Flow Loop Model Research Articles

A handsewn pericardial valved pulmonary conduit: pulsatile flow loop in vitro and acute porcine in vivo evaluation.

Right ventricle to pulmonary artery anatomic discontinuity is common in complex congenital heart malformations. Handsewn conduits are a practised method of repair. In a proof-of-concept study, we evaluated pulmonary valve replacement with a handsewn pericardial valved pulmonary conduit in vitro and in vivo. A pulsatile flow-loop model (in vitro) and an acute 60-kg porcine model (in vivo) were used. With echocardiography and pressure catheters, baseline geometry and fluid dynamics were measured. The pulmonary valve was replaced with a handsewn glutaraldehyde-treated pericardial valved pulmonary conduit corresponding to a 21-mm prosthetic valve, after which geometric measurements and fluid dynamics were reassessed. In vitro, 15 pulmonary trunks at 4 l/min and 13 trunks at 7 l/min, and in vivo, 11 animals were investigated. The valved pulmonary conduit was straightforward to produce at the operating table and easy to suture in place. All valves were clinically sufficient in vitro and in vivo. The mean transvalvular pressure gradient in the native valve and the conduit was 8 mmHg [standard deviation (SD): 2] and 7 mmHg (SD: 2) at 4 l/min in vitro, 19 mmHg (SD: 3) and 17 mmHg (SD: 4) at 7 l/min in vitro and 3 mmHg (SD: 2) and 6 mmHg (SD: 3) in vivo. Our proof-of-concept demonstrates no early evidence of structural damage to the conduit, and the fluid dynamic data were acceptable. The handsewn conduit can be produced at the operating table.

Patient-specific, echocardiography compatible flow loop model of aortic valve regurgitation in the setting of a mechanical assist device.

Aortic regurgitation (AR) occurs commonly in patients with continuous-flow left ventricular assist devices (LVAD). No gold standard is available to assess AR severity in this setting. Aim of this study was to create a patient-specific model of AR-LVAD with tailored AR flow assessed by Doppler echocardiography. An echo-compatible flow loop incorporating a 3D printed left heart of a Heart Mate II (HMII) recipient with known significant AR was created. Forward flow and LVAD flow at different LVAD speed were directly measured and AR regurgitant volume (RegVol) obtained by subtraction. Doppler parameters of AR were simultaneously measured at each LVAD speed. We reproduced hemodynamics in a LVAD recipient with AR. AR in the model replicated accurately the AR in the index patient by comparable Color Doppler assessment. Forward flow increased from 4.09 to 5.61 L/min with LVAD speed increasing from 8,800 to 11,000 RPM while RegVol increased by 0.5 L/min (2.01 to 2.5 L/min). Our circulatory flow loop was able to accurately replicate AR severity and flow hemodynamics in an LVAD recipient. This model can be reliably used to study echo parameters and aid clinical management of patients with LVAD.

Trileaflet semilunar valve reconstruction: pulsatile in vitro evaluation.

OBJECTIVESResidual regurgitation is common after congenital surgery for right ventricular outflow tract malformation. It is accepted as there is no competent valve solution in a growing child. We investigated a new surgical technique of trileaflet semilunar valve reconstruction possessing the potential of remaining sufficient and allowing for some growth with the child. In this proof-of-concept study, our aim was to evaluate if it is achievable as a functional pulmonary valve reconstruction in vitro.METHODSExplanted pulmonary trunks from porcine hearts were evaluated in a pulsatile flow-loop model. First, the native pulmonary trunk was investigated, after which the native leaflets were explanted. Then, trileaflet semilunar valve reconstruction was performed and investigated. All valves were initially investigated at a flow output of 4 l/min and subsequently at 7 l/min. The characterization was based on hydrodynamic pressure and echocardiographic measurements.RESULTSEight pulmonary trunks were evaluated. All valves are competent on colour Doppler. There is no difference in mean pulmonary systolic artery pressure gradient at 4 l/min (P = 0.32) and at 7 l/min (P = 0.20). Coaptation length is increased in the neo-valve at 4 l/min (P < 0.001, P < 0.001, P = 0.008) and at 7 l/min (P < 0.001, P = 0.006, P = 0.006). A windmill shape is observed in all neo-valves.CONCLUSIONSTrileaflet semilunar valve reconstruction is sufficient and non-stenotic. It resulted in an increased coaptation length and a windmill shape, which is speculated to decrease with the growth of the patient, yet remains sufficient as a transitional procedure until a long-term solution is feasible. Further in vivo investigations are warranted.

Demonstration of RELAP5-3D for transient analysis of a dual coolant lead lithium fusion blanket concept

Our research aims to build a multiphysics framework for transient analysis of the Dual-Coolant Lead-Lithium (DCLL) blanket design of the proposed Fusion Nuclear Science Facility (FNSF) for all Anticipated Operational Occurrences (AOOs) using Reduced Order Models (ROMs). This paper presents an assessment of using RELAP5-3D for transient thermal-hydraulic blanket analysis of the DCLL design. Preliminary validation studies for the RELAP5-3D properties were conducted using a representative vertical flow loop model and a comparison study using experimental data from thermal convection corrosion loops at ORNL. These studies inspected the thermal hydraulic response of Lead-Lithium Eutectic (PbLi) systems within the RELAP5-3D code; mainly pressure drop and heat transfer, as compared to analytical calculations and experimental data. The Magnetohydrodynamic (MHD) pressure drop effect for liquid metal under the effects of a uniform magnetic field was implemented into our models using an equivalent forms loss coefficient based on the phasic momentum equations. We verified our implementation of MHD pressure drop within RELAP5-3D using a systematic approach consisting of two studies. Models were developed to perform comparison studies using experimental data from the Argonne Liquid metal EXperiment (ALEX) facility and the Magnetohydrodynamic PbLi Experiment (MaPLE) facility. Using the developed validation basis, we built a simplified DCLL channel model within RELAP5-3D, inspected MHD pressure drop and performed transient temperature analysis. The DCLL channel model used radial heating data from the International Thermonuclear Experimental Reactor (ITER) which was normalized to the FNSF design. A representative startup transient was performed using a relative power curve based on current PWR power ramp limits. This study demonstrated that RELAP5-3D ROMs are capable of accurate transient analysis of the DCLL blanket. We have since utilized MCNP to develop heating profiles based on the FNSF design and are working toward implementing them into our DCLL model.

Development of Inspired Therapeutics Pediatric VAD: Benchtop Evaluation of Impeller Performance and Torques for MagLev Motor Design.

Despite the availability of first-generation extracorporeal mechanical circulatory support (MCS) systems that are widely used throughout the world, there is a need for the next generation of smaller, more portable devices (designed without cables and a minimal number of connectors) that can be used in all in-hospital and transport settings to support patients in heart failure. Moreover, a system that can be universally used for all indications for use including cardiopulmonary bypass (CPB), uni- or biventricular support (VAD), extracorporeal membrane oxygenation (ECMO) and respiratory assist that is suitable for use for adult, neonate, and pediatric patients is desirable. Providing a single, well designed, universal technology could reduce the incidence of human errors by limiting the need for training of hospital staff on a single system for a variety of indications throughout the hospital rather than having to train on multiple complex systems. The objective of this manuscript is to describe preliminary research to develop the first prototype pump for use as a ventricular assist device for pediatric patients with the Inspired Universal MCS technology. The Inspired VAD Universal System is an innovative extracorporeal blood pumping system utilizing novel MagLev technology in a single portable integrated motor/controller unit which can power a variety of different disposable pump modules intended for neonate, pediatric, and adult ventricular and respiratory assistance. A prototype of the Inspired Pediatric VAD was constructed to determine the hemodynamic requirements for pediatric applications. The magnitude/range of hydraulic torque of the internal impeller was quantified. The hydrodynamic performance of the prototype pump was benchmarked using a static mock flow loop model containing a heated blood analogue solution to test the pump over a range of rotational speeds (500-6000 RPM), flow rates (0-3.5L/min), and pressures (0 to ~420 mmHg). The device was initially powered by a shaft-driven DC motor in lieu of a full MagLev design, which was also used to calculate the fluid torque acting on the impeller. The pediatric VAD produced flows as high as 4.27L/min against a pressure of 127 mmHg at 6000 RPM and the generated pressure and flow values fell within the desired design specifications. The empirically determined performance and torque values establish the requirements for the magnetically levitated motor design to be used in the Inspired Universal MagLev System. This next step in our research and development is to fabricate a fully integrated and functional magnetically levitated pump, motor and controller system that meets the product requirement specifications and achieves a state of readiness for acute ovine animal studies to verify safety and performance of the system.

Acute thrombogenicity of fluoropolymer coated stents versus competitive drug-eluting stents under single antiplatelet therapy

BackgroundRecent clinical studies have suggested the feasibility of 1-month dual antiplatelet therapy (DAPT) for patients receiving drug-eluting stent (DES). Although our previous ex-vivo swine arteriovenous (AV) shunt studies under low dose heparin treatment suggested superior thromboresistance of fluoropolymer-coated everolimus-eluting stent (FP-EES) when compared to other polymer-based DESs, the relative thromboresistance of different DESs under single antiplatelet therapy (SAPT) has never been examined. This study aimed to evaluate platelet adhesion under SAPT in competitive DESs in the in vitro flow loop model and ex vivo swine AV shunt model. MethodsThe thrombogenicity of FP-EES, BioLinx polymer zotarolimus-eluting stent (BL-ZES), and biodegradable polymer everolimus-eluting stent (BP-EES) was assessed acutely using the swine AV shunt model under aspirin or clopidogrel SAPT. Stents were immunostained using antibodies against platelets and inflammatory markers and evaluated by confocal microscopy. Also, the adhesion of platelet and albumin on the three DESs was assessed by an in-vitro flow loop model using human platelets under aspirin SAPT and fluorescent albumin, respectively. ResultsIn the shunt model, FP-EES showed significantly less platelet and inflammatory cell adhesion than BL-ZES and BP-EES. In the flow loop model, FP-EES showed significantly less platelet coverage and more albumin adsorption than BL-ZES and BP-EES. ConclusionsThese results suggest FP-EES may have particular advantage for short-term DAPT compared to other DESs.

Thromboresistance and endothelial healing in polymer-coated versus polymer-free drug-eluting stents: Implications for short-term dual anti-platelet therapy

BackgroundShort-term dual antiplatelet therapy (DAPT) is a suitable strategy after stent implantation especially in patients at high risk for bleeding. The thromboresistant characteristics and the healing profile permanent polymer stents such as the Resolute Onyx- drug-eluting stent (DES) has never been tested against the current approved stents for short-term DAPT, the polymer free (PF) biolimus-eluting stent (PF-BES) and bare metal stents (BMS) in dedicated preclinical models. MethodsAn ex-vivo porcine arteriovenous shunt and in-vivo flow loop model were used to evaluate thromboresistance. The healing profile was assessed in the rabbit model at 28 days by confocal microscopy (CM), scanning electron microscopy (SEM) and histology. Onyx-DES was separately compared with Onyx-BMS in first experiment and PF-BES in second experiment. ResultsIn an ex-vivo shunt model, CM and SEM showed significantly less platelet adhesion for Onyx-DES relative to Onyx-BMS and PF-BES. In a flow loop model using human blood, platelet adhesion was also significantly less in Onyx-DES as compared to PF-BES and Onyx-BMS. In the healing study, Onyx-BMS showed significantly greater healing profile relative to Onyx-DES as expected, whereas Onyx-DES showed equivalent endothelial coverage by SEM and significantly less Evan's blue uptake and comparable colocalization of p120 and vascular endothelial-cadherin when compared with PF-BES. ConclusionsOnyx-DES showed qualities of thomboresistance and healing which appear to be compatible with short-term DAPT. Thromboresistance was superior to PF-BES and healing was equivalent to PF-BES in this pre-clinical study. Onyx-DES might provide advantages when considering short-term DAPT especially in patients at high risk of bleeding.

Preclinical safety and efficacy evaluation of the Pipeline Vantage Embolization Device with Shield Technology

BackgroundThe Pipeline Vantage Embolization Device with Shield Technology is a next generation flow diverter developed to improve aneurysm occlusion and implant endothelialization in addition to lowering thrombogenicity. We report here...

Comparison of acute thrombogenicity and albumin adsorption in three different durable polymer coronary drug-eluting stents.

The relative thrombogenicity and albumin adsorption and retention of different durable polymers used in coronary stents has not been tested. This study sought to compare the thromboresistance and albumin binding capacity of different durable polymer drug-eluting stents (DES) using dedicated preclinical and in vitro models. In an ex vivo swine arteriovenous shunt model, a fluoropolymer everolimus-eluting stent (FP-EES) (n=14) was compared with two durable polymer DES, the BioLinx polymer-coated zotarolimus-eluting stent (BL-ZES) (n=9) and a CarboSil elastomer polymer-coated ridaforolimus-eluting stent (EP-RES) (n=6), and bare metal stents (BMS) (n=10). Stents underwent immunostaining using a cocktail of antiplatelet antibodies and a marker for inflammation and were then evaluated by confocal microscopy (CM). Albumin retention was assessed using a flow loop model with labelled human serum albumin (FP-EES [n=8], BL-ZES [n=4], EP-RES [n=4], and BMS [n=7]), and scanned by CM. The area of platelet adherence (normalised to total stent surface area) was lower in the order FP-EES (9.8%), BL-ZES (32.7%), EP-RES (87.6%) and BMS (202.0%), and inflammatory cell density was least for FP-EES <BL-ZES <EP-RES <BMS. Although nearly full coverage by albumin binding was shown for all durable polymer DES, FP-EES showed significantly greater intensity of albumin as compared to BL-ZES, EP-RES and BMS (FP-EES 79.0%; BL-ZES 13.2%; EP-RES 6.1%; BMS 1.5%). These results suggest that thromboresistance and albumin retention vary by polymer type and that these differences might result in different suitability for short-term dual antiplatelet therapy.

Hemocompatibility Testing of Blood-Contacting Implants in a Flow Loop Model Mimicking Human Blood Flow

Hemocompatibility Testing of Blood-Contacting Implants in a Flow Loop Model Mimicking Human Blood Flow

Hemocompatibility Testing of Blood-Contacting Implants in a Flow Loop Model Mimicking Human Blood Flow.

The growing use of medical devices (e.g., vascular grafts, stents, and cardiac catheters) for temporary or permanent purposes that remain in the body's circulatory system demands a reliable and multiparametric approach that evaluates the possible hematologic complications caused by these devices (i.e., activation and destruction of blood components). Comprehensive in vitro hemocompatibility testing of blood-contacting implants is the first step towards successful in vivo implementation. Therefore, extensive analysis according to the International Organization for Standardization 10993-4 (ISO 10993-4) is mandatory prior to clinical application. The presented flow loop describes a sensitive model to analyze the hemostatic performance of stents (in this case, neurovascular) and reveal adverse effects. The use of fresh human whole blood and gentle blood sampling are essential to avoid the preactivation of blood. The blood is perfused through a heparinized tubing containing the test specimen by using a peristaltic pump at a rate of 150 mL/min at 37 °C for 60 min. Before and after perfusion, hematologic markers (i.e., blood cell count, hemoglobin, hematocrit, and plasmatic markers) indicating the activation of leukocytes (polymorphonuclear [PMN]-elastase), platelets (β-thromboglobulin [β-TG]), the coagulation system (thombin-antithrombin III [TAT]), and the complement cascade (SC5b-9) are analyzed. In conclusion, we present an essential and reliable model for extensive hemocompatibility testing of stents and other blood-contacting devices prior to clinical application.

Abstract No. 588 A thromboresistant hydrogel material for vascular access

The peripherally inserted central catheter (PICC) has become increasingly popular over recent years as an alternative for venous access over traditional central venous lines. However, PICCs are more than twice as likely to experience catheter-related thrombus leading to dysfunction, infection, loss of central venous flow, or upper extremity deep vein thrombosis. Access Vascular, Inc.’s HydroPICC™ device is constructed of a proprietary combination of biocompatible polymers to create a high-strength thromboresistant hydrogel. Quantification of the thromboresistance of the HydroPICC material was evaluated in this work using established in vitro and in vivo models. Thrombus accumulation and platelet adhesion were assessed by Thrombodyne, Inc., using an in vitro blood flow loop model against two competitors (Bard PowerPICC & Navilyst BioFlo). In vivo assessment of the HydroPICC device thrombogenicity was evaluated in an ovine jugular model. The HydroPICC and BioFlo devices were found to exhibit a statistically significant reduction of thrombus formation compared to PowerPICC based on a paired, two-sided t-test (p-values of 0.017 and 0.035, respectively). The HydroPICC device was also found to exhibit a statistically significant decrease in thrombus accumulation when compared to BioFlo (p-value of 0.033). Six of the seven HydroPICC devices implanted in the ovine jugular model exhibited a sheath extending no more than 10-15% of the total length of the catheter after 14- and 28-days in vivo. This sheath was observed to be non-adherent and slid off with minimal force during explantation. The main bodies of all the implanted HydroPICC devices showed no signs of thrombosis and were functional at term. On average, the HydroPICC device exhibited a 97% reduction in thrombus accumulation as compared to a conventional TPU catheter (PowerPICC), and a 64% reduction in thrombus accumulation as compared to a fluoro-oligomer modified TPU catheter (BioFlo) based on an in vitro blood loop model. HydroPICC devices implanted for 28-days in an ovine jugular model were found to exhibit no significant thrombus formation.

Thrombogenicity assessment of Pipeline, Pipeline Shield, Derivo and P64 flow diverters in an in vitro pulsatile flow human blood loop model.

Flow diversion is a disruptive technology for the treatment of intracranial aneurysms. However, these intraluminal devices pose a risk for thromboembolic complications despite dual antiplatelet therapy. We report the thrombogenic potential of the following flow diversion devices measured experimentally in a novel human blood in-vitro pulsatile flow loop model: Pipeline™ Flex Embolization Device (Pipeline), Pipeline™ Flex Embolization Device with Shield Technology™ (Pipeline Shield), Derivo Embolization Device (Derivo), and P64 Flow Modulation Device (P64). Thrombin generation (Mean ± SD; μg/mL) was measured as: Derivo (28 ± 11), P64 (21 ± 4.5), Pipeline (21 ± 6.2), Pipeline Shield (0.6 ± 0.1) and Negative Control (1.5 ± 1.1). Platelet activation (IU/μL) was measured as: Derivo (4.9 ± 0.7), P64 (5.2 ± 0.7), Pipeline (5.5 ± 0.4), Pipeline Shield (0.3 ± 0.1), and Negative Control (0.9 ± 0.7). We found that Pipeline Shield had significantly lower platelet activation and thrombin generation than the other devices tested (p < .05) and this was comparable to the Negative Control (no device, p > .05). High resolution scanning electron microscopy performed on the intraluminal and cross-sectional surfaces of each device showed the lowest accumulation of platelets and fibrin on Pipeline Shield relative to Derivo, P64, and Pipeline. Derivo and P64 also had higher thrombus accumulation at the flared ends. Pipeline device with Phosphorylcholine surface treatment (Pipeline Shield) could mitigate device material related thromboembolic complications.

Thrombogenicity assessment of Pipeline Flex, Pipeline Shield, and FRED flow diverters in an in vitro human blood physiological flow loop model.

Endovascular treatment of intracranial aneurysms with endoluminal flow diverters (single or multiple) has proven to be clinically safe and effective, but is associated with a risk of thromboembolic complications. Recently, a novel biomimetic surface modification with covalently bound phosphorylcholine (Shield Technology™) has shown to reduce the material thrombogenicity of the Pipeline flow diverter. Thrombogenicity of Pipeline Flex, Pipeline Shield, and Flow Redirection Endoluminal Device (FRED) in the presence of human blood under physiological flow conditions—in addition to relative increase in thrombogenicity with multiple devices—remains unknown and was investigated here. Thrombin generation (mean ± SD; μg/mL; thrombin–antithrombin complex or TAT) was measured as FRED (30.3 ± 2.9), Pipeline (13.9 ± 4.4), Pipeline Shield (0.4 ± 0.3), and negative control (no device; 0.1 ± 0.0). Platelet activation (mean ± SD; IU/μL; beta‐thromboglobulin or βTG) was measured as FRED (148 ± 45), Pipeline (92.8 ± 41), Pipeline Shield (16.2 ± 3.5), and negative control (2.70 ± 0.16). FRED was significantly more thrombogenic than Pipeline and Pipeline Shield (p < 0.05) for TAT. Additionally, Pipeline Shield had significantly lower TAT and βTG than the other devices tested (p < 0.05) and these were comparable to the negative control (p > 0.05). TAT and βTG scaled proportionately with multiple Pipeline devices (N = 6) but was unaffected by multiple Pipeline Shield (N = 6) devices—the latter being statistically similar to negative control (p > 0.05). © 2018 The Authors. Journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 3195–3202, 2018.

Quantification of thrombus formation in malapposed coronary stents deployed in vitro through imaging analysis

Stent thrombosis is a major complication of coronary stent and scaffold intervention. While often unanticipated and lethal, its incidence is low making mechanistic examination difficult through clinical investigation alone. Thus, throughout the technological advancement of these devices, experimental models have been indispensable in furthering our understanding of device safety and efficacy. As we refine model systems to gain deeper insight into adverse events, it is equally important that we continue to refine our measurement methods. We used digital signal processing in an established flow loop model to investigate local flow effects due to geometric stent features and ultimately its relationship to thrombus formation. A new metric of clot distribution on each microCT slice termed normalized clot ratio was defined to quantify this distribution. Three under expanded coronary bare-metal stents were run in a flow loop model to induce clotting. Samples were then scanned in a MicroCT machine and digital signal processing methods applied to analyze geometric stent conformation and spatial clot formation. Results indicated that geometric stent features play a significant role in clotting patterns, specifically at a frequency of 0.6225 Hz corresponding to a geometric distance of 1.606 mm. The magnitude-squared coherence between geometric features and clot distribution was greater than 0.4 in all samples. In stents with poor wall apposition, ranging from 0.27 mm to 0.64 mm maximum malapposition (model of real-world heterogeneity), clots were found to have formed in between stent struts rather than directly adjacent to struts. This early work shows how the combination of tools in the areas of image processing and signal analysis can advance the resolution at which we are able to define thrombotic mechanisms in in vitro models, and ultimately, gain further insight into clinical performance.

Nanoparticle Attachment to Erythrocyte Via the Glycophorin A Targeted ERY1 Ligand Enhances Binding without Impacting Cellular Function.

Nanoparticle (NP) attachment to biocompatible secondary carriers such as red blood cell (RBC) can prolong blood residence time of drug molecules and help create next-generation nanotherapeutics. However, little is known about the impact of RBC-targeted NPs on erythrocyte function. The objectives of this study were to develop and characterize in vitro a novel poly-L-lysine (PLL) and polyethylene glycol (PEG) copolymer-based NP containing fluorescent-tagged bovine serum albumin (BSA), and conjugated with ERY1, a 12 amino acid peptide with high affinity for the RBC membrane protein glycophorin A (ENP). Confocal and flow cytometry data suggest that ENPs efficiently and irreversibly bind to RBC, with approximately 70% of erythrocytes bound after 24 h in a physiologic flow loop model compared to 10% binding of NPs without ERY1. Under these conditions, synthesized ENPs were not toxic to the RBCs. The rheological parameters at the applied shear. (0-15 Pa) were not influenced by ENP attachment to the RBCs. However, at high concentration, the strong affinity of ENPs to the glycophorin-A reduced the deformability of the RBC. ENPs can be efficiently attached to the RBCs without adversely affecting cellular function, and this may potentially enhance circulatory half-life of drug molecules.

Feasibility of Pump Speed Modulation for Restoring Vascular Pulsatility with Rotary Blood Pumps.

Continuous flow (CF) left ventricular assist devices (LVAD) diminish vascular pressure pulsatility, which may be associated with clinically reported adverse events including gastrointestinal bleeding, aortic valve insufficiency, and hemorrhagic stroke. Three candidate CF LVAD pump speed modulation algorithms designed to augment aortic pulsatility were evaluated in mock flow loop and ischemic heart failure (IHF) bovine models by quantifying hemodynamic performance as a function of mean pump speed, modulation amplitude, and timing. Asynchronous and synchronous copulsation (high revolutions per minute [RPM] during systole, low RPM during diastole) and counterpulsation (low RPM during systole, high RPM during diastole) algorithms were tested for defined modulation amplitudes (±300, ±500, ±800, and ±1,100 RPM) and frequencies (18.75, 37.5, and 60 cycles/minute) at low (2,900 RPM) and high (3,200 RPM) mean LVAD speeds. In the mock flow loop model, asynchronous, synchronous copulsation, and synchronous counterpulsation algorithms each increased pulse pressure (ΔP = 931%, 210%, and 98% and reduced left ventricular external work (LVEW = 20%, 22%, 16%). Similar improvements in vascular pulsatility (1,142%) and LVEW (40%) were observed in the IHF bovine model. Asynchronous modulation produces the largest vascular pulsatility with the advantage of not requiring sensor(s) for timing pump speed modulation, facilitating potential clinical implementation.

Abstract 20132: Quantification of Multiple Mitral Regurgitant Jets: An in vitro Assessment of Doppler Methods Pertaining to MitraClip

Introduction: Mitraclip deployment creates a double orifice valve with multiple regurgitant jets making quantification of mitral regurgitation (MR) difficult. Hypothesis: Our objective was to evaluate the accuracy of double jet MR quantification by summation of individual jet 3D echo-derived vena contracta area (VCA) or 2D proximal isovelocity surface area (PISA) estimation of regurgitant volume (RV). Methods: In a pulsatile flow loop model, six valve constructs were evaluated with RV of 25 ml, 45 ml, and 65ml/beat. Regurgitant orifices tested were: a single circular hole (n=6), two symmetric circular holes (n=6), and an asymmetric configuration with a circular hole and an elliptical hole (n=6). RV was compared with true flow measurements from in vitro flow transducers. RV was calculated as: 1) PISA-Effective regurgitant orifice area x Doppler time velocity interval (TVI) or 2) VCA x Doppler TVI. Results: RV derived by PISA method correlated well with reference standard flow measures for both single orifice and double orifice valve constructs (R=0.96 vs R=0.90, p&lt;0.0001, respectively). PISA-RV also demonstrated a good correlation to true RV when tested through symmetric or asymmetric double orifice disks (R=0.96 vs R=0.87,p&lt;0.0001). 3D-VCA derived RV showed a superior correlation using the symmetric vs asymmetric disks (R=0.946 vs R=0.63,p&lt;0.001). Conclusions: In a pulsatile model of double orifice MR, total RV is accurately measured by summation of PISA-derived RV or VCA -derived RV from each orifice. These methods deserve further evaluation in the clinical setting.

Uremic Serum and Solutes Increase Post–Vascular Interventional Thrombotic Risk Through Altered Stability of Smooth Muscle Cell Tissue Factor

Stent thrombosis (ST), a postinterventional complication with a mortality rate of 50%, has an incidence that rises precipitously in patients at risk. Chronic renal failure and end-stage renal disease have emerged as particularly strong ST risk factors, yet the mechanism remains elusive. Tissue factor (TF) is a crucial mediator of injury-related thrombosis and has been implicated for ST. We posit that uremia modulates TF in the local vessel wall to induce postinterventional thrombosis in patients with end-stage renal disease. As a model of the de-endothelialized, postinterventional state, we exposed primary human vascular smooth muscle cells (vSMCs) pretreated with uremic serum (obtained from ESRD patients on hemodialysis) to coronary-like blood flow. vSMC TF expression, activity, stability, and posttranslational modification were examined after vSMCs were treated with uremic serum or solutes. We found significantly greater clot formation after uremic serum exposure, which was substantially reduced with the prior treatment with anti-TF neutralizing antibody. Uremic sera induced 2- to 3-fold higher TF expression and activity in vSMCs independent of diabetes mellitus. Relevant concentrations of isolated uremic solutes such as indole-3-acetic acid (3.5 μg/mL), indoxyl sulfate (25 μg/mL), and uric acid (80 μg/mL) recapitulated these effects in cell culture and the flow loop model. We show further that TF undergoes ubiquitination at baseline and that uremic serum, indole-3-acetic acid, and indoxyl sulfate significantly prolong TF half-life by inhibiting its ubiquitination. The uremic milieu is profoundly thrombogenic and upregulates vSMC TF levels by increasing TF stability and decreasing its ubiquitination. Together, these data demonstrate for the first time that the posttranslational regulation of TF in uremia may have a causative role in the increased ST risk observed in uremic patients. These data suggest that interventions that reduce vSMC TF may help to prevent ST and that uremic solutes should be considered as novel risk factors for ST in patients with chronic renal failure.

Full-Height Thermal-Hydraulic Scaling Analysis of Pb-Bi-Cooled Fast Reactor PEACER

A liquid-metal–cooled fast reactor Proliferation-resistant Environment-friendly Accident-tolerant Continuable-energy Economical Reactor (PEACER) is being developed at Seoul National University with metallic-type U-Pu-Th fuel and lead-bismuth (Pb-Bi) coolant, employing the steam-generating Rankine cycle without an intermediate loop. The natural circulation potential is a key ingredient of the liquid-metal reactor design. PEACER is designed as a loop system, which increases the natural circulation capacity and reduces the maintenance cost. This work is concerned with design of a large-scale test loop Heavy Eutectic Loop Integrated Operation System (HELIOS) to simulate thermal-hydraulic behavior of Pb-Bi in the PEACER system following a single-phase one-dimensional flow loop model. The full-height loop is being constructed for Pb-Bi natural-circulation testing and operating procedure development. Electrically heated rods are used in the heating section, and a water-cooling method is adopted in the cooling section. HELIOS has the same elevation difference between thermal centers of the heat source and heat sink but reduced piping diameters.