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More than 13 million children are born preterm annually. Prematurity-related mortality accounts for 0.9 million deaths worldwide. The majority of those affected are Extremely Preterm Infants (gestational age less than 28 weeks). Immaturity causes organ failure and specific morbidities like germinal matrix hemorrhage, bronchopulmonary dysplasia, and necrotizing enterocolitis. Artificial womb and placenta technologies address these issues. As a bridge-to-life technology, they provide a liquid environment to allow organ maturation under more physiological conditions. The proposed artificial womb can adapt to fetal growth. Volume adjustment is achieved by removing fluid from the interspace between an inner and outer chamber. Results of the in vitro tests showed a temperature constancy of 36.8°C ± 0.3°C without pressure loss over 7 days. The volume of the inner sac was variable between 3.6 and 7.0 L. We designed a filtration and disinfection system for this particular purpose. This system has proven strong disinfection capabilities, effective filtering of metabolic waste, and the ability to avoid phospholipid washout. The presented artificial womb has sufficient volume variability to adapt to the physiologic growth of an extremely preterm neonate over a 4-week period. We regard this as an important step in the development of this bridge-to-life technology.
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Órganos Artificiales , Recien Nacido Extremadamente Prematuro , Humanos , Recién Nacido , Femenino , Embarazo , Desinfección , Edad GestacionalRESUMEN
BACKGROUND: In the total artificial heart (TAH), the inputs to the physiological control unit, preload, and afterload, are detected from intrinsic pump parameters (e.g., motor current). Within this study, their detection techniques are developed, and their reliability in pre- and afterload prediction is mapped for a broad range of cardiovascular system states. METHODS: We used ReinHeart TAH which is a fully implantable TAH with a plunger coil drive that is alternately emptying the left and right chambers. From the coil currents we first derived a force generated by the piston with respect to its position and then analyzed its pattern to detect (1) preload-chamber filling, found as piston position at begin ejection and (2) afterload-mean outflow pressures, determined as linearly calibrated average piston force during ejection. TAH is then integrated into a mock loop circulation (MLC) which is set to 135 different steady operating points varying in chamber filling (0%-100%, five steps), mean outflow pressures (system circulation: 60-90-120 mm Hg, pulmonary circulation: 15-30-45 mm Hg), and heart cycle duration (171-600 ms in seven non-equidistant steps). The detected preload and afterload are compared to MLC set values, and the errors are mapped. RESULTS: Respectively for the left and right chambers, the preload was detectable in 134 and 118 operating points and the mean error was ±3% and ±2%. The afterload was detectable in 135 and 87 operating points and the mean error was 37% and 30% respectively for left and right circulation. The operational points that are further away from homeostatic equilibrium values generally yielded larger errors. The largest errors were observed for right circulation at long cycle duration, low afterload, and low filling. CONCLUSIONS: The study yields reliable preload estimation in a broad range of physiological states, particularly for left circulation. Detection of afterload needs further improvements. The study revealed a need for piston movement optimization within the ReinHeart TAH during the early phase of systole.
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Corazón Artificial , Corazón , Reproducibilidad de los Resultados , Sístole , Circulación PulmonarRESUMEN
The objective of this study is to identify the preload and afterload sensitivity of the ReinHeart TAH 2.0. For adequate left-right flow balance, the concept of a reduced right stroke volume (by about 10%) and active adaption of the right diastole duration are evaluated concerning the controllability of the flow balance. This study used an active mock circulation loop to test a wide range of preload and afterload conditions. Preload sensitivity was tested at atrial pressures (APs) between 4 and 20 mm Hg. Left afterload was varied in a range of 60-140 mm Hg mean aortic pressure (MAP), right afterload was simulated between 15 and 40 mm Hg. Four scenarios were developed to verify that the flow difference fully covers the defined target range of 0-1.5 L/min. Although a positive correlation between inlet pressure and flow is identified for the right pump chamber, the left pump chamber already fills completely at an inlet pressure of 8-10 mm Hg. With increasing afterload, both the left and right flow decrease. A positive flow balance (left flow exceeds right flow) is achieved over the full range of tested afterloads. At high APs, the flow difference is limited to a maximum of 0.7 L/min. The controllability of flow balance was successfully evaluated in four scenarios, revealing that a positive flow difference can be achieved over the full range of MAPs. Under physiological test conditions, the linear relationship between flow and heart rate was confirmed, ensuring good controllability of the TAH.
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Circulación Sanguínea , Corazón Artificial , Diseño de Prótesis , Presión Sanguínea , Frecuencia Cardíaca , Hidrodinámica , Modelos CardiovascularesRESUMEN
BACKGROUND: Membranes based on triply periodic minimal surfaces (TPMS) have proven a superior gas transfer compared to the contemporary hollow fiber membrane (HFM) design in artificial lungs. The improved oxygen transfer is attributed to disrupting the laminar boundary layer adjacent to the membrane surface known as main limiting factor to mass transport. However, it requires experimental proof that this improvement is not at the expense of greater damage to the blood. Hence, the aim of this work is a valid statement regarding the structure-dependent hemolytic behavior of TPMS structures compared to the current HFM design. METHODS: Hemolysis tests were performed on structure samples of three different kind of TPMS-based designs (Schwarz-P, Schwarz-D and Schoen's Gyroid) in direct comparison to a hollow fiber structure as reference. RESULTS: The results of this study suggest that the difference in hemolysis between TPMS membranes compared to HFMs is small although slightly increased for the TPMS membranes. There is no significant difference between the TPMS structures and the hollow fiber design. Nevertheless, the ratio between the achieved additional oxygen transfer and the additional hemolysis favors the TPMS-based membrane shapes. CONCLUSION: TPMS-shaped membranes offer a safe way to improve gas transfer in artificial lungs.
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Órganos Artificiales , Hemólisis , Pulmón , Membranas Artificiales , Diseño de Equipo , Humanos , Impresión TridimensionalRESUMEN
An in-vitro study was conducted to investigate the general feasibility of using only one pumping chamber of the SynCardia total artificial heart (TAH) as a replacement of the single ventricle palliated by Fontan circulation. A mock circulation loop was used to mimic a Fontan circulation. The combination of both ventricle sizes (50 and 70 cc) and driver (Freedom Driver and Companion C2 Driver) was investigated. Two clinical relevant scenarios (early Fontan; late Fontan) as derived from literature data were set up in the mock loop. The impact of increased transpulmonary pressure gradient, low atrial pressure, and raised central venous pressure on cardiac output was studied. From a hemodynamic point, the single-chambered TAH performed sufficiently in the setting of the Fontan circulation. Increased transpulmonary pressure gradient, from ideal to pulmonary hypertension, decreased the blood flow in combinations by almost 2 L/min. In the early Fontan scenario, a cardiac output of 3-3.5 L/min was achieved using the 50 cc ventricle, driven by the Companion C2 Driver. Even under pulmonary hypertension, cardiac outputs greater than 4 L/min could be obtained with the 70 cc pump chamber in the late Fontan scenario. In the clinically relevant Fontan scenarios, implementation of the single chambered TAH performed successfully from a hemodynamic point of view. The replacement of the failing univentricular heart by a single chamber of the SynCardia TAH may provide an alternative to a complex biventricular repair procedure or ventricular support in Fontan patients.
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Procedimiento de Fontan , Cardiopatías Congénitas , Corazón Artificial , Gasto Cardíaco , Procedimiento de Fontan/métodos , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/cirugía , Ventrículos Cardíacos/cirugía , Hemodinámica/fisiología , HumanosRESUMEN
Transcatheter aortic valve replacement (TAVR) has emerged as a widely used therapy for aortic valve diseases. With TAVR, flow hemodynamics may change leading to areas of flow stagnation prone to thrombosis risk. The neo-sinus, created by introducing a prosthesis inside the diseased native valve, may prompt leaflet thrombosis due to areas of flow stasis. This study attempted to understand the effect of different prosthesis implant depths on the flow field within the neo- and native sinus and on the coronary perfusion. Experiments were performed inside an in vitro pulse duplicator producing physiological conditions according to ISO 5840-1:2015 standard. Flow fields were obtained for two cardiac outputs (CO) using particle image velocimetry (PIV). Washout was calculated as a measure of flow stasis. The two main results are: a lower implant position and a lower CO/frequency led to better native sinus washout, but worsened neo-sinus washout. In contrast, a higher implant position led to higher coronary flow (for higher CO/frequency). No significant effect of implant depth on coronary flow was observed for lower CO/frequency. In summary, a higher implant position using this self-expanding prosthesis is associated with reduced neo-sinus flow stasis. Hereby, washout of the native sinus, as well as coronary flow, are dependent on cardiac output.
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Estenosis de la Válvula Aórtica/cirugía , Prótesis Valvulares Cardíacas/efectos adversos , Modelos Cardiovasculares , Diseño de Prótesis , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Válvula Aórtica/fisiopatología , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/fisiopatología , Velocidad del Flujo Sanguíneo , Gasto Cardíaco , Circulación Coronaria , Humanos , Reología , Reemplazo de la Válvula Aórtica Transcatéter/métodos , Resultado del TratamientoRESUMEN
Thrombogenic complications are a main issue in mechanical circulatory support (MCS). There is no validated in vitro method available to quantitatively assess the thrombogenic performance of pulsatile MCS devices under realistic hemodynamic conditions. The aim of this study is to propose a method to evaluate the thrombogenic potential of new designs without the use of complex in-vivo trials. This study presents a novel in vitro method for reproducible thrombogenicity testing of pulsatile MCS systems using low molecular weight heparinized porcine blood. Blood parameters are continuously measured with full blood thromboelastometry (ROTEM; EXTEM, FIBTEM and a custom-made analysis HEPNATEM). Thrombus formation is optically observed after four hours of testing. The results of three experiments are presented each with two parallel loops. The area of thrombus formation inside the MCS device was reproducible. The implantation of a filter inside the loop catches embolizing thrombi without a measurable increase of platelet activation, allowing conclusions of the place of origin of thrombi inside the device. EXTEM and FIBTEM parameters such as clotting velocity (α) and maximum clot firmness (MCF) show a total decrease by around 6% with a characteristic kink after 180 minutes. HEPNATEM α and MCF rise within the first 180 minutes indicate a continuously increasing activation level of coagulation. After 180 minutes, the consumption of clotting factors prevails, resulting in a decrease of α and MCF. With the designed mock loop and the presented protocol we are able to identify thrombogenic hot spots inside a pulsatile pump and characterize their thrombogenic potential.
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Corazón Artificial/efectos adversos , Tromboelastografía/instrumentación , Trombosis/etiología , Animales , Diseño de Equipo , Porcinos/sangre , Tromboelastografía/métodosRESUMEN
A total artificial heart (TAH) must be designed to autonomously balance the flows of the systemic and pulmonary circulation to prevent potentially lethal lung damage. The flow difference between the systemic and pulmonary circulation is mainly caused by the bronchial (arteries) shunt flow and can change dynamically. The ReinHeart TAH consists of only one actuator that ejects blood alternately from the right and left pump chamber. This design entails a coupling of the right and left stroke and thus, complicates the independent adaptation of the right and left flow. In this experimental study on the ReinHeart TAH, four concepts to keep the flows well balanced were investigated using an active mock circulation loop for data acquisition. Three concepts are based on mechanical design changes (variation of pusher plate shape, flexible right pump chamber housing, and reduced right stroke volume) to achieve a static flow difference. In combination with these static concepts, a concept influencing the ratio of systole and diastole duration to respond to dynamic changes was studied. In total, four measurement series, each with 270 operating points, to investigate the influence of circulatory filling volume, heart rate, bronchial shunt flow, and lung resistance were recorded. In the course of this study, we introduce a concept deviation indicator, providing information about the efficiency of the concepts to balance the flows based on changes in lung's blood pressures. Furthermore, the distribution of the measured data was evaluated based on bubble plot visualizations. The investigated variation of the right pusher plate shape results in high lung pressures which will cause lethal lung damage. In comparison, a flexible right pump chamber housing shows lower lung pressures, but it still has the potential to damage the lungs. Reducing the stroke volume of the right pump chamber results in proper lung pressures. The flow balance can dynamically be influenced with a positive effect on the lung pressures by choosing a suitable systole-diastole-ratio. The results of this study suggest that an adequate right-left flow balance can be achieved by combining the mechanical concept of a reduced right stroke volume with an active control of the systole-diastole-ratio.
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Corazón Artificial , Modelos Cardiovasculares , Diseño de Prótesis , Circulación Pulmonar/fisiología , Presión Sanguínea/fisiología , Arterias Bronquiales/fisiología , Diástole/fisiología , Frecuencia Cardíaca/fisiología , Humanos , Volumen Sistólico/fisiología , Sístole/fisiologíaRESUMEN
Spatially resolved measurement of blood flow is of great interest in the development of artificial blood-carrying devices such as blood pumps, heart valve prostheses, and oxygenators. Particle image velocimetry (PIV) is able to measure instantaneous velocity fields in a plane with high accuracy and is being used more frequently for the development of such devices. However, as this measurement technique is based on optical access, blood flow at physiological hematocrit values is difficult to measure due to its low transparency and multiscattering properties. So far, only very small dimensions (in the range of 400 µm) can be measured using PIV. A suspension of ghost cells (GCs) offers a higher optical transparency than blood while having a similar rheological behavior. In this study, a procedure for the production of GC suspensions containing a very low intracellular hemoglobin concentration is presented. With the help of multiple rounds of controlled cell lysis, the intracellular hemoglobin concentration could be decreased to a point where a standard macroscopic PIV measurement was possible. A velocity profile of a 44% GC suspension in a circular channel with a diameter of 9.5 mm was measured with high spatial resolution. Meanwhile, the rheological behavior was found to be comparable with blood.
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Eritrocitos/citología , Reología/métodos , Animales , Hemólisis , Hemorreología , PorcinosRESUMEN
Even though the separation of blood into erythrocyte-rich and erythrocyte-poor areas is well known in physiological setups such as small vessels, it has recently come into focus in small gaps in cardiovascular applications. Studies show that separation effects occur, for example, in gaps in hydrodynamic bearings, where they can have a positive effect on hemolysis. Separation effects depend on the hematocrit value, but due to visualization issues, studies in small gaps used very low hematocrit values. In this study, a test setup and an evaluation method for the investigation of separation effects of blood with hematocrit values of 30, 45, and 60% were developed. The erythrocyte distribution was evaluated by means of gray scale value distribution. This principle is based on the fact that an erythrocyte-rich region is more opaque than an erythrocyte-poor region. The experimental setup is designed in a way that no further processes (e.g., fluorescence labeling) need to be carried out which might change the properties of the membrane of the erythrocytes, and therefore their flow properties. Additionally, the method is executable with basic laboratory equipment, which makes it applicable for many laboratories. To validate the feasibility of the method, the influence of the diameter and the flow rate on the migration of erythrocytes were studied in micro channels for three different physiological hematocrit values. Even though no individual cells were traced, plasma layer and areas of high erythrocyte concentration could be identified. Dependencies of the erythrocyte distribution on flow rate and channel diameter were validated. The influence of the hematocrit value was demonstrated as well and showed the hematocrit value to be a crucial factor when investigating cell separation. The experimental results were consistent with findings in the literature. As the developed method is suitable for physiological hematocrit values and easy to handle, it provides an optimal basis for cell separation studies in gap models with whole blood, for example, hydrodynamic bearings, where it can be used to optimize these devices.
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Eritrocitos/citología , Hematócrito , Hemorreología , Animales , Velocidad del Flujo Sanguíneo , Viscosidad Sanguínea , Diseño de Equipo , Hidrodinámica , Dispositivos Laboratorio en un Chip , PorcinosRESUMEN
Rotary blood pumps in Extracorporeal Life Support (ECLS) applications are optimized for a specific design point. However, in clinical practice, these pumps are usually applied over a wide range of operation points. Studies have shown that a deviation from the design point in a rotary blood pump leads to an unexpected rise of hemolysis with corresponding clinical complications. Adjustable pumps that can adapt geometric parameters to the respective operation point are commonly used in other industrial branches, but yet not applied in blood pumps. We present a novel mechanism to adjust the impeller geometry of a centrifugal blood pump during operation together with in-vitro data of its hydraulic performance and efficiency. Three-dimensionalprinted prototypes of the adjustable impeller and a rigid impeller were manufactured and hydraulic performance and efficiency measured (n = 3). In a flow range of 1.5-9.5 L/min, the adjustable pump increased pump performance up to 47% and hydraulic efficiency by an average of 7.3 percentage points compared with a fixed setting. The adjustable pump allows customization of the pump's behavior (steepness of performance curve) according to individual needs. Furthermore, the hydraulic efficiency of the pump could be maintained at a high level throughout the complete flow range.
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Corazón Auxiliar , Humanos , Diseño de Equipo , HemólisisRESUMEN
High intensity noise exposure leads to a permanent shift in auditory thresholds (PTS), affecting both peripheral (cochlear) tissue and the central auditory system. Studies have shown that a noise-induced hearing loss results in significant cell loss in several auditory structures. Degeneration can be demonstrated within hours after noise exposure, particularly in the lower auditory pathway, and continues to progress over days and weeks following the trauma. However, there is limited knowledge about the effects of recurring acoustic trauma. Repeated noise exposure has been demonstrated to increase neuroplasticity and neural activity. Thus, the present study aimed to investigate the influence of a second noise exposure on the cytoarchitecture of key structures of the auditory pathway, including spiral ganglion neurons (SGN), the ventral and dorsal cochlear nucleus (VCN and DCN, respectively), and the inferior colliculus (IC). In the experiments, young adult normal hearing mice were exposed to noise once or twice (with the second trauma applied one week after the initial exposure) for 3 h, using broadband white noise (5 - 20 kHz) at 115 dB SPL. The cell densities in the investigated auditory structures significantly decreased in response to the initial noise exposure compared to unexposed control animals. These findings are consistent with earlier research, which demonstrated degeneration in the auditory pathway within the first week after acoustic trauma. Additionally, cell densities were significantly decreased after the second trauma, but this effect was only observed in the VCN, with no similar effects seen in the SGN, DCN, or IC. These results illustrate how repeated noise exposure influences the cytoarchitecture of the auditory system. It appears that an initial noise exposure primarily damages the lower auditory pathway, but surviving cellular structures may develop resistance to additional noise-induced injury.
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Pérdida Auditiva Provocada por Ruido , Colículos Inferiores , Ratones , Animales , Vías Auditivas , Pérdida Auditiva Provocada por Ruido/metabolismo , Ruido/efectos adversos , Cóclea/metabolismo , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico , Estimulación AcústicaRESUMEN
The overall survival rate of extracorporeal life support (ECLS) remains at 60%. Research and development has been slow, in part due to the lack of sophisticated experimental models. This publication introduces a dedicated rodent oxygenator ("RatOx") and presents preliminary in vitro classification tests. The RatOx has an adaptable fiber module size for various rodent models. Gas transfer performances over the fiber module for different blood flows and fiber module sizes were tested according to DIN EN ISO 7199. At the maximum possible amount of effective fiber surface area and a blood flow of 100 mL/min, the oxygenator performance was tested to a maximum of 6.27 mL O2/min and 8.2 mL CO2/min, respectively. The priming volume for the largest fiber module is 5.4 mL, while the smallest possible configuration with a single fiber mat layer has a priming volume of 1.1 mL. The novel RatOx ECLS system has been evaluated in vitro and has demonstrated a high degree of compliance with all pre-defined functional criteria for rodent-sized animal models. We intend for the RatOx to become a standard testing platform for scientific studies on ECLS therapy and technology.
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Several studies highlight the importance of the order of different instructional methods when designing learning environments. Correct but also erroneous worked examples are frequently used methods to foster students' learning performance, especially in problem-solving. However, so far no study examined how the order of these example types affects learning. While the expertise reversal effect would suggest presenting correct examples first, the productive failure approach hypothesizes the reversed order to be learning-facilitating. In addition, congruency of subsequent exemplified problems was tested as a moderator of the effect of order on learning. For example, with arithmetic tasks, congruent problems target exactly the same calculation while incongruent problems refer to different calculations. Following cascade theory, a model of cognitive skill acquisition, presenting correct examples first should be more effective when the subsequent exemplified problems are different. To test the (conflicting) hypotheses, 83 university students were assigned to one of the four conditions in a 2 (correct vs. erroneous example first) × 2 (same vs. different exemplified problems) between-subject design. Learners navigated through a slideshow on the topic of Vedic mathematics consisting of explicit instruction, worked examples differing in terms of the experimental condition, and transfer problems. Although no main or interaction effects were found regarding students' learning performance, mediational analysis offered support for the expertise reversal effect, as it indicated that there is a significant indirect effect of order via mental load on learning. Presenting correct examples first and erroneous examples second resulted in a lower mental load, which in turn was associated with better learning performance. In contrast, presenting erroneous examples first and correct examples second resulted in a more accurate self-assessment of learning performance. These findings offer first insights into the question of how the presentation order of different example types impacts learning and provide practical recommendations for the design of educational media. Results are discussed in light of the ongoing debate regarding the question if less guided instructional methods should precede or succeed more guided methods.
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A downsized version of the ReinHeart total artificial heart (TAH) was developed. Hemocompatibility needs to be revised since the operating point of the downsized TAH has changed to a higher pump frequency to accomplish the same cardiac output. A mock circulation loop was designed, containing a left side for hemocompatibility testing and a right side to mimic realistic work conditions. A protocol for hemolysis testing was established using pooled porcine blood with an operation point of 5 L/min, a mean outlet pressure of 100 mm Hg and a mean inlet pressure of 12 mm Hg. Six trials were performed testing two downsized TAH (one with a compliance chamber [CC] connected, necessary for a pneumatic decoupling of both membranes and one open to atmosphere) and a BPX-80 as reference pump. The average modified index of hemolysis and normalized index of hemolysis (NIH in mg/100L) from six individual trials of the reference pump were 0.34 (0.07) and 3.21 (0.61) and of the TAH open to atmosphere 4.18 (1.19) and 38.85 (10.59), respectively. In between TAH with and without CC, there was no significant difference. A NIH ratio of TAH and reference pump was calculated to minimize variation of the different blood batches used in individual trials. Due to the downsizing, the ReinHeart's hemolysis level increased by around 22% compared with the original size version. Comparing the results to clinically approved left ventricular assist devices, the level of hemolysis can still be considered acceptable.
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Corazón Artificial , Corazón Auxiliar , Animales , Gasto Cardíaco , Corazón Artificial/efectos adversos , Corazón Auxiliar/efectos adversos , Hemólisis , Diseño de Prótesis , PorcinosRESUMEN
Membrane lungs consist of thousands of hollow fiber membranes packed together as a bundle. The devices often suffer from complications because of non-uniform flow through the membrane bundle, including regions of both excessively high flow and stagnant flow. Here, we present a proof-of-concept design for a membrane lung containing a membrane module based on triply periodic minimal surfaces (TPMS). By warping the original TPMS geometries, the local permeability within any region of the module could be raised or lowered, allowing for the tailoring of the blood flow distribution through the device. By creating an iterative optimization scheme for determining the distribution of streamwise permeability inside a computational porous domain, the desired form of a lattice of TPMS elements was determined via simulation. This desired form was translated into a computer-aided design (CAD) model for a prototype device. The device was then produced via additive manufacturing in order to test the novel design against an industry-standard predicate device. Flow distribution was verifiably homogenized and residence time reduced, promising a more efficient performance and increased resistance to thrombosis. This work shows the promising extent to which TPMS can serve as a new building block for exchange processes in medical devices.
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Pulmón , Simulación por Computador , Membranas , Permeabilidad , PorosidadRESUMEN
Extracorporeal membrane oxygenation (ECMO) is an established rescue therapy for patients with chronic respiratory failure waiting for lung transplantation (LTx). The therapy inherent immobilization may result in fatigue, consecutive deteriorated prognosis, and even lost eligibility for transplantation. We conducted a feasibility study on a novel system designed for the deployment of a portable ECMO device, enabling the physical exercise of awake patients prior to LTx. The system comprises a novel oxygenator with a directly connected blood pump, a double-lumen cannula, gas blender and supply, as well as control and energy management. In vitro experiments included tests regarding performance, efficiency, and blood damage. A reduced system was tested in vivo for feasibility using a novel large animal model. Six anesthetized pigs were first positioned in supine position, followed by a 45° angle, simulating an upright position of the patients. We monitored performance and vital parameters. All in vitro experiments showed good performance for the respective subsystems and the integrated system. The acute in vivo trials of 8 h duration confirmed the results. The novel portable ECMO-system enables adequate oxygenation and decarboxylation sufficient for, e.g., the physical exercise of designated LTx-recipients. These results are promising and suggest further preclinical studies on safety and efficacy to facilitate translation into clinical application.
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Tip geometry and placement of rotary blood pump inflow and outflow cannulae influence the dynamics of flow within the ventricle and aortic branch. Cannulation, therefore, directly influences the potential for thrombus formation and end-organ perfusion during ventricular assist device (VAD) support or cardiopulmonary bypass (CPB). The purpose of this study was to investigate the effect of various inflow/outflow cannula tip geometries and positions on ventricular and greater vessel flow patterns to evaluate ventricular washout and impact on cerebral perfusion. Transparent models of a dilated cardiomyopathic ventricle and an aortic branch were reconstructed from magnetic resonance imaging data to allow flow measurements using particle image velocimetry (PIV). The contractile function of the failing ventricle was reproduced pneumatically, and supported with a rotary pump. Flow patterns were visualized around VAD inflow cannulae, with various tip geometries placed in three positions in the ventricle. The outflow cannula was placed in the subclavian artery and at several positions in the aorta. Flow patterns were measured using PIV and used to validate an aortic flow computational fluid dynamic study. The PIV technique indicated that locating the inflow tip in the left ventricular outflow tract improved complete ventricular washout while the tip geometry had a smaller influence. However, side holes in the inflow cannula improved washout in all cases. The PIV results confirmed that the positioning and orientation of the outflow cannula in the aortic branch had a high impact on the flow pattern in the vessels, with a negative blood flow in the right carotid artery observed in some cases. Cannula placement within the ventricle had a high influence on chamber washout. The positioning of the outflow cannula directly influences the flow through the greater vessels, and may be responsible for the occasional reduction in cerebral perfusion seen in clinical CPB.
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Aorta/fisiología , Cateterismo/instrumentación , Corazón Auxiliar , Hemodinámica , Animales , Aorta/anatomía & histología , Diseño de Equipo , Humanos , Modelos Cardiovasculares , Arteria Subclavia/fisiología , PorcinosRESUMEN
OBJECTIVES: In recent years, cochlear implants have been applied successfully for the treatment of unilateral hearing loss with quite surprising benefit. One reason for this successful treatment, including the relief from tinnitus, could be the normalization of spontaneous activity in the central auditory pathway because of the electrical stimulation. The present study, therefore, investigated at a cellular level, the effect of a unilateral chronic intracochlear stimulation on key structures of the central auditory pathway. DESIGN: Normal-hearing guinea pigs were mechanically single-sided deafened through a standard HiFocus1j electrode array (on a HiRes 90k cochlear implant) being inserted into the first turn of the cochlea. Four to five electrode contacts could be used for the stimulation. Six weeks after surgery, the speech processor (Auria) was fitted, based on tNRI values and mounted on the animal's back. The two experimental groups were stimulated 16âhours per day for 90 days, using a HiRes strategy based on different stimulation rates (low rate (275âpps/ch), high rate (5000âpps/ch)). The results were compared with those of unilateral deafened controls (implanted but not stimulated), as well as between the treatment groups. All animals experienced a standardized free field auditory environment. RESULTS: The low-rate group showed a significantly lower average spontaneous activity bilaterally in the dorsal cochlear nucleus and the medial geniculate body than the controls. However, there was no difference in the inferior colliculus and the primary auditory cortex. Spontaneous activity of the high-rate group was also reduced bilaterally in the dorsal cochlear nucleus and in the primary auditory cortex. No differences could be observed between the high-rate group and the controls in the contra-lateral inferior colliculus and medial geniculate body. The high-rate group showed bilaterally a higher activity in the CN and the MGB compared with the low-rate group, whereas in the IC and in the AC a trend for an opposite effect could be determined. CONCLUSIONS: Unilateral intracochlear electrical stimulation seems to facilitate the homeostasis of the network activity, since it decreases the spontaneous activity that is usually elevated upon deafferentiation. The electrical stimulation per se seems to be responsible for the bilateral changes described above, rather than the particular nature of the electrical stimulation (e.g., rate). The normalization effects of electrical stimulation found in the present study are of particular importance in cochlear implant recipients with single-sided deafness.
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Vías Auditivas/fisiopatología , Implantes Cocleares , Sordera/fisiopatología , Sordera/terapia , Lateralidad Funcional/fisiología , Animales , Animales Recién Nacidos , Corteza Auditiva/fisiopatología , Cóclea/fisiopatología , Implantación Coclear , Núcleo Coclear/fisiopatología , Modelos Animales de Enfermedad , CobayasRESUMEN
It is of the utmost importance to reduce flow-induced hemolysis in devices such as heart-valve prostheses and blood pumps. Thus, in vitro measurements of hemolysis are performed in order to optimize their design in this regard. However, with existing measurement methods, hemolysis can only be assessed as an integrated value over the complete test-circuit. Currently, there are no spatially-resolved in vitro hemolysis measurement techniques known to the authors that would allow for a determination of the critical regions within a device. In this study, a novel spatially-resolved measurement principle is proposed. Ghost cells (i.e. erythrocytes with a lower hemoglobin concentration) were loaded with a calcium-dicitrato complex, and a fluorescent calcium indicator was suspended in the extracellular medium. Calcium and indicator are separated until the cell membrane ruptures (i.e. hemolysis occurs). In the moment of hemolysis, the two compounds bind to each other and emit a fluorescent signal that can be recorded and spatially-resolved in a setup very similar to a standard Particle Image Velocimetry measurement. A proof-of-principle experiment was performed by intentionally inducing hemolysis in a flow-model with a surfactant. The surfactant-induced hemolysis demonstrated a clear increase of the fluorescent signal compared to that of a negative reference. Furthermore, the signal was spatially restricted to the area of hemolysis. Although further challenges need to be addressed, a successful proof-of-principle for novel spatially-resolved hemolysis detection is presented. This method can contribute to better design optimization of devices with respect to flow-induced hemolysis.