Mock Loop System Research Articles

Use of a Virtual Mock Loop model to evaluate a new left ventricular assist device for transapical insertion

We are developing a novel type of miniaturized left ventricular assist device that is configured for transapical insertion. The aim of this study was to assess the performance and function of a new pump by using a Virtual Mock Loop system for device characterization and mapping. The results, such as pressure-flow performance curves, from pump testing in a physical mock circulatory loop were used to analyze its function as a left ventricular assist device. The Virtual Mock Loop system was programmed to mimic the normal heart condition, systolic heart failure, diastolic heart failure, and both systolic and diastolic heart failure, and to provide hemodynamic pressure values before and after the activation of several left ventricular assist device pump speeds (12,000, 14,000, and 16,000 r/min). With pump support, systemic flow and mean aortic pressure increased, and mean left atrial pressure and pulmonary artery pressure decreased for all heart conditions. Regarding high pump-speed support, the systemic flow, aortic pressure, left atrial pressure, and pulmonary artery pressure returned to the level of the normal heart condition. Based on the test results from the Virtual Mock Loop system, the new left ventricular assist device for transapical insertion may be able to ease the symptoms of patients with various types of heart failure. The Virtual Mock Loop system could be helpful to assess pump performance before in vitro bench testing.

Evaluation of New Left Ventricular Assist Device for Transapical Insertion Using Virtual Mock Loop Model

Purpose The aim of this study was to assess a new pump's performance and function by using a virtual mock loop (VML) system for device characterization and mapping. Methods We are developing a novel miniaturized left ventricle assist device (LVAD) configured for transapical insertion (Perfusions Solutions Inc., South Euclid, OH). The results of pump testing in the laboratory, such as pressure-flow performance curves, were used for the analysis of its function as an LVAD. The VML system was programmed to mimic various types of heart failure and provide hemodynamic pressure values before and after activation of LVAD. The circulatory conditions of the VML system were systolic heart failure (SHF), diastolic HF (DHF), and both systolic and diastolic HF (BHF). Results Before and after pump activation with SHF condition and with a pump speed of 14000 RPM, aortic pressure (AoP) increased from 71/50 to 99/97 mm Hg, pulmonary artery pressure (PAP) changed from 44/36 to 44/33 mm Hg, mean left atrium pressure (mLAP) decreased from 25 to 18 mm Hg, mean right atrium pressure (mRAP) increased from 7 to 10 mm Hg; with DHF, AoP changed from 116/81 to 129/113 mm Hg, PAP was 45/34 to 45/31 mm Hg, mLAP was 18 to 15 mm Hg, mRAP was 10 to 12 mm Hg; with BHF, AoP was 65/46 to 98/96 mm Hg, PAP was 44/36 to 45/33 mm Hg, mLAP was 26 to 19 mm Hg, mRAP was 7 to 10 mm Hg. (Figure A; pressure-volume curve with BHF, B; pressure curve with BHF without LVAD, 14000 RPM and 16000 RPM of the pump speed) Conclusion Due to the test results from the VML system, the new LVAD for transapical insertion could have the ability enough to ease symptoms of the patients with various types of heart failure based on results from VML system.

A Novel Sensorized Heart Valve Prosthesis: Preliminary In Vitro Evaluation.

Background: Recent studies have shown that subclinical valve thrombosis in heart valve prosthesis (HVP) can be responsible for reduced leaflet motion detectable only by advanced imaging diagnostics. We conceived a novel sensorized HVP able to detect earlier any thrombus formation that may alter the leaflets motion using an electric impedance measurement, IntraValvular Impedance (IVI). Methods: For IVI measurement, dedicated electrodes are embedded in the structure of the HVP to generate a local electric field that is altered by the moving valve leaflets during their cyclic opening/closing. We present preliminary in vitro results using a first prototype of sensorized mechanical heart valve connected to an external impedance measurement system. The prototype was tested on a circulatory mock loop system and the IVI signals were recorded during both normal dynamics and experimentally induced altered working of the leaflets. Results: Recordings showed a very repetitive and stable IVI signal during the normal cyclic opening/closing of the HVP. The induced alterations in leaflet motion were reflected in the IVI signal. Conclusions: The novel sensorized HVP has great potential to give early warning of possible subclinical valve thrombosis altering the valve leaflet motion, and to help in tailoring the anticoagulation therapy.

In vitro comparison of the hemocompatibility of two centrifugal left ventricular assist devices

ObjectivesShear stress from left ventricular assist devices induces von Willebrand factor degradation and platelet dysfunction, leading to nonsurgical bleeding. We characterized the hemostatic changes induced by 2 centrifugal left ventricular assist devices, the HeartMate 3 (Abbott Inc, Chicago, Ill) and the EVAHEART (Evaheart Inc, Houston, Tex), for comparison. MethodsWhole blood from 8 healthy volunteers was used ex vivo. Blood from the same donor was used for 6 hours of circulation in a miniature mock-loop system consisting of 2 identical extracorporeal circuits to compare the following experimental settings: (1) optimal revolutions per minute (rpm) for the HeartMate 3 (n = 4; 5000 rpm) and the EVAHEART (n = 4; 2500 rpm) and (2) equal rpm (3000 rpm for the HeartMate 3 and EVAHEART, n = 4 vs n = 4). For both settings, blood flow was adjusted to 1 mock-loop filling volume per minute (HeartMate 3 = 82 mL/min, EVAHEART = 100 mL/min). A panel of coagulation markers was analyzed to investigate hemostatic changes. ResultsThe free plasma hemoglobin concentration was significantly lower in the EVAHEART compared with the HeartMate 3 after 6 hours of mock-loop circulation under both settings (optimal: 37 ± 31 vs 503 ± 173 mg/dL, P < .0001; equal: 27 ± 4 vs 139 ± 135 mg/dL, P = .024). Loss of von Willebrand factor high-molecular-weight multimers occurred in both left ventricular assist devices and settings, but the von Willebrand factor:activity/von Willebrand factor:antigen ratio after 6 hours was significantly lower in optimal settings for the HeartMate 3 (P = .009). The thrombin-antithrombin complex level was significantly lower with the EVAHEART for both settings (P < .0001). ConclusionsThe EVAHEART left ventricular assist device caused less hemolysis, resulted in lower coagulation activation, and provided better preservation of von Willebrand factor functional activity compared with the HeartMate 3 device. These findings prove that left ventricular assist device design plays a major role in minimizing blood damage during left ventricular assist device support.

Correction: Changes in aortic pulse wave velocity of four thoracic aortic stent grafts in an ex vivo porcine model.

[This corrects the article DOI: 10.1371/journal.pone.0186080.].

Changes in aortic pulse wave velocity of four thoracic aortic stent grafts in an ex vivo porcine model.

ObjectivesThoracic endovascular aortic repair (TEVAR) has been shown to lead to increased aortic stiffness. The aim of this study was to investigate the effect of stent graft type and stent graft length on aortic stiffness in a controlled, experimental setting.MethodsTwenty porcine thoracic aortas were connected to a pulsatile mock loop system. Intraluminal pressure was recorded at two sites in order to measure pulse wave velocity (PWV) for each aorta: before stent graft deployment (t1); after deployment of a 100-mm long stent graft (t2); and after distal extension through deployment of a second 100-mm long stent graft (t3). Four different types of stent grafts (Conformable Gore® TAG® Device, Bolton Relay® Device, Cook Zenith Alpha™, and Medtronic Valiant®) were evaluated.ResultsFor the total cohort of 20 aortas, PWV increased by a mean 0.6 m/s or 8.9% of baseline PWV after deployment of a 100-mm proximal stent graft (P<0.001), and by a mean 1.4 m/s or 23.0% of baseline PWV after distal extension of the stent graft (P<0.001). Univariable regression analysis showed a significant correlation between aortic PWV and extent of stent graft coverage, (P<0.001), but no significant effect of baseline aortic length, baseline aortic PWV, or stent graft type on the percentual increase in PWV at t2 or at t3.ConclusionsIn this experimental set-up, aortic stiffness increased significantly after stent graft deployment with each of the four types of stent graft, with the increase in aortic stiffness depending on the extent of stent graft coverage.

Toward the Virtual Benchmarking of Pneumatic Ventricular Assist Devices: Application of a Novel Fluid-Structure Interaction-Based Strategy to the Penn State 12 cc Device.

The pediatric use of pneumatic ventricular assist devices (VADs) as a bridge to heart transplant still suffers for short-term major complications such as bleeding and thromboembolism. Although numerical techniques are increasingly exploited to support the process of device optimization, an effective virtual benchmark is still lacking. Focusing on the 12 cc Penn State pneumatic VAD, we developed a novel fluid-structure interaction (FSI) model able to capture the device functioning, reproducing the mechanical interplay between the diaphragm, the blood chamber, and the pneumatic actuation. The FSI model included the diaphragm mechanical response from uniaxial tensile tests, realistic VAD pressure operative conditions from a dedicated mock loop system, and the behavior of VAD valves. Our FSI-based benchmark effectively captured the complexity of the diaphragm dynamics. During diastole, the initial slow diaphragm retraction in the air chamber was followed by a more rapid phase; asymmetries were noticed in the diaphragm configuration during its systolic inflation in the blood chamber. The FSI model also captured the major features of the device fluid dynamics. In particular, during diastole, a rotational wall washing pattern is promoted by the penetrating inlet jet with a low-velocity region located in the center of the device. Our numerical analysis of the 12 cc Penn State VAD points out the potential of the proposed FSI approach well resembling previous experimental evidences; if further tested and validated, it could be exploited as a virtual benchmark to deepen VAD-related complications and to support the ongoing optimization of pediatric devices.

Twelve Hours In Vitro Biocompatibility Testing of Membrane Oxygenators.

In vitro test systems for extracorporeal membrane oxygenation (mock loop) represent an interesting alternative to complex and expensive in vivo test systems to analyze the pathomechanisms leading to insufficient biocompatibility. Data on mock loop systems are limited, and operation times are constricted to a maximum duration of 6 hr. This study aims at a 12 hr operation time and frequent monitoring of markers for insufficient biocompatibility in two experimental settings. Porcine blood circulated in a mock loop without any modifications, or the circuit was operated with a CO2-enhanced gas (5% CO2/21% O2/74% N2) in combination with a nutrient solution (phosphate-adenine-glucose-guanosine-saline-mannitol). Coagulation parameters changed over time without differences between the two groups. In the unmodified test setting, a pH increase was detected after 1 hr, followed by significantly increased levels of free hemoglobin as a marker for hemolysis and elevated numbers of activated platelets, which correlate with detected von Willebrand factor, microparticles, and interleukin-β. Proinflammatory cytokine levels were significantly increased after 12 hr. In contrast, these parameters remained constant in the modified test setting providing proof of a stable operating in vitro mock loop system with an extended/prolonged operation time.

Centrifugal Blood Pump for Temporary Ventricular Assist Devices With Low Priming and Ceramic Bearings

A new model of centrifugal blood pump for temporary ventricular assist devices has been developed and evaluated. The design of the device is based on centrifugal pumping principles and the usage of ceramic bearings, resulting in a pump with reduced priming (35 ± 2 mL) that can be applied for up to 30 days. Computational fluid dynamic (CFD) analysis is an efficient tool to optimize flow path geometry, maximize hydraulic performance, and minimize shear stress, consequently decreasing hemolysis. Initial studies were conducted by analyzing flow behavior with different impellers, aiming to determine the best impeller design. After CFD studies, rapid prototyping technology was used for production of pump prototypes with three different impellers. In vitro experiments were performed with those prototypes, using a mock loop system composed of Tygon tubes, oxygenator, digital flow meter, pressure monitor, electronic driver, and adjustable clamp for flow control, filled with a solution (1/3 water, 1/3 glycerin, 1/3 alcohol) simulating blood viscosity and density. Flow-versus-pressure curves were obtained for rotational speeds of 1000, 1500, 2000, 2500, and 3000 rpm. As the next step, the CFD analysis and hydrodynamic performance results will be compared with the results of flow visualization studies and hemolysis tests.

Inertance Estimation in a Lumped-Parameter Hydraulic Simulator of Human Circulation

Pulsatile mock loop systems are largely used to investigate the cardiovascular system in vitro. They consist of a pump, which replicates the heart, coupled with a lumped-parameter hydraulic afterload, which simulates vasculature. An accurate dimensioning of components is required for a reliable mimicking of the physiopathological behavior of the system. However, it is not possible to create a component for the afterload inertance, and inertance contributions are present in the entire circuit. Hence, in the literature, inertance is neglected or qualitatively evaluated. In this paper, we propose two quantitative methods (Maximum-likelihood estimation (MLE) and Bayesian estimation) for estimating afterload inertance based on observed pressure and flow waveforms. These methods are also applied to a real mock loop system. Results show that the system has an inertance comparable with the literature reference value of the entire systemic circulation, and that the expected variations over inlet average flow and pulse frequency are in general confirmed. Comparing the methods, the Bayesian approach results in higher and more stable estimations than the classical MLE.

A New Model of Centrifugal Blood Pump for Cardiopulmonary Bypass: Design Improvement, Performance, and Hemolysis Tests

A new model of blood pump for cardiopulmonary bypass (CPB) application has been developed and evaluated in our laboratories. Inside the pump housing is a spiral impeller that is conically shaped and has threads on its surface. Worm gears provide an axial motion of the blood column. Rotational motion of the conical shape generates a centrifugal pumping effect and improves pumping performance. One annular magnet with six poles is inside the impeller, providing magnetic coupling to a brushless direct current motor. In order to study the pumping performance, a mock loop system was assembled. Mock loop was composed of Tygon tubes (Saint-Gobain Corporation, Courbevoie, France), oxygenator, digital flowmeter, pressure monitor, electronic driver, and adjustable clamp for flow control. Experiments were performed on six prototypes with small differences in their design. Each prototype was tested and flow and pressure data were obtained for rotational speed of 1000, 1500, 2000, 2500, and 3000 rpm. Hemolysis was studied using pumps with different internal gap sizes (1.35, 1.45, 1.55, and 1.7 mm). Hemolysis tests simulated CPB application with flow rate of 5 L/min against total pressure head of 350 mm Hg. The results from six prototypes were satisfactory, compared to the results from the literature. However, prototype #6 showed the best results. Best hemolysis results were observed with a gap of 1.45 mm, and showed a normalized index of hemolysis of 0.013 g/100 L. When combined, axial and centrifugal pumping principles produce better hydrodynamic performance without increasing hemolysis.

A New Pulsatile Volumetric Device With Biomorphic Valves for the In Vitro Study of the Cardiovascular System

A pulsatile mock loop system was designed and tested. This prototype represents a versatile, adjustable, and controllable experimental apparatus for in vitro studies of devices meant to interface with the human circulatory system. The pumping system consisted of a ventricular chamber featuring two biomorphic silicone valves as the inlet and outlet valves. The chamber volume is forced by a piston pump moved by a computer-controlled, low-inertia motor. Fluid dynamic tests with the device were performed to simulate physiological conditions in terms of cardiac output (mean flow of 5 and 6 L/min, with beat rates from 60 to 80 bpm), of rheological properties of the processed fluid, and of systemic circulation impedance. The pulsating actuator performed a good replication of the physiological ventricular behavior and was able to guarantee easy control of the waveform parameters. Experimental pressure and flow tracings reliably simulated the physiological profiles, and no hemolytic subatmospheric pressures were revealed. The performance of the prototype valves was also studied in terms of dynamic and static backflow, effective orifice area, and pressure loss, resulting in their applicability for this device. Mechanical reliability was also tested over 8 h. The device proved to be a reliable lab apparatus for in vitro tests; the pumping system also represents a first step toward a possible future application of pulsating perfusion in the clinic arena, such as in short-term cardiac assist and pulsatile cardiopulmonary bypass.

Hydraulic Bench Testing of the TruCATHTM/TruCCOMTMContinuous Cardiac Output Monitor

The aim of this study was to test the truCATHTM/ truCOMMSTM continuous cardiac output catheter/monitor in a computer-controlled pulsatile mock loop system. The pulmonary artery catheter is equipped with two thermistors and a heating coil which maintains a 2°C temperature difference between the thermistors. The required electrical power is assumed to be an indicator of cardiac output. The catheter was tested under a variety of loading conditions including changes in heart rate (60, 75, 90, 120 beats/mm), filling pressures (0–15 mmHg), ventricular driving pressures (22–135 mmHg), and pulmonary resistance (0.08–1.47 mmHg⋅s/mL) in random combinations, generating flows of 1.5–10 L/min. Fluid temperature was varied between 32 and 42°C. Our data demonstrate a good linear relation between the electrical power output of the TruCATHTM/TruCOMMSTM catheter and the actual flow as measured volumetrically. The system appeared to be sensitive to fluid temperature changes, but dimensionless analysis with Womersley and Reynolds numbers revealed that it is a direct consequence of the temperature-dependent water viscosity. We conclude that the TruCATHTM/TruCOMMSTM is a potentially useful clinical tool but the absolute correspondence between the catheter output and the patient's actual cardiac output remains to be assessed.

Endurance test on a textured diaphragm for the auxiliary total artificial heart (ATAH).

We performed an endurance test on a textured diaphragm made of polyurethane (BioSpan, The Polymer Technology Group, San Francisco, CA, U.S.A.) to be used in the auxiliary total artificial heart (ATAH), an electromechanical device that can be totally implantable without removing the natural heart due to the device's reduced dimension. The objective of this endurance test was to predict whether this diaphragm would be capable of resisting in vivo tests with the ATAH implanted for fifteen days in calves. In this study, a mock loop system simulating the human circulatory system was used. The test protocol was elaborated to reproduce extreme physiological conditions. The technique to produce the textured diaphragms made of polyurethane is shown. The textured surface is used as basis to fix a layer of calf-skin gelatin. The technique used to make the diaphragm guaranteed a totally textured surface without cracking. The diaphragm demonstrated enough resistance to be used at the 15 day in vivo experiments.

Mock loop testing of On-x prosthetic mitral valve with Doppler echocardiography.

Previous in vitro testing (mainly in aortic position) and clinical experience (often based on Doppler echocardiographic observations) demonstrated an excellent hemodynamic behavior of the On-X valve. However, integrative studies including simultaneous hemodynamic pressure and flow measurements and Doppler echocardiography are lacking. Using our computer-controlled mock loop system, two samples of the Mitral 27/29 and one sample of the Conform-X Mitral 25/33 are tested in mitral position. Data include transvalvular pressure gradient and flow as well as transthoracic Doppler echocardiography. The valves are tested under three pressure conditions (ventricular systolic pressure of 100, 130, and 160 mm Hg) at three different heart rates (60, 100, and 140 beats/min). In addition, ventricular pressure conditions simulating fibrillation are imposed. Both valve types show similar hydrodynamic characteristics and have an effective orifice area of 2.1 cm2 and a performance index of 0.56 for a cardiac output of 3.5 L/min. Regurgitant volumes remain below 6 ml.