of stored apheresis platelets. Contrary to common teaching, these results suggest that rapid infusion and warming does not meaningfully harm apheresis platelets.

Fast Interpretation of Thromboelastometry and Aggregometry in Patients Suffering from Chronic Liver Disease.

BACKGROUND: Collective specific variegated alterations in the hemostatic system cast doubt on the uncritical usage of standard hemotherapy algorithms in patients with chronic liver disease. The aims of the present study were to examine the applicability of commonly used early viscoelastic parameters in this particular collective and to develop first-time thresholds for the early detection of clinically relevant platelet dysfunction. METHODS: Patients suffering from advanced chronic liver disease were enrolled in this prospective single-centre study and consecutively allocated to Group 1 (MELD (Model for End-Stage Liver Disease) score 6 - 11) or Group 2 (MELD score > 16). We performed conventional laboratory coagulation analyses, as well as viscoelastometry (ROTEM®, EXTEM test, and FIBTEM test) and aggregometry (Multiplate®, ASPItest, and ADPtest), in each patient to analyze their hemostatic capacity. We analyzed the association between the A10 values (clot firmness 10 minutes after the initiation of clot building) in the EXTEM and FIBTEM tests and the corresponding Maximum Clot Firmness (MCF) values and performed receiver operating characteristic (ROC) curve analyses to investigate the ability of early parameters from the ASPItest and ADPtest (Aggregation Units (AU) 1 minute (T1), 2 minutes (T2) and 3 minutes (T3) after induction of platelet aggregation) of the Multiplate® system to predict clinically relevant platelet dysfunction. RESULTS: In the complete study collective (n = 50) and in Group 1 and Group 2 (each n = 25), A10 values correlated highly significantly with corresponding MCF values. The bias between the A10 and the MCF values was 5.1 ± 2.4 mm and 1.2 ± 1.1 mm for the EXTEM test and FIBTEM test, respectively. The highest sensitivity and specificity values for the prediction of clinically relevant platelet dysfunction at measuring point T3 were analyzed to be the values 54.9 AU/min in the ASPItest and 50.1 AU/min in the ADPtest. CONCLUSIONS: The results of the study indicate that the basic principle of using the A10 values as so-called early vis-coelastic parameters for the estimation of MCF values is legitimate. The presumably divergent bias between the A10 and MCF values necessitates the development of collective specific thresholds in hemotherapy algorithms for coagulopathic patients suffering from advanced chronic liver disease.

Plasmapheresis for hypertriglyceridemia: The association between blood viscosity and triglyceride clearance rate.

OBJECTIVES: Several factors in double filtration plasmapheresis (DFPP) were associated with triglyceride (TG) clearance rate. This study examines whether baseline whole blood viscosity was a predictor for efficient TG removal. METHODS: Adult subjects who receiving DFPP for hyperlipidemia in Taoyuan General Hospital from January 2015 to March 2018 were classified into efficient and inefficient TG removal according to TG removal rate ≥50% vs <50%. TG removal rate was defined as following formula: (pre-apheresis TG- post-apheresis TG)/pre-apheresis TG. Whole blood viscosity (WBV) was estimated by following equation: WBV = 0.12 × hematocrit +0.17 × (total protein -2.07). Univariate linear regression was used to assess the association between TG removal rate and WBV. Odds ratios (ORs) and 95% confidence interval (95%CI) for associations between variables and efficient TG removal were evaluated by logistic regression model to including univariate and multivariate adjustment. RESULTS: From a total of 66 subjects receiving DFPP, 37 subjects reached efficient TG removal. The difference in pre-apheresis TG levels, hematocrit, and WBV between efficient vs. inefficient TG removal groups was 4.1 vs 6.7 mmol/L; 43.1% vs 39.5%; and 6.0cP vs 5.cP (Ps <0.05). After multivariate adjustment, WBC was a significant predictor for efficient TG removal (ORs and 95% CI were 3.192 (1.300-7.838), P < 0.05). The correlation between WBV and extraction of TG was significant (r = -0.255, P = 0.039). CONCLUSION: Hyperviscosity reduced the efficiency of TG removal in those receiving DFPP.

Serum osmolarity and blood viscosity as a potential explanation for the pathophysiology of neuroleptic malignant syndrome.

Background: Neuroleptic malignant syndrome (NMS) is a rare but life-threatening side effect. NMS patients usually develop dehydration and fluid-electrolyte imbalance. In this study, we aimed to investigate serum osmolarity and blood viscosity in patients with NMS.Methods: This was a retrospective case-control study including 32 admissions of 27 patients with the diagnosis of NMS. As a control group, 31 non-NMS episodes of hospitalizations of the same patients were included.Results: Serum osmolarity of NMS group was 301.83 ± 20.27 mOsm/L and control group was 294.20 ± 5.92 mOsm/L. Serum osmolarity of NMS group was statistically significantly higher than the controls (p = .018). Whole blood viscosity (WBV) at high shear rate (HSR) value of NMS group was 16.17 ± 1.48 and control group was 16.50 ± 1.38 (p = .331). Regarding WBV at low shear rate (LSR) values, also no statistically significant difference was observed between groups. LSR values of NMS and control group were 39.86 ± 30.11 and 47.41 ± 28.43, respectively (p = .387).Conclusions: Our findings indicate that serum osmolarity of NMS group was statistically significantly higher than the controls. In terms of blood viscosity, there was no statistically significant difference between groups. Higher serum osmolarity in NMS patients than controls may be a reflection of a relative hemoconcentration in NMS.KEY POINTSNMS is usually associated with dehydration resulting in fluid-electrolyte imbalance.We compared the NMS episodes with non-NMS hospitalizations (as control group) of the same patients.Serum osmolarity was statistically significantly higher in NMS group than the controls.There was no statistically significant difference between groups in terms of blood viscosity.

MONITORING OF HEMORHEOLOGICAL PARAMETERS IN PATIENTS WITH ATRIAL FIBRILLATION (INITIAL DATA).

The goals of this project were to determine how hemodynamics and hemorheological change in patients diagnosed with different forms of atrial fibrillation; also, how relievers of changes in fibrinogen monitoring in patients with permanent, persistent, paroxysmal forms of arrhythmias. There was examined 30 patients (the average age of patients 65). Patients and control groups have been tested the following studies: index of erythrocytes aggregability, deformability, plasma viscosity to evaluate the blood rheological parameter, also -Fibrinogen to determine of coagulation condition. The Index of the Erythrocytes aggregation was done with the system of textural analyzes. These new innovative methods "Georgian Technique" is created by Georgian scientists and they are famous in the world as direct, numeral and exact. The index of the deformation of the erythrocytes was done with filtration method. Plasma viscosity was measured in the capillary viscosimeter in 370 C. According to the obtained data patients with atrial fibrillation have the same conditions of rheological and coagulation systems, despite of the forms of the atrial fibrillation. And it is different compared to the control group. In the statistical processing of the total row of fibrinogen, the patients were divided into 3 categories. As it turned out fibrinogen and Index of erythrocytes aggregation are in a linear relationship. The quantity of fibrinogen and of erythrocytes aggregation increase simultaneously and the greater the sequential number of the category is, the changes are more pronounced. However, the change/variability of each biological parameter, as shown from our data, is not uniform and linear. The obtained results clearly illustrate the existence of two parallel mechanisms in the body. These are on the one hand the systems of coagulation, anti-coagulation and fibtinollysis. These processes are in a state of the weighted condition, and they are characterized by dynamic equilibrium. On the other hand, the rheology system, which involves the combination of blood flow, blood velocity, vascular stiffness / elasticity, is characterized by one direction going on, with the adequacy and non-existing antipodal mechanisms. The hemorheological system does not have a physiologically balanced opposing anti-rheological system. All of this generate that the hemorheological status is very important in the development and formation of some disease. The arrangement of a rheologycal system is taking preventive character. On the one hand, the rheologycal system is a consolidation of diagnosis and evaluation of the mechanisms. Also, it is the treatment target. Normalization of them is very important in the therapeutic standpoint of the individual.

Serum IgM level as predictor of symptomatic hyperviscosity in patients with Waldenström macroglobulinaemia.

Symptomatic hyperviscosity is a common clinical manifestation in patients with Waldenström macroglobulinaemia (WM) and high serum IgM levels. Prompt intervention is required to prevent catastrophic events, such as retinal or central nervous system bleeding. Identifying patients at high risk of symptomatic hyperviscosity might support the decision to treat asymptomatic patients before irreversible damage occurs. We carried out a large retrospective study in 825 newly diagnosed WM patients, of who 113 (14%) developed symptomatic hyperviscosity. The median serum IgM level at the time of symptomatic hyperviscosity was 61·8 g/l (range 31-124 g/l). Forty-four patients (36%) had symptomatic hyperviscosity at the time of WM diagnosis. A serum IgM level >60 g/l at diagnosis was associated with a median time to symptomatic hyperviscosity of 3 months, whereas the median time for patients with serum IgM level of 50·01-60 g/l was approximately 3 years. Adjusting for other clinical factors, the odds of developing symptomatic hyperviscosity were 370-fold higher with serum IgM levels >60 g/l, and showed an association with CXCR4 mutational status. Symptomatic hyperviscosity did not impact overall survival (P = 0·12). The findings support the use of serum IgM level >60 g/l as a criterion for initiation of therapy in an otherwise asymptomatic WM patient.

Association between oxidative stress and vascular reactivity in children with sickle cell anaemia and sickle haemoglobin C disease.

Oxidative stress and haemolysis-associated nitric oxide (NO) depletion plays a crucial role in the development of vasculopathy in sickle cell anaemia (SS). However it remains unknown whether oxidative stress and haemolysis levels influence vascular function in patients with sickle haemoglobin C disease (SC). Microvascular response to heat (using Laser Doppler flowmetry on finger), oxidative stress biomarkers, NO metabolites, endothelin-1 and haematological parameters were compared between patients with SS and SC. Vascular function, oxidative and nitrosative markers were also measured in healthy (AA) children. SS and SC had increased plasma advanced oxidation protein products (AOPP), malondialdehyde, plasma antioxidant activities and NO end products, compared to AA. SC had lower catalase activity compared to AA and SS. Haemolytic rate, glutathione peroxidase and nitrotyrosine concentrations were significantly increased in children with SS compared to SC and AA. SS and SC had impaired microvascular reactivity compared to AA. In SS, the plateau phase of the response to local thermal heating was negatively associated with nitrotyrosine and AOPP. No association between vascular function parameters and oxidative stress markers was observed in SC. Mild haemolysis in SC, compared to SS, may limit oxidative and nitrosative stress and could explain the better preserved microvascular function in this group.

Assessment of viscous energy loss and the association with three-dimensional vortex ring formation in left ventricular inflow: In vivo evaluation using four-dimensional flow MRI.

PURPOSE: To evaluate viscous energy loss and the association with three-dimensional (3D) vortex ring formation in left ventricular (LV) blood flow during diastolic filling. THEORY AND METHODS: Thirty healthy volunteers were compared with 32 patients with corrected atrioventricular septal defect as unnatural mitral valve morphology and inflow are common in these patients. 4DFlow MRI was acquired from which 3D vortex ring formation was identified in LV blood flow at peak early (E)-filling and late (A)-filling and characterized by its presence/absence, orientation, and position from the lateral wall. Viscous energy loss was computed over E-filling, A-filling, and complete diastole using the Navier-Stokes energy equations. RESULTS: Compared with healthy volunteers, viscous energy loss was significantly elevated in patients with disturbed vortex ring formation as characterized by a significantly inclined orientation and/or position closer to the lateral wall. Highest viscous energy loss was found in patients without a ring-shaped vortex during E-filling (on average more than double compared with patients with ring-shape vortex, P < 0.003). Altered A-filling vortex ring formation was associated with significant increase in total viscous energy loss over diastole even in the presence of normal E-filling vortex ring. CONCLUSION: Altered vortex ring formation during LV filling is associated with increased viscous energy loss. Magn Reson Med 77:794-805, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

An Approach for Assessing Turbulent Flow Damage to Blood in Medical Devices.

In this work, contributing factors for red blood cell (RBC) damage in turbulence are investigated by simulating jet flow experiments. Results show that dissipative eddies comparable or smaller in size to the red blood cells cause hemolysis and that hemolysis corresponds to the number and, more importantly, the surface area of eddies that are associated with Kolmogorov length scale (KLS) smaller than about 10 µm. The size distribution of Kolmogorov scale eddies is used to define a turbulent flow extensive property with eddies serving as a means to assess the turbulence effectiveness in damaging cells, and a new hemolysis model is proposed. This empirical model is in agreement with hemolysis results for well-defined systems that exhibit different exposure times and flow conditions, in Couette flow viscometer, capillary tube, and jet flow experiments.

Modeling the Effect of Red Blood Cells Deformability on Blood Flow Conditions in Human Carotid Artery Bifurcation.

The purpose of this work is to predict the effect of impaired red blood cells (RBCs) deformability on blood flow conditions in human carotid artery bifurcation. First, a blood viscosity model is developed that predicts the steady-state blood viscosity as a function of shear rate, plasma viscosity, and mechanical (and geometrical) properties of RBC's. Viscosity model is developed by modifying the well-known Krieger and Dougherty equation for monodisperse suspensions by using the dimensional analysis approach. With the approach, we manage to account for the microscopic properties of RBC's, such as their deformability, in the macroscopic behavior of blood via blood viscosity. In the second part of the paper, the deduced viscosity model is used to numerically predict blood flow conditions in human carotid artery bifurcation. Simulations are performed for different values of RBC's deformability and analyzed by investigating parameters, such as the temporal mean wall shear stress (WSS), oscillatory shear index (OSI), and mean temporal gradient of WSS. The analyses show that the decrease of RBC's deformability decrease the regions of low WSS (i.e., sites known to be prevalent at atherosclerosis-prone regions); increase, in average, the value of WSS along the artery; and decrease the areas of high OSI. These observations provide an insight into the influence of blood's microscopic properties, such as the deformability of RBC's, on hemodynamics in larger arteries and their influence on parameters that are known to play a role in the initiation and progression of atherosclerosis.

[Viscoelasticity-based treatment of bleeding injuries]. / Viskoelastizitätsbasierte Therapie beim blutenden Schwerverletzten.

Uncontrolled bleeding is the leading preventable cause of death in patients with multiple injuries. Currently, trauma-induced coagulopathy is seen as an independent disease entity influencing survival. Severely bleeding trauma patients are often treated with classical blood products in predefined ratios (damage control resuscitation). Viscoelasticity-based and target-oriented approaches could possibly be given priority. Viscoelasticity-based diagnostics and therapy enable the qualitative investigation of whole blood and provide therapeutically usable information on initiation, dynamics and sustainability of thrombus formation. Due to the ease of handling and timely results this lends itself as a point-of-care procedure. This article presents the clinical issues with using viscoelastic procedures and current expert recommendations taking the literature into consideration.

Shape matters: the effect of red blood cell shape on perfusion of an artificial microvascular network.

BACKGROUND: The shape of human red blood cells (RBCs) deteriorates progressively throughout hypothermic storage, with echinocytosis being the most prevalent pathway of this morphologic lesion. As a result, each unit of stored blood contains a heterogeneous mixture of cells in various stages of echinocytosis and normal discocytes. Here we studied how the change in shape of RBCs following along the path of the echinocytic transformation affects perfusion of an artificial microvascular network (AMVN). STUDY DESIGN AND METHODS: Blood samples were obtained from healthy consenting volunteers. RBCs were leukoreduced, resuspended in saline, and treated with various concentrations of sodium salicylate to induce shape changes approximating the stages of echinocytosis experienced by RBCs during hypothermic storage (e.g., discocyte, echinocyte I, echinocyte II, echinocyte III, spheroechinocyte, and spherocyte). The AMVN perfusion rate was measured for 40% hematocrit suspensions of RBCs with different shapes. RESULTS: The AMVN perfusion rates for RBCs with discocyte and echinocyte I shapes were similar, but there was a significant decline in the AMVN perfusion rate between RBCs with shapes approximating each subsequent stage of echinocytosis. The difference in AMVN perfusion between discocytes and spherocytes (the last stage of the echinocytic transformation) was 34%. CONCLUSION: The change in shape of RBCs from normal discocytes progressively through various stages of echinocytosis to spherocytes produced a substantial decline in the ability of these cells to perfuse an AMVN. Echinocytosis induced by hypothermic storage could therefore be responsible for a similarly substantial impairment of deformability previously observed for stored RBCs.