Ilona Mager

The Aachen MiniHLM—A Miniaturized Heart‐Lung Machine for Neonates With an Integrated Rotary Blood Pump

The operation of congenital heart defects in neonates often requires the use of heart-lung machines (HLMs) to provide perfusion and oxygenation. This is prevalently followed by serious complications inter alia caused by hemodilution and extrinsic blood contact surfaces. Thus, one goal of developing a HLM for neonates is the reduction of priming volume and contact surface. The currently available systems offer reasonable priming volumes for oxygenators, reservoirs, etc. However, the necessary tubing system contains the highest volumes within the whole system. This is due to the use of roller pumps; hence, the resulting placement of the complete HLM is between 1 and 2 m away from the operating table due to connective tubing between the components. Therefore, we pursued a novel approach for a miniaturized HLM (MiniHLM) by integrating all major system components in one single device. In particular, the MiniHLM is a HLM with the rotary blood pump centrically integrated into the oxygenator and a heat exchanger integrated into the cardiotomy reservoir which is directly connected to the pump inlet. Thus, tubing is only necessary between the patient and MiniHLM. A total priming volume of 102 mL (including arterial filter and a/v line) could be achieved. To validate the overall concept and the specific design we conducted several in vitro and in vivo test series. All tests confirm the novel concept of the MiniHLM. Its low priming volume and blood contact surface may significantly reduce known complications related to cardiopulmonary bypass in neonates (e.g., inflammatory reaction and capillary leak syndrome).

Micro-structuring of polycarbonate-urethane surfaces in order to reduce platelet activation and adhesion

In the development of new hemocompatible biomaterials, surface modification appears to be a suitable method in order to reduce the thrombogenetic potential of such materials. In this study, polycarbonate-urethane (PCU) tubes with different surface microstructures to be used for aortic heart valve models were investigated with regard to the thrombogenicity. The surface structures were produced by using a centrifugal casting process for manufacturing PCU tubes with defined casting mold surfaces which are conferred to the PCU surface during the process. Tubes with different structures defined by altering groove widths were cut into films and investigated under dynamic flow conditions in contact with porcine blood. The analysis was carried out by laser scanning microscopy which allowed for counting various morphological types of platelets with regard to the grade of activation. The comparison between plain and shaped PCU samples showed that the surface topography led to a decline of the activation of the coagulation cascade and thus to the reduction of the fibrin synthesis. Comparing different types of structures revealed that smooth structures with a small groove width (d ~ 3 μm) showed less platelet activation as well as less adhesion in contrast to a distinct wave structure (d ~ 90 μm). These results prove surface modification of polymer biomaterials to be a suitable method for reducing thrombogenicity and hence give reason for further alterations and improvements.

Mock Circulation Loop to Investigate Hemolysis in a Pulsatile Total Artificial Heart

Hemocompatibility of blood pumps is a crucial parameter that has to be ensured prior to in vivo testing. In contrast to rotary blood pumps, a standard for testing a pulsatile total artificial heart (TAH) has not yet been established. Therefore, a new mock circulation loop was designed to investigate hemolysis in the left ventricle of the ReinHeart TAH. Its main features are a high hemocompatibility, physiological conditions, a low priming volume, and the conduction of blood through a closed tubing system. The mock circulation loop consists of a noninvasive pressure chamber, an aortic compliance chamber, and an atrium directly connected to the ventricle. As a control pump, the clinically approved Medos-HIA ventricular assist device (VAD) was used. The pumps were operated at 120 beats per minute with an aortic pressure of 120 to 80 mm Hg and a mean atrial pressure of 10 mm Hg, generating an output flow of about 5 L/min. Heparinized porcine blood was used. A series of six identical tests were performed. A test method was established that is comparable to ASTM F 1841, which is standard practice for the assessment of hemolysis in continuous-flow blood pumps. The average normalized index of hemolysis (NIH) values of the VAD and the ReinHeart TAH were 0.018 g/100 L and 0.03 g/100 L, respectively. The standard deviation of the NIH was 0.0033 for the VAD and 0.0034 for the TAH. Furthermore, a single test with a BPX-80 Bio-Pump was performed to verify that the hemolysis induced by the mock circulation loop was negligible. The performed tests showed a good reproducibility and statistical significance. The mock circulation loop and test protocol developed in this study are valid methods to investigate the hemolysis induced by a pulsatile blood pump.

In vitro performance testing of a pediatric oxygenator with an integrated pulsatile pump.

For different lung and heart diseases (e.g., acute respiratory distress syndrome, congenital heart failure, and cardiomyopathy) extracorporeal membrane oxygenation is a well-established therapy, particularly in the field of neonatal and pediatric medicine. To reduce the priming volume of the extracorporeal circuit, different components can be combined. In this study, an oval-shaped oxygenator (called ExMeTrA) with integrated pulsatile pump was tested in vitro using porcine blood. A feasibility study regarding the performance of collapsing and expanding silicone tubes within an oxygenator fiber bundle as a pulsatile pump was previously completed with successful results. The findings of this study improve upon the previous feasibility results, particularly in terms of gas exchange and filling volume. Five modules were manufactured in sizes of 20 ± 2.2 ml (priming volume) with fiber surface areas of 0.24 ± 0.027 m2 and an analytically calculated volume pumping capacity of 692 ± 75 ml/min. The modules were made of polymethylpentene fibers with dense outer layer to permit long-term applications. The gas exchange rates at a gas/blood flow ratio of 2:1 were between 64 and 72.7 mlo2/lblood and between 62.5 and 81.5 ml/lblood, depending on the blood flow. The individual module’s pumping capacity ranged from 200–500 ml/min thus providing room for further improvements. In order to enhance the pumping capacity while maintaining sufficient gas exchange rates future optimization, adjustments will be made to the inlet and outlet geometries.

A validated CFD model to predict O2 and CO2 transfer within hollow fiber membrane oxygenators

Hollow fiber oxygenators provide gas exchange to and from the blood during heart surgery or lung recovery. Minimal fiber surface area and optimal gas exchange rate may be achieved by optimization of hollow fiber shape and orientation (1). In this study, a modified CFD model is developed and validated with a specially developed micro membrane oxygenator (MicroMox). The MicroMox was designed in such a way that fiber arrangement and bundle geometry are highly reproducible and potential flow channeling is avoided, which is important for the validation. Its small size (VFluid=0.04 mL) allows the simulation of the entire bundle of 120 fibers. A non-Newtonian blood model was used as simulation fluid. Physical solubility and chemical bond of O2 and CO2 in blood was represented by the numerical model. Constant oxygen partial pressure at the pores of the fibers and a steady state flow field was used to calculate the mass transport. In order to resolve the entire MicroMox fiber bundle, the mass transport was simulated for symmetric geometry sections in flow direction. In vitro validation was achieved by measurements of the gas transfer rates of the MicroMox. All measurements were performed according to DIN EN 12022 (2) using porcine blood. The numerical simulation of the mass transfer showed good agreement with the experimental data for different mass flows and constant inlet partial pressures. Good agreement could be achieved for two different fiber configurations. Thus, it was possible to establish a validated model for the prediction of gas exchange in hollow fiber oxygenators.

Consequences Arising From Elevated Surface Temperatures on Human Blood

Heat in blood pumps is generated by losses of the electrical motor and bearings. In the presented study the influence of tempered surfaces on bulk blood and adhesions on these surfaces was examined. Titanium alloy housing dummies were immersed in 25 mL heparinized human blood. The dummies were constantly tempered at specific temperatures (37-45 °C) over 15 min. Blood samples were withdrawn for blood parameter analysis and the determination of the plasmatic coagulation cascade. The quantities of adhesion on surfaces were determined by drained weight. Blood parameters do not alter significantly up to surface temperatures of 45 °C. In comparison to the control specimen, a drop in the platelet count can be observed, but is not significantly temperature dependent. The mean mass of adhesions at 41 °C increased up to 66% compared to 37 °C. Thus, heat generated in electrical motors and contact bearings may influence the amount of adhesions on surfaces.

Gas exchange efficiency of an oxygenator with integrated pulsatile displacement blood pump for neonatal patients

Oxygenators have been used in neonatal extracorporeal membrane oxygenation (ECMO) since the 1970s. The need to develop a more effective oxygenator for this patient cohort exists due to their size and blood volume limitations. This study sought to validate the next design iteration of a novel oxygenator for neonatal ECMO with an integrated pulsatile displacement pump, thereby superseding an additional blood pump. Pulsating blood flow within the oxygenator is generated by synchronized active air flow expansion and contraction of integrated silicone pump tubes and hose pinching valves located at the oxygenator inlet and outlet. The current redesign improved upon previous prototypes by optimizing silicone pump tube distribution within the oxygenator fiber bundle; introduction of an oval shaped inner fiber bundle core, and housing; and a higher fiber packing density, all of which in combination reduced the priming volume by about 50% (50 to 27 mL and 41 to 20 mL, respectively). Gas exchange efficiency was tested for two new oxygenators manufactured with different fiber materials: one with coating and one with smaller pore size, both capable of long-term use (OXYPLUS® and CELGARD®). Results demonstrated that the oxygen transfer for both oxygenators was 5.3-24.7 mlo2/min for blood flow ranges of 100-500 mlblood /min. Carbon dioxide transfer for both oxygenators was 3.7-26.3 mlCo2/min for the same blood flow range. These preliminary results validated the oxygenator redesign by demonstrating an increase in packing density and thus in gas transfer, an increase in pumping capacity and a reduction in priming volume.

Impact of Hyperthermal Rotary Blood Pump Surfaces on Blood Clotting Behavior: An Approach

The influence of heat dissipating systems, such as rotary blood pumps, was investigated. Titanium cylinders as rotary blood pump housing dummies were immersed in porcine blood and constantly tempered at specific temperatures (37-60 degrees C) over a defined period of time. The porcine blood was anticoagulated either by low heparin dosage or citrate. At frequent intervals, samples were taken for blood analysis and the determination of the plasmatic coagulation cascade. Blood parameters do not alter at surface temperatures below 50 degrees C. Hyperthermia-induced hemolysis could be confirmed. The plasmatic coagulation cascade is terminated at surface temperatures exceeding 55 degrees C. The adhesion of blood constituents on surfaces is temperature and time dependent, and structural changes of adhesions and blood itself were detected.

The Impact of Hyperthermal Surfaces on Blood in Vitro - An Approach

The influence of heat dissipating systems, such as blood pumps, was investigated. Titanium cylinders as blood pump housing dummies were immersed in porcine blood and constantly tempered at specific temperatures (37 °C - 60 °C) over a defined period of time. The porcine blood was anticoagulated either by low heparin dosage or citrate. At frequent intervals, samples were taken for blood analysis and the determination of the plasmatic coagulation cascade.

The Aachen MiniHLM - A Miniaturized Heart Lung Machine for Neonates with Congenital Heart Defect

Predominantly standard adult Heart Lung Ma chines (HLMs) are used for pediatric cardiac surgery, only with individually downsized components. Downsizing is limited, e.g. by the required gas exchange surface, etc. In order to diminish complications we developed a new miniaturized heart lung machine (Aachen MiniHLM) for neonates, with significantly reduced priming volume and blood contact surface by integration of all major system components in one single de vice. In particular, the MiniHLM is a Heart-Lung-Machine with the rotary blood pump centrically integrated into the oxygenator and the cardiotomy reservoir with integrated heat exchanger is directly connected. Thus, tubing is only necessary between patient and MiniHLM.