The 12 cc Penn State pulsatile pediatric ventricular assist device: flow field observations at a reduced beat rate with application to weaning

Ventricular assist devices (VADs) have become a viable option for adult patients with end-stage heart failure during the bridge-to-transplant period and have recently shown promise in aiding in myocardial recovery. Because the number of available organs is insufficient, mechanical circulatory support systems such as VADs are also being developed for use in pediatric patients. During myocardial recovery, the system must be weaned from the patient to prepare for explant; for pulsatile devices, this often includes a reduction in flow rate, which can change the fluid dynamics of the device. These changes in flow need to be monitored because strong diastolic rotational flow, no areas of blood stasis, low blood residence time, and wall shear rates above 500 s, can help prevent thrombus deposition. Particle image velocimetry was used to observe the planar flow patterns and wall shear rates of the 12 cc Penn State Pneumatic Pediatric VAD (PVAD) at a normal operating condition and a reduced beat rate. At the reduced beat rate, the PVAD showed an earlier loss of rotational pattern, increased blood residence time, and an overall reduction in wall shear rate at the outer walls. Because this reduction in flow rate could lead to a possible increase in thrombus deposition, it may be necessary to look into other options for weaning a patient from the PVAD.     

Left ventricular assist device weaning: hemodynamic response and relationship to stroke volume and rate reduction protocols

Clinical evidence of myocardial recovery in a small cohort of patients supported with a left ventricular assist device (LVAD) has been reported. Development of an optimal LVAD weaning protocol is needed for these patients to sustain recovery after device explant. In this study, we tested the hypothesis that LVAD stroke volume reduction produces a steady-state mechanical reloading of left ventricular (LV) pressures and volumes compared with LVAD rate reduction that results in transient mechanical reloading of the heart due to beat-to-beat variation in LV pressures and volumes. The relationship of LVAD flow to LVAD stroke volume and systolic interval over a range of LVAD rates (60, 80, 100, 120, and 140 bpm) was validated in a mock circulatory flow loop. In six acute experiments, calves were implanted with a pneumatic paracorporeal LVAD (PVAD, Thoratec, Pleasanton, CA). The PVAD was operated asynchronously in the auto volume mode (full decompression) for 30 minutes to establish a baseline control condition. The calf hearts were then mechanically reloaded by LVAD rate reduction (80, 60, and 40 bpm) or LVAD stroke volume reduction (100, 120, and 140 bpm) protocols consisting of 30 minutes of support at each LVAD beat rate. The order of weaning protocols was randomized with a 30-minute recovery period (LVAD volume mode to fully decompress heart allowing it to rest) between protocols to enable return to baseline control state. Aortic pressure and flow, LV pressure and volume, pulmonary artery flow, and LVAD flow waveforms were recorded for each test condition. The LVAD stroke volume reduction protocol produced steady-state mechanical reloading compared with VAD rate reduction that resulted in transient LV mechanical reloading. This distinction is due to differences in their temporal relationships between LVAD and LV filling and emptying cycles. The acute hemodynamic benefit of LVAD stroke volume reduction was greater reduction in LV end-diastolic pressure and increase in LV segmental shortening than LVAD rate reduction. The long-term effects of steady-state and transient LV mechanical reloading on myocardial structure and function toward achieving sustained myocardial recovery warrant further investigation.     

The Influence of Device Position on the Flow Within the Penn State 12 cc Pediatric Ventricular Assist Device

Ventricular assist devices are a commonly used heart failure therapy for adult patients as bridge-to-transplant or bridge-to-recovery tools. The application of adult ventricular assist devices in pediatric patients has led to increased thrombotic events. Therefore, we have been developing a pediatric ventricular assist device (PVAD), the Penn State 12 cc PVAD. It is designed for patients with a body weight of 5-15 kg and has a stroke volume of 12 cc. Clot formation is the major concern. It is correlated to the coagulability of blood, the blood contacting materials and the fluid dynamics within the system. The intent is for the PVAD to be a long term therapy. Therefore, the system may be oriented in different positions according to the patient's behavior. This study evaluates for the first time the impact of position on the flow patterns within the Penn State 12 cc PVAD, which may help to improve the PVAD design concerning chamber and ports geometries. The fluid dynamics are visualized by particle image velocimetry. The evaluation is based on inlet jet behavior and calculated wall shear rates. Vertical and horizontal model orientations are compared, both with a beat rate of 75, outlet pressures of 90/60 mm Hg and a flow rate of 1.3 l/min. The results show a significant change of the inlet jet behavior and the development of a rotational flow pattern. Vertically, the inlet jet is strong along the wall. It initiates a rotational flow pattern with a wandering axis of rotation. In contrast, the horizontal model orientation results show a weaker inlet jet along the wall with a nearly constant center of rotation location, which can be correlated to a higher risk of thrombotic events. In addition, high speed videography illustrates differences in the diaphragm motion during diastole. Diaphragm opening trajectories measurements determine no significant impact of the density of the blood analog fluids. Hence, the results correlate to human blood.     

Flow Visualization of Three-Dimensionality Inside the 12 cc Penn State Pulsatile Pediatric Ventricular Assist Device

In order to aid the ongoing concern of limited organ availability for pediatric heart transplants, Penn State has continued development of a pulsatile Pediatric Ventricular Assist Device (PVAD). Initial studies of the PVAD observed an increase in thrombus formation due to differences in flow field physics when compared to adult sized devices, which included a higher degree of three-dimensionality. This unique flow field brings into question the use of 2D planar particle image velocimetry (PIV) as a flow visualization technique, however the small size and high curvature of the PVAD make other tools such as stereoscopic PIV impractical. In order to test the reliability of the 2D results, we perform a pseudo-3D PIV study using planes both parallel and normal to the diaphragm employing a mock circulatory loop containing a viscoelastic fluid that mimics 40% hematocrit blood. We find that while the third component of velocity is extremely helpful to a physical understanding of the flow, particularly of the diastolic jet and the development of a desired rotational pattern, the flow data taken parallel to the diaphragm is sufficient to describe the wall shear rates, a critical aspect to the study of thrombosis and design of such pumps.     

CFD analysis of a Mag-Lev ventricular assist device for infants and children: fourth generation design

Thousands of pediatric patients suffering from heart failure would benefit from longer-term mechanical circulatory support. There are, however, few support systems available in the United States as viable mechanical assist alternatives for these patients. Therefore, we have designed and developed an axial flow pediatric ventricular assist device (PVAD) with an impeller that is fully suspended by magnetic bearings. This blood pump is designed to generate 0.5-4 L/min for pressure rises of 50-95 mm Hg over 6,000-9,000 rpm. We have performed four major design iterations. Building upon the third design phase, we made improvements to create the PVAD4 model. Numerical simulations of the PVAD4 under steady flow simulations were performed to compare the predictions of the latest PVAD4 model to the earlier PVAD3 design. The PVAD4 design resulted in lower fluid stress levels and an increase in pressure generation. A blood damage analysis was also completed. As compared with the earlier PVAD3 design, the damage analysis of the PVAD4 indicated a reduction in the mean and maximum damage index for the new design. All of these numerical findings are encouraging and demonstrate progress toward achieving a superior pump design.     

Design of a continuous flow centrifugal pediatric ventricular assist device

Thousands of pediatric patients suffering from cardiomyopathy or single ventricular physiologies secondary to debilitating heart defects may benefit from long-term mechanical circulatory support due to the limited number of donor hearts available. This article presents the initial design of a fully implantable centrifugal pediatric ventricular assist device (PVAD) for 2 to 12 year olds. Conventional pump design equations, including a nondimensional scaling approach, enabled performance estimations of smaller scale versions (25 mm and 35 mm impeller diameters) of our adult support VAD. Based on this estimated performance, a computational model of the PVAD with a 35 mm impeller diameter was generated. Employing computational fluid dynamics (CFD) software, the flow paths through the PVAD and overall performance were analyzed for steady state flow conditions. The numerical simulations involved flow rates of 2 to 5 LPM for rotational speeds of 2750 to 3250 RPM and incorporated a k-epsilon fluid turbulence model with a logarithmic wall function to characterize near-wall flow conditions. The CFD results indicated best efficiency points ranging from 25% to 28%, which correlate well with typical values of blood pumps. The results further demonstrated that the pump could deliver 2 to 5 LPM at 70 to 95 mmHg for desired physiologic conditions in resting 2 to 12 year olds. Scalar stress levels remained below 300 Pa, thereby signifying potentially low levels of hemolysis. Several flow regions in the pump exhibited signs of vortices, retrograde flow, and stagnation points, which require optimization and further study. This CFD model represents a reasonable starting point for future model enhancements, leading to prototype manufacturing and experimental validation.     

Numerical design and experimental hydraulic testing of an axial flow ventricular assist device for infants and children

Mechanical circulatory support options for infants and children are very limited in the United States. Existing circulatory support systems have proven successful for short-term pediatric assist, but are not completely successful as a bridge-to-transplant or bridge-to-recovery. To address this substantial need for alternative pediatric mechanical assist, we are developing a novel, magnetically levitated, axial flow pediatric ventricular assist device (PVAD) intended for longer-term ventricular support. Three major numerical design and optimization phases have been completed. A prototype was built based on the latest numerical design (PVAD3) and hydraulically tested in a flow loop. The plastic PVAD prototype delivered 0.5-4 lpm, generating pressure rises of 50-115 mm Hg for operating speeds of 6,000-9,000 rpm. The experimental testing data and the numerical predictions correlated well. The error between these sets of data was found to be generally 7.8% with a maximum deviation of 24% at higher flow rates. The axial fluid forces for the numerical simulations ranged from 0.5 to 1 N and deviated from the experimental results by generally 8.5% with a maximum deviation of 12% at higher flow rates. These hydraulic results demonstrate the excellent performance of the PVAD3 and illustrate the achievement of the design objectives.     

Development and validation of a computational fluid dynamics methodology for simulation of pulsatile left ventricular assist devices

An unsteady computational fluid dynamic methodology was developed so that design analyses could be undertaken for devices such as the 50cc Penn State positive-displacement left ventricular assist device (LVAD). The piston motion observed in vitro was modeled, yielding the physiologic flow waveform observed during pulsatile experiments. Valve closure was modeled numerically by locally increasing fluid viscosity during the closed phase. Computational geometry contained Bjork-Shiley Monostrut mechanical heart valves in mitral and aortic positions. Cases for computational analysis included LVAD operation under steady-flow and pulsatile-flow conditions. Computations were validated by comparing simulation results with previously obtained in vitro particle image velocimetry (PIV) measurements. The steady portion of the analysis studied effects of mitral valve orientation, comparing the computational results with in vitro data obtained from mock circulatory loop experiments. The velocity field showed good qualitative agreement with the in vitro PIV data. The pulsatile flow simulations modeled the unsteady flow phenomena associated with a positive-displacement LVAD operating through several beat cycles. Flow velocity gradients allowed computation of the scalar wall strain rate, an important factor for determining hemodynamics of the device. Velocity magnitude contours compared well with PIV data throughout the cycle. Computational wall shear rates over the pulsatile cycle were found to be in the same range as wall shear rates observed in vitro.     

Computational design and experimental performance testing of an axial-flow pediatric ventricular assist device

The Virginia Artificial Heart Institute continues to design and develop an axial-flow pediatric ventricular assist device (PVAD) for infants and children in the United States. Our research team has created a database to track potential PVAD candidates at the University of Virginia Children's Hospital. The findings of this database aided with need assessment and design optimization of the PVAD. A numerical analysis of the optimized PVAD1 design (PVAD2 model) was also completed using computational fluid dynamics (CFD) to predict pressure-flow performance, fluid force estimations, and blood damage levels in the flow domain. Based on the PVAD2 model and after alterations to accommodate manufacturing, a plastic prototype for experimental flow testing was constructed via rapid prototyping techniques or stereolithography. CFD predictions demonstrated a pressure rise range of 36-118 mm Hg and axial fluid forces of 0.8-1.7 N for flows of 0.5-3 l/min over 7000-9000 rpm. Blood damage indices per CFD ranged from 0.24% to 0.35% for 200 massless and inert particles analyzed. Approximately 187 (93.5%) of the particles took less than 0.14 seconds to travel completely through the PVAD. The mean residence time was 0.105 seconds with a maximum time of 0.224 seconds. Additionally, in a water/glycerin blood analog solution, the plastic prototype produced pressure rises of 20-160 mm Hg for rotational speeds of 5960 +/- 18 rpm to 9975 +/- 31 rpm over flows from 0.5 to 4.5 l/min. The numerical results for the PVAD2 and the prototype hydraulic testing indicate an acceptable design for the pump, represent a significant step in the development phase of this device, and encourage manufacturing of a magnetically levitated prototype for animal experiments.     

A Thrombus Susceptibility Comparison of Two Pulsatile Penn State 50?cc Left Ventricular Assist Device Designs

Left ventricular assist devices (LVADs) have proven successful as bridge to transplant devices for patients awaiting donor organs. While survival rates continue to increase, destination therapy remains hindered by thrombus formation within the device. Research has shown that thrombosis is correlated to the fluid dynamics within the device and may be a result of sustained shear rates below 500?s^?1 on the polyurethane blood sac used in the Penn State pulsatile LVAD. Particle image velocimetry is used to compare flow within two 50?cc LVAD designs to assess fluid patterns and quantify wall shear rates in regions known from in vivo studies to be susceptible to thrombus formation. The two designs differ in their front face geometry. The V-1 model has an outward-facing ??dome?? whereas the face of the V-2 model is flat. A thrombus susceptibility metric, which uses measured wall shear rates and exposure times, was applied to objectively compare pump designs over the entire cardiac cycle. For each design, there are regions where wall shear rates remained below 500?s^?1 for the entire cardiac cycle resulting in high thrombus susceptibility potential. Results of this study indicate that the V-2 device had an overall lower propensity for thrombus formation in the current region of interest.     

The effects of recirculation flows on mass transfer from the arterial wall to flowing blood

Using a sudden tubular expansion as a model of an arterial stenosis, the effect of disturbed flow on mass transfer from the arterial wall to flowing blood was studied theoretically and tested experimentally by measuring the dissolution rate of benzoic acid disks forming the outer tube of a sudden tubular expansion. The study revealed that mass transfer from vessel wall to flowing fluid in regions of disturbed flow is independent of wall shear rates. The rate of mass transfer is significantly higher in regions of disturbed flow with a local maximum around the reattachment point where the wall shear rate is zero. The experimental study also revealed that the rate of mass transfer from the vessel wall to a flowing fluid is much higher in the presence of microspheres (as models of blood cells) in the flowing fluid and under the condition of pulsatile flow than in steady flow. These results imply that flow disturbance may enhance the transport of biochemicals and macromolecules, such as plasma proteins and lipoproteins synthesized within the blood vessel wall, from the blood vessel wall to flowing blood.     

Effect of shear rate on activation rate of factor X

The activation rates of Factor X in the intrinsic coagulation pathway and by RVV were measured in the stationary condition in a concentric cylinder device in a shear field and in a capillary flow reactor. The shear rates in the cylinder device were 70 and 140 sec⁻¹ and the range of the flow rate in the flow reactor was from 0.59 to 1.20 cm³/min. The activation rates in the intrinsic pathway decreased with the increase of the shear rate and therefore with the liquid flow rate. On the other hand, the rate of activation by RVV did not vary in the shear field.     

Flow Field of a Novel Implantable Valveless Counterpulsation Heart Assist Device

Flow fields are one of the key factors associated with the life threatening formation of thrombi in artificial organs. Therefore, knowledge of flow field is crucial for the design and optimization of a long-term blood pump performance. The blood chamber flow of a novel counterpulsation heart assist device (CPD) has been investigated using laser Doppler velocimetry (LDV), particle image velocimetry (PIV), and near-wall PIV (wall-PIV). The wall-PIV is an in-house developed technique assessing wall shear rates (WSR). These experimental techniques analyzed complex transient three-dimensional (3D) flow fields including major and secondary structures during the whole CPD cycle (ejection, filling, and hold time). PIV measurements in the central plane investigated an evolution (development and destruction) of the blood chamber fully filling vortex as the major CPD flow structure. The wall-PIV measurements identified areas of blood stagnation (vortex center and jet impingements) and quantified WSR at the front housing. Maximal mean WSR of 2,045 ± 605 s(-1) were found at the end of the filling. The LDV, which identified helical flow structure at the outer region of the pump, was used to complete 3D flow analysis and to combine PIV and wall-PIV results. The results suggest good washing behavior of the CPD regarding thrombus formation.     

胃肠微环境下吻合钉仿生表面对细菌黏附的微流场仿真

目的 模拟在吻合钉植入人体以后,吻合钉表面与肠壁组织之间的微流场环境,研究其仿生疏水化表面对细胞外液流速和壁面处流体剪切力的影响,进而通过流场的变化调控细菌的黏附。方法 观察鲨鱼皮肤微结构,建立细菌在微流场环境中的简化二维运动模型。通过计算流体动力学数值仿真,模拟静态流场和动态流场中,细菌分别在光滑表面和微织构表面的运动,比较两种表面环境下细菌周围的流场特征和流体剪切力,分析流体剪切力影响细菌黏附的内在机制。结果 仿生微织构的加入增强了微流场内细胞外液的流速,在静态流场中流体对细菌的黏滞作用较小;动态流场中流体对细菌的推动作用更强;一定范围内的微坑宽度使微织构壁面所受流体剪切力更大。结论 吻合钉的仿生微织构表面,加快了细胞外液的流速,提高了微织构壁面和细菌所受流体剪切力,对细菌的附着有一定影响。研究结果为吻合钉抑菌表面的研究提供了理论依据。     

A simple microfluidic device to study cell-scale endothelial mechanotransduction

Atherosclerosis is triggered by chronic inflammation of arterial endothelial cells (ECs). Because atherosclerosis develops preferentially in regions where blood flow is disturbed and where ECs have a cuboidal morphology, the interplay between EC shape and mechanotransduction events is of primary interest. In this work we present a simple microfluidic device to study relationships between cell shape and EC response to fluid shear stress. Adhesive micropatterns are used to non-invasively control EC elongation and orientation at both the monolayer and single cell levels. The micropatterned substrate is coupled to a microfluidic chamber that allows precise control of the flow field, high-resolution live-cell imaging during flow experiments, and in situ immunostaining. Using micro particle image velocimetry, we show that cells within the chamber alter the local flow field so that the shear stress on the cell surface is significantly higher than the wall shear stress in regions containing no cells. In response to flow, we observe the formation of lamellipodia in the downstream portion of the EC and cell retraction in the upstream portion. We quantify flow-induced calcium mobilization at the single cell level for cells cultured on unpatterned surfaces or on adhesive lines oriented either parallel or orthogonal to the flow. Finally, we demonstrate flow-induced intracellular calcium waves and show that the direction of propagation of these waves is determined by cell polarization rather than by the flow direction. The combined versatility and simplicity of this microfluidic device renders it very useful for studying relationships between EC shape and mechanosensitivity.     

Effect of Flow on Complex Biological Macromolecules in Microfluidic Devices

Understanding the transport, orientation, and deformation of biological macromolecules by flow is important in designing microfluidic devices. In this study, epi-fluorescence microscopy was used to characterize the behavior of macromolecules in flow in a microfluidic device, particularly how the flow affects the conformation of the molecules. The microfluidic flow path consists of a large, inlet reservoir connected to a long, rectangular channel followed by a large downstream reservoir. The flow contains both regions of high elongation (along the centerline as the fluid converges from the upstream reservoir into the channel) and shear (in the channel near the walls). Solutions of -DNA labeled with a fluorescent probe were first characterized rheologically to determine fluid relaxation times, then introduced into the microfluidic device. Images of the DNA conformation in the device were captured through an epi-fluorescent microscope. The conformation of DNA molecules under flow showed tremendous heterogeneity, as observed by Chu [7,12] and co-workers in pure shear and pure elongational flows. Histograms of the distribution of conformations were measured along the channel centerline as a function of axial position and revealed dramatic stretching of the molecules due to the converging flow followed by an eventual return to equilibrium coil size far downstream of the channel entry. The importance of shear was probed via a series of measurements near the channel centerline and near the channel wall. High shear rates near the channel wall also resulted in dramatic stretching of the molecules, and may result in chain scission of the macromolecules.     

Hemodynamically Driven Stent Strut Design

Stents are deployed to physically reopen stenotic regions of arteries and to restore blood flow. However, inflammation and localized stent thrombosis remain a risk for all current commercial stent designs. Computational fluid dynamics results predict that nonstreamlined stent struts deployed at the arterial surface in contact with flowing blood, regardless of the strut height, promote the creation of proximal and distal flow conditions that are characterized by flow recirculation, low flow (shear) rates, and prolonged particle residence time. Furthermore, low shear rates yield an environment less conducive for endothelialization, while local flow recirculation zones can serve as micro-reaction chambers where procoagulant and pro-inflammatory elements from the blood and vessel wall accumulate. By merging aerodynamic theory with local hemodynamic conditions we propose a streamlined stent strut design that promotes the development of a local flow field free of recirculation zones, which is predicted to inhibit thrombosis and is more conducive for endothelialization.     

Changes of flow characteristics by stenting in aneurysm models: influence of aneurysm geometry and stent porosity

An endovascular technique using a stent has been developed and successfully applied in the treatment of wide neck aneurysms. A stent can facilitate thrombosis in the aneurysm pouch while maintaining biocompatible passage of the parent artery. Insertion of the stent changes the flow characteristics inside the aneurysm pouch, which can affect the intra-aneurysmal embolization process. The purpose of this study is to clarify the velocity and wall shear stress changes that are caused by stenting in fusiform and lateral aneurysm models. We used a flow visualization technique that incorporated a photochromic dye in order to observe the flow fields and measure the wall shear rates. The intra-aneurysmal flow motion was significantly reduced in the stented aneurysm models. Coherent inflow along the distal wall of the aneurysm was diminished and inflow was distributed along the pores of the stent wall in the stented models. Also, sluggish intra-aneurysmal vortex motion was well maintained in the stented aneurysm models during the deceleration phase. A less porous stent generally reduced the intraneurysmal fluid motion further, but the porosity effect was not significant. The magnitude and pulsatility of the wall shear rate were reduced by stenting, and the reductions were more significant in the lateral aneurysm models compared to the fusiform aneurysm models. The hemodynamic changes that were observed in our study can help explain the efficacy of in vivo thrombus formation caused by stenting. © 2002 Biomedical Engineering Society. PAC2002: 8719Uv, 8780-y, 8719Xx     

Numerical study of turbulent blood flow through a caged-ball prosthetic heart valve using a boundary-fitted co-ordinate system

A numerical model is developed for steady turbulent flow through a fully open Starr-Edwards caged-ball prosthetic heart valve in the aortic position. An orthogonal boundary-fitted co-ordinate system is generated for the axisymmetric flow domain in the vicinity of the valve. The boundary lines follow the left ventricular wall, an idealised sinus, the aortic wall, and the ball occluder. The governing partial differentiation equations, written in a stream function-vorticity formulation, are recast into their curvilinear equivalents before being discretised into finite-difference equations. The equations are then solved iteratively. Regions of separated flow and elevated fluid stress are identified at several flow rates. Analysis of the numerical solutions reveals a simple power-law relationship between the computed turbulent shear stress and the steady flow rate at important flow field locations. The maximum turbulent shear stress occurs consistently near the sewing-ring tip. However, the peak turbulent shear stress in the sinus separation zone is observed to increase significantly with higher flow rates, exceeding values in many other regions. The numerical solutions compare satisfactorily with experimental measurements.     

Effects of mechanical valve orifice direction on the flow pattern in a ventricular assist device

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°, 45°, 90°, 135°, 180°, and 270°, where the OD opening toward the diaphragm was defined as 0°) 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°. In contrast, the regional flow velocity in this area was highest at an OD of 135°. 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°.