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    Effect of percutaneous paravalvular leak closure on hemolysis. Panaich Sidakpal S,Maor Elad,Reddy Gautam,Raphael Claire E,Cabalka Allison,Hagler Donald J,Reeder Guy S,Rihal Charanjit S,Eleid Mackram F Catheterization and cardiovascular interventions : official journal of the Society for Cardiac Angiography & Interventions OBJECTIVE:To study the effect of percutaneous paravalvular leak closure on hemolysis. BACKGROUND:Although transcatheter PVL closure reduces heart failure and mortality in symptomatic patients with paravalvular leaks (PVL), little is known about its effect on hemolysis. METHODS:We retrospectively analyzed patients undergoing transcatheter mitral or aortic PVL closure (January 2005-December 2016) at Mayo Clinic. Patients with anemia or abnormal hemolysis markers (LDH, haptoglobin) were included in the analysis. The primary outcome was defined as hemoglobin increase ≥ 1.5 mg/dL, decrease in LDH above median or improvement in haptoglobin. Univariate and multivariate binary logistic regression modeling were used to determine predictors of successful treatment of hemolysis. RESULTS:Final study population included 168 patients (130 [77%] mitral, 38 [23%] aortic PVL). Primary outcome occurred in 70 patients (42%). Hemoglobin increased by 1.74 ± 1.69 mg/dL in patients who reached primary outcome. 57/168 (34%) patients required blood transfusion prior to PVL closure compared to 35/168 (21%) postprocedure. The mean reduction in LDH was 403 U/L. Multivariate regression showed that patients with mechanical valves were more likely to have successful outcome (P = 0.044). CONCLUSION:Percutaneous PVL closure is associated with modest improvement in hemolysis markers, increase in hemoglobin levels and reduction in blood transfusion requirements. This benefit is most significant in patients with mechanical valves. 10.1002/ccd.27917
    High-Resolution Measurements of Velocity and Shear Stress in Leakage Jets From Bileaflet Mechanical Heart Valve Hinge Models. Klusak Ewa,Bellofiore Alessandro,Loughnane Sarah,Quinlan Nathan J Journal of biomechanical engineering In flow through cardiovascular implants, hemolysis, and thrombosis may be initiated by nonphysiological shear stress on blood elements. To enhance understanding of the small-scale flow structures that stimulate cellular responses, and ultimately to design devices for reduced blood damage, it is necessary to study the flow-field at high spatial and temporal resolution. In this work, we investigate flow in the reverse leakage jet from the hinge of a bileaflet mechanical heart valve (BMHV). Scaled-up model hinges are employed, enabling measurement of the flow-field at effective spatial resolution of 167 μm and temporal resolution of 594 μs using two-component particle image velocimetry (PIV). High-velocity jets were observed at the hinge outflow, with time-average velocity up to 5.7 m/s, higher than reported in previous literature. Mean viscous shear stress is up to 60 Pa. For the first time, strongly unsteady flow has been observed in the leakage jet. Peak instantaneous shear stress is up to 120 Pa, twice as high as the average value. These high-resolution measurements identify the hinge leakage jet as a region of very high fluctuating shear stress which is likely to be thrombogenic and should be an important target for future design improvement. 10.1115/1.4031350
    Multiscale modeling of hemolysis during microfiltration. Nikfar Mehdi,Razizadeh Meghdad,Paul Ratul,Liu Yaling Microfluidics and nanofluidics In this paper, we propose a multiscale numerical algorithm to simulate the hemolytic release of hemoglobin (Hb) from red blood cells (RBCs) flowing through sieves containing micropores with mean diameters smaller than RBCs. Analyzing the RBC damage in microfiltration is important in the sense that it can quantify the sensitivity of human erythrocytes to mechanical hemolysis while they undergo high shear rate and high deformation. Here, the numerical simulations are carried out via lattice Boltzmann method and spring connected network (SN) coupled by an immersed boundary method. To predict the RBC sublytic damage, a sub-cellular damage model derived from molecular dynamic simulations is incorporated in the cellular solver. In the proposed algorithm, the local RBC strain distribution calculated by the cellular solver is used to obtain the pore radius on the RBC membrane. Index of hemolysis (IH) is calculated by resorting to the resulting pore radius and solving a diffusion equation considering the effects of steric hinderance and increased hydrodynamic drag due to the size of the hemoglobin molecule. It should be mentioned that current computational hemolysis models usually utilize empirical fitting of the released free hemoglobin (Hb) in plasma from damaged RBCs. These empirical correlations contain ad hoc parameters that depend on specific device and operating conditions, thus cannot be used to predict hemolysis under different conditions. In contrast to the available hemolysis model, the proposed algorithm does not have any empirical parameters. Therefore, it can predict the IH in microfilter with different sieve pore sizes and filtration pressures. Also, in contrast to empirical correlations in which the Hb release is related to shear stress and exposure time without considering the physical processes, the proposed model links flow-induced deformation of the RBC membrane to membrane permeabilization and hemoglobin release. In this paper, the cellular solver is validated by simulating optical tweezers experiment, shear flow experiment as well as an experiment to measure RBC deformability in a very narrow microchannel. Moreover, the shape of a single RBC at the rupture moment is compared with corresponding experimental data. Finally, to validate the damage model, the results obtained from our parametric study on the role of filtration pressure and sieve pore size in Hb release are compared with experimental data. Numerical results are in good agreement with experimental data. Similar to the corresponding experiment, the numerical results confirm that hemolysis increases with increasing the filtration pressure and reduction in pore size on the sieve. While in experiment, the RBC pore size cannot be measured, the numerical results can quantify the RBC pore size. The numerical results show that at the sieve pore size of 2.2 μm above 25 cm Hg, RBC pore size is above 75 nm and RBCs experience rupture. More importantly, the results demonstrate that the proposed approach is independent from the operating conditions and it can estimate the hemolysis in a wide range of filtration pressure and sieve pore size with reasonable accuracy. 10.1007/s10404-020-02337-3
    Hemodynamic and Hematologic Effects of Histotripsy of Free-Flowing Blood: Implications for Ultrasound-Mediated Thrombolysis. Devanagondi Rajiv,Zhang Xi,Xu Zhen,Ives Kimberly,Levin Albert,Gurm Hitinder,Owens Gabe E Journal of vascular and interventional radiology : JVIR PURPOSE:To investigate the extent and consequences of histotripsy-induced hemolysis in vivo. MATERIALS AND METHODS:Porcine femoral venous blood was treated with histotripsy in 11 animals with systemic heparinization and 11 without heparin. Serum and hemodynamic measurements were obtained at 0, 2, 5, 10, 15, and 30 minutes and 48-72 hours after the procedure. Fisher exact test was used to determine differences in mortality between heparinized and nonheparinized groups. A linear mixed effects model was used to test for differences in blood analytes and hemodynamic variables over time. RESULTS:Of 11 animals in the nonheparinized group, 5 died during or immediately after histotripsy (45% nonheparin mortality vs 0% heparin mortality, P = .035). Serum hematocrit, free hemoglobin, lactate dehydrogenase (LDH), and right ventricular systolic pressure changed significantly (P < .001) over the treatment time. Serum hematocrit decreased slightly (from 32.5% ± 3.6% to 29.4% ± 4.2%), whereas increases were seen in free hemoglobin (from 6.2 mg/dL ± 4.6 to 348 mg/dL ± 100), LDH (from 365 U/L ± 67.8 ± to 722 U/L ± 84.7), and right ventricular systolic pressure (from 23.2 mm Hg ± 7.2 to 39.7 mm Hg ± 12.3). After 48-72 hours, hematocrit remained slightly decreased (P = .005), whereas LDH and free hemoglobin remained slightly increased compared with baseline (both P < .001). CONCLUSIONS:Intravascular histotripsy applied to free-flowing venous blood is safe with systemic heparinization, causing only transient hemodynamic and metabolic disturbances, supporting its use as a future noninvasive thrombolytic therapy modality. 10.1016/j.jvir.2015.03.022
    Shear stress investigation across mechanical heart valve. Zhang Pei,Yeo Joon Hock,Qian Ping,Hwang Ned H C ASAIO journal (American Society for Artificial Internal Organs : 1992) The particle image velocimetry technique was used to study the shear field across a transparent mechanical heart valve model in one cardiac cycle. Shear stress was continuously increased until peak systole and high turbulent stress was observed at the orifice of the central channel and also around the occluder trailing tips. The peak Reynolds shear stress was up to 500 N/m at peak systole, which was higher than the normal threshold for hemolysis. 10.1097/MAT.0b013e318157c093
    Red blood cell mechanical stability test. Baskurt Oguz K,Meiselman Herbert J Clinical hemorheology and microcirculation Red blood cells (RBC) are exposed to various levels of shear stress (SS) during their flow in the circulatory system, yet no significant damage occurs if their mechanical stability is not impaired. Alternatively, normal RBC may be damaged during flow in non-physiological environments and under extreme SS (e.g., extracorporeal circulation, ventricular assist devices). The shear-induced damage may result in hemolysis or in altered mechanical properties of RBC that, in turn, reduces the ability of RBC to withstand further damage by SS. An ektacytometer employing a Couette shearing system was used to apply SS at a constant level of 100 Pa for 300 seconds as a model of sub-hemolytic mechanical stress. The degree of cellular damage during and after the application was assessed by diffraction pattern analysis. The area of the diffraction pattern was found to correlate with the number of RBC in the sheared suspension. Monitoring the ellipse area during the application of gradually increasing SS provides the concentration of the remaining intact RBC and can therefore be used to estimate the hemolytic threshold as a measure of RBC mechanical stability. The hemolytic threshold determined after the mechanical stress application was found to be ~150 Pa, while it was ~250 Pa in the same samples before the SS application. Additionally, SS-elongation index curves recorded before and after the application of the sub-hemolytic SS significantly differed from each other, indicating the impairment in deformability following the mechanical stress. The Couette type ektacytometer can be used as a tool to assess the sub-hemolytic damage to RBC in testing the biomedical equipment. 10.3233/CH-131689
    Ultrasonic excitation of a bubble near a rigid or deformable sphere: implications for ultrasonically induced hemolysis. Gracewski Sheryl M,Miao Hongyu,Dalecki Diane The Journal of the Acoustical Society of America A number of independent studies have reported increased ultrasound bioeffects, such as hemolysis and hemorrhage, when ultrasound contrast agents are present. To better understand the role of cavitation in these bioeffects, one- and two-dimensional models have been developed to investigate the interactions between ultrasonically excited bubbles and model "cells." First, a simple one-dimensional model based on the Rayleigh-Plesset equation was developed to estimate upper bounds for strain, strain rate, and areal expansion of a simulated red blood cell. Then, two-dimensional boundary element models were developed (with DynaFlow Inc.) to obtain simulations of asymmetric bubble dynamics in the presence of rigid and deformable spheres. The deformable spherical "cell" was modeled using Tait's equation of state for water, with a membrane approximated by surface tension that increases linearly with areal expansion. The presence of a rigid or deformable sphere had little effect on the bubble expansion, but caused an asymmetric collapse and jetting for the conditions considered. Predicted membrane areal expansions were found to be below critical values for hemolysis reported in the literature for the cases considered near the inertial cavitation threshold. 10.1121/1.1858211
    Ovine Leukocyte Microparticles Generated by the CentriMag Ventricular Assist Device In Vitro. Pieper Ina Laura,Radley Gemma,Christen Abigail,Ali Sabrina,Bodger Owen,Thornton Catherine A Artificial organs Ventricular assist devices (VADs) are a life-saving form of mechanical circulatory support in heart failure patients. However, VADs have not yet reached their full potential due to the associated side effects (thrombosis, bleeding, infection) related to the activation and damage of blood cells and proteins caused by mechanical stress and foreign materials. Studies of the effects of VADs on leukocytes are limited, yet leukocyte activation and damage including microparticle generation can influence both thrombosis and infection rates. Therefore, the aim was to develop a multicolor flow cytometry assessment of leukocyte microparticles (LMPs) using ovine blood and the CentriMag VAD as a model for shear stress. Ovine blood was pumped for 6 h in the CentriMag and regular samples analyzed for hemolysis, complete blood counts and LMP by flow cytometry during three different pump operating conditions (low flow, standard, high speed). The high speed condition caused significant increases in plasma-free hemoglobin; decreases in total leukocytes, granulocytes, monocytes, and platelets; increases in CD45 LMPs as well as two novel LMP populations: CD11b /HLA-DR and CD11b /HLA-DR , both of which were CD14 /CD21 . CD11b /HLA-DR LMPs appeared to respond to an increase in shear magnitude whereas the CD11b /HLA-DR LMPs significantly increased in all pumping conditions. We propose that these two populations are released from granulocytes and T cells, respectively, but further research is needed to better characterize these two populations. 10.1111/aor.13068
    Comparison of ASPIRE Mechanical Thrombectomy Versus AngioJet Thrombectomy System in a Porcine Iliac Vein Thrombosis Model. Weinberg Roy J,Okada Tamuru,Chen Aaron,Kim Walter,Chen Changyi,Lin Peter H Annals of vascular surgery BACKGROUND:Percutaneous mechanical thrombectomy device has become an important therapeutic armamentarium in the management of venous thromboembolism. In this study, we compare the efficacy and safety profile of the AngioJet thrombectomy device and ASPIRE thrombectomy system in a porcine venous thrombosis model. METHODS:Twelve adult pigs underwent bilateral iliac venous thrombosis created by using a stent graft thrombosis model and subsequently underwent either AngioJet (n = 6) or ASPIRE mechanical thrombectomy (n = 6) 1 week later. Intravascular ultrasound (IVUS) was used to assess thrombectomy efficacy, and computed tomography was used to evaluate pulmonary embolism (PE). Hemolytic effect was measured by plasma-free hemoglobin (PfHgb). Iliac vein thrombogenicity was evaluated with radiolabeled platelet and fibrin deposition. Veins were harvested and evaluated with light microscopy and scanning electron microscopy (SEM). RESULTS:Similar thrombectomy efficacy by IVUS evaluation was noted in both groups. Significant greater PE and hemolysis were identified in the AngioJet group compared to the ASPIRE group. The AngioJet group had greater reduction in WBC and platelet compared to the ASPIRE group. No difference was found in thrombogenicity, light microscopic evaluation, or SEM. CONCLUSIONS:Both devices had similar thrombectomy efficacy and thrombogenicity response. The ASPIRE catheter incurred less PE and hemolysis compared to the AngioJet device. Vessel wall response by histological analysis and SEM was similar in both groups. 10.1016/j.avsg.2016.12.014
    Verification Benchmarks to Assess the Implementation of Computational Fluid Dynamics Based Hemolysis Prediction Models. Hariharan Prasanna,D'Souza Gavin,Horner Marc,Malinauskas Richard A,Myers Matthew R Journal of biomechanical engineering As part of an ongoing effort to develop verification and validation (V&V) standards for using computational fluid dynamics (CFD) in the evaluation of medical devices, we have developed idealized flow-based verification benchmarks to assess the implementation of commonly cited power-law based hemolysis models in CFD. Verification process ensures that all governing equations are solved correctly and the model is free of user and numerical errors. To perform verification for power-law based hemolysis modeling, analytical solutions for the Eulerian power-law blood damage model (which estimates hemolysis index (HI) as a function of shear stress and exposure time) were obtained for Couette and inclined Couette flow models, and for Newtonian and non-Newtonian pipe flow models. Subsequently, CFD simulations of fluid flow and HI were performed using Eulerian and three different Lagrangian-based hemolysis models and compared with the analytical solutions. For all the geometries, the blood damage results from the Eulerian-based CFD simulations matched the Eulerian analytical solutions within ∼1%, which indicates successful implementation of the Eulerian hemolysis model. Agreement between the Lagrangian and Eulerian models depended upon the choice of the hemolysis power-law constants. For the commonly used values of power-law constants (α  = 1.9-2.42 and β  = 0.65-0.80), in the absence of flow acceleration, most of the Lagrangian models matched the Eulerian results within 5%. In the presence of flow acceleration (inclined Couette flow), moderate differences (∼10%) were observed between the Lagrangian and Eulerian models. This difference increased to greater than 100% as the beta exponent decreased. These simplified flow problems can be used as standard benchmarks for verifying the implementation of blood damage predictive models in commercial and open-source CFD codes. The current study only used power-law model as an illustrative example to emphasize the need for model verification. Similar verification problems could be developed for other types of hemolysis models (such as strain-based and energy dissipation-based methods). However, since the current study did not include experimental validation, the results from the verified models do not guarantee accurate hemolysis predictions. This verification step must be followed by experimental validation before the hemolysis models can be used for actual device safety evaluations. 10.1115/1.4030823
    Assessing Computational Model Credibility Using a Risk-Based Framework: Application to Hemolysis in Centrifugal Blood Pumps. Morrison Tina M,Hariharan Prasanna,Funkhouser Chloe M,Afshari Payman,Goodin Mark,Horner Marc ASAIO journal (American Society for Artificial Internal Organs : 1992) Medical device manufacturers using computational modeling to support their device designs have traditionally been guided by internally developed modeling best practices. A lack of consensus on the evidentiary bar for model validation has hindered broader acceptance, particularly in regulatory areas. This has motivated the US Food and Drug Administration and the American Society of Mechanical Engineers (ASME), in partnership with medical device companies and software providers, to develop a structured approach for establishing the credibility of computational models for a specific use. Charged with this mission, the ASME V&V 40 Subcommittee on Verification and Validation (V&V) in Computational Modeling of Medical Devices developed a risk-informed credibility assessment framework; the main tenet of the framework is that the credibility requirements of a computational model should be commensurate with the risk associated with model use. This article provides an overview of the ASME V&V 40 standard and an example of the framework applied to a generic centrifugal blood pump, emphasizing how experimental evidence from in vitro testing can support computational modeling for device evaluation. Two different contexts of use for the same model are presented, which illustrate how model risk impacts the requirements on the V&V activities and outcomes. 10.1097/MAT.0000000000000996
    Modeling and prediction of flow-induced hemolysis: a review. Faghih Mohammad M,Sharp M Keith Biomechanics and modeling in mechanobiology Despite decades of research related to hemolysis, the accuracy of prediction algorithms for complex flows leaves much to be desired. Fundamental questions remain about how different types of fluid stresses translate to red cell membrane failure. While cellular- and molecular-level simulations hold promise, spatial resolution to such small scales is computationally intensive. This review summarizes approaches to continuum-level modeling of hemolysis, a method that is likely to be useful well into the future for design of typical cardiovascular devices. Weaknesses are revealed for the Eulerian method of hemolysis prediction and for the linearized damage function. Wide variations in scaling of red cell membrane tension are demonstrated with different types of fluid stresses when the scalar fluid stress is the same, as well as when the energy dissipation rate is the same. New experimental data are needed for red cell damage in simple flows with controlled levels of different types of stresses, including laminar shear, laminar extension (normal), turbulent shear, and turbulent extension. Such data can be curve-fit to create more universal continuum-level models and can serve to validate numerical simulations. 10.1007/s10237-019-01137-1
    A quantitative comparison of mechanical blood damage parameters in rotary ventricular assist devices: shear stress, exposure time and hemolysis index. Fraser Katharine H,Zhang Tao,Taskin M Ertan,Griffith Bartley P,Wu Zhongjun J Journal of biomechanical engineering Ventricular assist devices (VADs) have already helped many patients with heart failure but have the potential to assist more patients if current problems with blood damage (hemolysis, platelet activation, thrombosis and emboli, and destruction of the von Willebrand factor (vWf)) can be eliminated. A step towards this goal is better understanding of the relationships between shear stress, exposure time, and blood damage and, from there, the development of numerical models for the different types of blood damage to enable the design of improved VADs. In this study, computational fluid dynamics (CFD) was used to calculate the hemodynamics in three clinical VADs and two investigational VADs and the shear stress, residence time, and hemolysis were investigated. A new scalar transport model for hemolysis was developed. The results were compared with in vitro measurements of the pressure head in each VAD and the hemolysis index in two VADs. A comparative analysis of the blood damage related fluid dynamic parameters and hemolysis index was performed among the VADs. Compared to the centrifugal VADs, the axial VADs had: higher mean scalar shear stress (sss); a wider range of sss, with larger maxima and larger percentage volumes at both low and high sss; and longer residence times at very high sss. The hemolysis predictions were in agreement with the experiments and showed that the axial VADs had a higher hemolysis index. The increased hemolysis in axial VADs compared to centrifugal VADs is a direct result of their higher shear stresses and longer residence times. Since platelet activation and destruction of the vWf also require high shear stresses, the flow conditions inside axial VADs are likely to result in more of these types of blood damage compared with centrifugal VADs. 10.1115/1.4007092
    A Review of Hemolysis Prediction Models for Computational Fluid Dynamics. Yu Hai,Engel Sebastian,Janiga Gábor,Thévenin Dominique Artificial organs Flow-induced hemolysis is a crucial issue for many biomedical applications; in particular, it is an essential issue for the development of blood-transporting devices such as left ventricular assist devices, and other types of blood pumps. In order to estimate red blood cell (RBC) damage in blood flows, many models have been proposed in the past. Most models have been validated by their respective authors. However, the accuracy and the validity range of these models remains unclear. In this work, the most established hemolysis models compatible with computational fluid dynamics of full-scale devices are described and assessed by comparing two selected reference experiments: a simple rheometric flow and a more complex hemodialytic flow through a needle. The quantitative comparisons show very large deviations concerning hemolysis predictions, depending on the model and model parameter. In light of the current results, two simple power-law models deliver the best compromise between computational efficiency and obtained accuracy. Finally, hemolysis has been computed in an axial blood pump. The reconstructed geometry of a HeartMate II shows that hemolysis occurs mainly at the tip and leading edge of the rotor blades, as well as at the leading edge of the diffusor vanes. 10.1111/aor.12871
    Characterization of erythrocyte membrane tension for hemolysis prediction in complex flows. M Faghih Mohammad,Sharp M Keith Biomechanics and modeling in mechanobiology Hemolysis is a persistent issue with blood-contacting devices. Many experimental and theoretical contributions over the last few decades have increased insight into the mechanisms of hemolysis in both laminar and turbulent flows, with the ultimate goal of developing a comprehensive, mechanistic hemolysis model. Many models assume that hemolysis scales with a resultant, scalar stress representing all components of the fluid stress tensor. This study critically evaluates this scalar stress hypothesis by calculating the response of the red blood cell membrane to different types of fluid stress (laminar shear and extension, and three turbulent shear and extension cases), each with the same scalar stress. It was found that even though the scalar stress is the same for all cases, membrane tension varied by up to three orders of magnitude. In addition, extensional flow causes constant tension, while tank-treading in shear flow causes periodic tension, with tank-treading frequency varying by three orders of magnitude among the cases. For turbulent flow, tension also depends on eddy size. It is concluded, therefore, that scalar stress alone is inadequate for scaling hemolysis. Fundamental investigations are needed to establish a new index of the fluid stress tensor that provides reliable hemolysis prediction across the wide range of complex flows that occur in cardiovascular devices. 10.1007/s10237-017-0995-2
    On the representation of effective stress for computing hemolysis. Wu P,Gao Q,Hsu P-L Biomechanics and modeling in mechanobiology Hemolysis is a major concern in blood-circulating devices, which arises due to hydrodynamic loading on red blood cells from ambient flow environment. Hemolysis estimation models have often been used to aid hemocompatibility design. The preponderance of hemolysis models was formulated on the basis of laminar flows. However, flows in blood-circulating devices are rather complex and can be laminar, transitional or turbulent. It is an extrapolation to apply these models to turbulent flows. For the commonly used power-law models, effective stress has often been represented using Reynolds stresses for estimating hemolysis in turbulent flows. This practice tends to overpredict hemolysis. This study focused on the representation of effective stress in power-law models. Through arithmetic manipulations from Navier-Stokes equation, we showed that effective stress can be represented in terms of energy dissipation, which can be readily obtained from CFD simulations. Three cases were tested, including a capillary tube, the FDA benchmark cases of nozzle model and blood pump. The results showed that the representation of effective stress in terms of energy dissipation greatly improved the prediction of hemolysis for a wide range of flow conditions. The improvement increases as Reynolds number increases; the overprediction of hemolysis was reduced by up to two orders of magnitude. 10.1007/s10237-018-01108-y
    A Red Blood Cell Model to Estimate the Hemolysis Fingerprint of Cardiovascular Devices. Toninato Riccardo,Fadda Giuseppe,Susin Francesca Maria Artificial organs One of the most relevant and open issues within cardiovascular prosthetic hemodynamic performance is a realistic quantification of the damage sustained by red blood cells (RBCs). Specifically, the optimal design of bileaflet mechanical heart valves (BMHVs) requires both low shear stresses along the leaflets and short particle resident times. This study approaches RBC damage estimation by developing a numerical model of RBCs and computing the damage sustained by a set of passive RBCs immersed within in vitro flows. The RBC is modeled as an ellipsoidal shell with size dependent on age. Mechanically, a viscous hyper-elastic model was adopted to compute the stress-deformation transmitted by the experimental flow field to the RBC layer. The rupture parameters were calibrated using experimental results on real RBCs submitted to Couette flow. Moreover, the integrated hemolysis index (HI) through a BMHV was computed for a set of RBCs injected in a flow field derived from an in vitro study and for multiple RBC passages. The main results are (1) a good capability of the RBC model to replicate in vitro experiments performed with real RBCs, finding realistic rupture parameters; (2) the spatial distribution for the HI, maximal along the leaflet boundary layer and for long resident times; (3) 90% of HI is produced by the less damaging trajectories, which are favored by local flow dynamics; (4) cumulated HI in 8 days is about 0.01% smaller than the clinical warning threshold, the latter being obtained only after a period of time comparable with the RBC lifetime. 10.1111/aor.12937
    A Cellular Model of Shear-Induced Hemolysis. Sohrabi Salman,Liu Yaling Artificial organs A novel model is presented to study red blood cell (RBC) hemolysis at cellular level. Under high shear rates, pores form on RBC membranes through which hemoglobin (Hb) leaks out and increases free Hb content of plasma leading to hemolysis. By coupling lattice Boltzmann and spring connected network models through immersed boundary method, we estimate hemolysis of a single RBC under various shear rates. First, we use adaptive meshing to find local strain distribution and critical sites on RBC membranes, and then we apply underlying molecular dynamics simulations to evaluate damage. Our approach comprises three sub-models: defining criteria of pore formation, calculating pore size, and measuring Hb diffusive flux out of pores. Our damage model uses information of different scales to predict cellular level hemolysis. Results are compared with experimental studies and other models in literature. The developed cellular damage model can be used as a predictive tool for hydrodynamic and hematologic design optimization of blood-wetting medical devices. 10.1111/aor.12832
    Prediction of mechanical hemolysis in medical devices via a Lagrangian strain-based multiscale model. Nikfar Mehdi,Razizadeh Meghdad,Zhang Jiafeng,Paul Ratul,Wu Zhongjun J,Liu Yaling Artificial organs This work introduces a new Lagrangian strain-based model to predict the shear-induced hemolysis in biomedical devices. Current computational models for device-induced hemolysis usually utilize empirical fitting of the released free hemoglobin (Hb) in plasma from damaged red blood cells (RBCs). These empirical correlations contain parameters that depend on specific device and operating conditions, thus cannot be used to predict hemolysis in a general device. The proposed algorithm does not have any empirical parameters, thus can presumably be used for hemolysis prediction in various blood-wetting medical devices. In contrast to empirical correlations in which the Hb release is related to the shear stress and exposure time without considering the physical processes, the proposed model links flow-induced deformation of the RBC membrane to membrane permeabilization and Hb release. In this approach, once the steady-state numerical solution of blood flow in the device is obtained under a prescribed operating condition, sample path lines are traced from the inlet of the device to the outlet to calculate the history of the shear stress tensor. In solving the fluid flow, it is assumed that RBCs do not have any influence on the flow pattern. Along each path line, shear stress tensor will be input into a coarse-grained (CG) RBC model to calculate the RBC deformation. Then the correlations obtained from molecular dynamics (MD) simulations are applied to relate the local areal RBC deformation to the perforated area on the RBC membrane. Finally, Hb released out of transient pores is calculated over each path line via a diffusion equation considering the effects of the steric hindrance and increased hydrodynamic drag due to the size of the Hb molecule. The total index of hemolysis (IH) is calculated by integration of released Hb over all the path lines in the computational domain. Hemolysis generated in the Food and Drug Administration (FDA) nozzle and two blood pumps, that is, a CentriMag blood pump (a centrifugal pump) and HeartMate II (an axial pump), for different flow regimes including the laminar and turbulent flows are calculated via the proposed algorithm. In all the simulations, the numerical predicted IH is close to the range of experimental data. The results promisingly indicate that this multiscale approach can be used as a tool for predicting hemolysis and optimizing the hematologic design of other types of blood-wetting devices. 10.1111/aor.13663
    A strain-based model for mechanical hemolysis based on a coarse-grained red blood cell model. Ezzeldin Hussein M,de Tullio Marco D,Vanella Marcos,Solares Santiago D,Balaras Elias Annals of biomedical engineering Mechanical hemolysis is a major concern in the design of cardiovascular devices, such as prosthetic heart valves and ventricular assist devices. The primary cause of mechanical hemolysis is the impact of the device on the local blood flow, which exposes blood elements to non-physiologic conditions. The majority of existing hemolysis models correlate red blood cell (RBC) damage to the imposed fluid shear stress and exposure time. Only recently more realistic, strain-based models have been proposed, where the RBC's response to the imposed hydrodynamic loading is accounted for. In the present work we extend strain-based models by introducing a high-fidelity representation of RBCs, which is based on existing coarse-grained particle dynamics approach. We report a series of numerical experiments in simple shear flows of increasing complexity, to illuminate the basic differences between existing models and establish their accuracy in comparison to the high-fidelity RBC approach. We also consider a practical configuration, where the flow through an artificial heart valve is computed. Our results shed light on the strengths and weaknesses of each approach and identify the key gaps that should be addressed in the development of new models. 10.1007/s10439-015-1273-z