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Competing Interests: Disclosure: The authors have no conflicts of interest to report.

Pediatric heart failure (HF) patients have been a historically underserved population for mechanical circulatory support (MCS) therapy. To address this clinical need, we are developing a low cost, universal magnetically levitated extracorporeal system with interchangeable pump heads for pediatric support. Two impeller and pump designs (pump V1 and V2) for the pediatric pump were developed using dimensional analysis techniques and classic pump theory based on defined performance criteria (generated flow, pressure, and impeller diameter). The designs were virtually constructed using computer-aided design (CAD) software and 3D flow and pressure features were analyzed using computational fluid dynamics (CFD) analysis. Simulated pump designs (V1, V2) were operated at higher rotational speeds (~5,000 revolutions per minute [RPM]) than initially estimated (4,255 RPM) to achieve the desired operational point (3.5 L/min flow at 150 mm Hg). Pump V2 outperformed V1 by generating approximately 30% higher pressures at all simulated rotational speeds and at 5% lower priming volume. Simulated hydrodynamic performance (achieved flow and pressure, hydraulic efficiency) of our pediatric pump design, featuring reduced impeller size and priming volume, compares favorably to current commercially available MCS devices., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Administration of inhaled nitric oxide (NO) with the existing compressed gas delivery systems is associated with unavoidable codelivery of nitrogen dioxide (NO2), an unwanted toxic contaminant that forms when mixed with oxygen. The NO2 is generated when NO is diluted with O2-enriched air before delivery to the patient. When NO2 is inhaled by the patient, it oxidizes protective antioxidants within the epithelial lining fluid (ELF) and triggers extracellular damage in the airways. The reaction of NO2 within the ELF triggers oxidative stress (OS), possibly leading to edema, bronchoconstriction, and a reduced forced expiratory volume in 1 second. Nitrogen dioxide has been shown to have deleterious effects on the airways of high-risk patients including neonates, patients with respiratory and heart failure, and the elderly. Minimizing co-delivery of NO2 for the next generation delivery systems will be a necessity to fully optimize the pulmonary perfusion of NO because of vasodilation, whereas minimizing the negative ventilatory and histopathological effects of NO2 exposure during inhaled NO therapy.

The Levitronix PediVAS is an extracorporeal magnetically levitated pediatric ventricular assist system with an optimal flow rate range of 0.3-1.5 L/min. The system is being tested in preclinical studies to assess hemodynamic performance and biocompatibility. The PediVAS was implanted in nine ovines for 30 days using either commercially available cannulae (n = 3) or customized Levitronix cannulae (n = 6). Blood biocompatibility in terms of circulating activated platelets was measured by flow cytometric assays to detect P-selectin. Platelet activation was further examined after exogenous agonist stimulation. Platelet activation increased after surgery and eventually returned to baseline in animal studies where minimal kidney infarcts were observed. Platelet activation remained elevated for the duration of the study in animals where a moderate number of kidney infarcts with or without thrombotic deposition in the cannulae were observed. When platelet activation did return to baseline, platelets appropriately responded to agonist stimulation, signifying conserved platelet function after PediVAS implant. Platelet activation returned to baseline in the majority of studies, representing a promising biocompatibility result for the Levitronix PediVAS.

This study tested the impact of different postpump resistances on pulsatile pressure-flow waveforms and hemodynamic energy output in a mock extracorporeal system. The circuit was primed with a 40% glycerin-water mixture, and a PediVAS centrifugal pump was used. The pre- and postpump pressures and flow rates were monitored via a data acquisition system. The postpump resistance was adjusted using a Hoffman clamp at the outlet of the pump. Five different postpump resistances and rotational speeds were tested with nonpulsatile (NP: 5000 RPM) and pulsatile (P: 4000 RPM) modes. No backflow was found when using pulsatile flow. With isoresistance, increased arterial resistances decreased pump flow rates (NP: from 1,912 ml/min to 373 ml/min; P: from 1,485 ml/min to 288 ml/min), increased postpump pressures (NP: from 333 mm Hg to 402 mm Hg; P: from 223 mm Hg to 274 mm Hg), and increased hemodynamic energy output with pulsatile mode. Pump flow rate correlated linearly with rotational speed (RPMs) of the pump, whereas postpump pressures and hemodynamic energy outputs showed curvilinear relationships with RPMs. The maximal pump flow rate also increased from 618 ml/min to 4,293 ml/min with pulsatile mode and from 581 ml/min to 5,665 ml/min with nonpulsatile mode. Results showed that higher postpump resistance reduced the pump flow range, and increased postpump pressure and surplus hemodynamic energy output with pulsatile mode. Higher rotational speeds also generated higher pump flow rates, postpump pressures, and increased pulsatility.

The objective of this study was to test different pulsatile flow settings of the PediVAS centrifugal pump to seek an optimum setting for pulsatile flow to achieve better pulsatile energy and minimal backflow. The PediVAS centrifugal pump and the conventional pediatric clinical circuit, including a pediatric membrane oxygenator, arterial filter, arterial cannula, and 1/4 in circuit tubing were used. The circuit was primed with 40% glycerin water mixture. Postcannula pressure was maintained at 40 mm Hg by a Hoffman clamp. The experiment was conducted at 800 ml/min of pump flow with a modified pulsatile flow setting at room temperature. Pump flow and pressure readings at preoxygenator and precannula sites were simultaneously recorded by a data acquisition system. The results showed that backflows appeared at flow rates of 200-800 ml/min (200 ml/min increments) with the default pulsatile flow setting and only at 200 ml/min with the modified pulsatile flow setting. With an increased rotational speed difference ratio and a decreased pulsatile width, the pulsatility increased in terms of surplus hemodynamic energy and total hemodynamic energy at preoxygenator and precannula sites. Backflows seemed at preoxygenator and precannula sites at a 70% of rotational speed difference ratio. The modified pulsatile flow setting was better than the default pulsatile flow setting in respect to pulsatile energy and backflow. The pulsatile width and the rotational speed difference ratio significantly affected pulsatility. The parameter of the rotational speed difference ratio can automatically increase pulsatility with increased rotational speeds. Further studies will be conducted to optimize the pulsatile flow setting of the centrifugal pump.

The hemodynamic comparison of the Jostra HL-20 and the Levitronix PediVAS blood pumps is the focus this study, where pressure-flow waveforms and hemodynamic energy values are analyzed in the confines of a pediatric cardiopulmonary bypass circuit.The pseudo pediatric patient was perfused with flow rates between 500 and 900 ml/min (100 ml/min increments) under pulsatile and nonpulsatile mode. The Levitronix continuous flow pump utilized a customized controller to engage in pulsatile perfusion with equivalent pulse settings to the Jostra HL-20 roller pump. Hemodynamic measurements and waveforms were recorded at the precannula location, while the mean arterial pressure was maintained at 40 mm Hg for each test. Glycerin water was used as the blood analog circuit perfusate. At each flow rate 24 trials were conducted yielding a total of 120 experiments (n=60 pulsatile and n=60 nonpulsatile).Under nonpulsatile perfusion the Jostra roller pump produced small values for surplus hemodynamic energy (SHE) due to its inherent pulsatility, while the Levitronix produced values of essentially zero for SHE. When switching to pulsatile perfusion, the SHE levels for both the Jostra and Levitronix pump made considerable increases. In comparing the two pumps under pulsatile perfusion, the Levitronix PediVAS produced significantly more surplus and total hemodynamic energy than did the Jostra roller pump each pump flow rate.The study suggests that the Levitronix PediVAS centrifugal pump has the capability of achieving quality pulsatile waveforms and delivering more SHE to the pseudo patient than the Jostra HL-20 roller pump. Further studies are warranted to investigate the Levitronix under bovine blood studies and with various pulsatile settings.

The treatment of children with life-threatening cardiac and cardiopulmonary failure is a large and underappreciated public health concern. We have previously shown that the CentriMag is a magnetically levitated centrifugal pump system, having the utility for treating adults and large children (1,500 utilized worldwide). We present here the PediVAS, a pump system whose design was modified from the CentriMag to meet the physiological requirements of young pediatric and neonatal patients. The PediVAS is comprised of a single-use centrifugal blood pump, reusable motor, and console, and is suitable for right ventricular assist device (RVAD), left ventricular assist device (LVAD), biventricular assist device (BVAD), or extracorporeal membrane oxygenator (ECMO) applications. It is designed to operate without bearings, seals and valves, and without regions of blood stasis, friction, or wear. The PediVAS pump is compatible with the CentriMag hardware, although the priming volume was reduced from 31 to 14 ml, and the port size reduced from 3/8 to (1/4) in. For the expected range of pediatric flow (0.3-3.0 L/min), the PediVAS exhibited superior hydraulic efficiency compared with the CentriMag. The PediVAS was evaluated in 14 pediatric animals for up to 30 days, demonstrating acceptable hydraulic function and hemocompatibility. The current results substantiate the performance and biocompatibility of the PediVAS cardiac assist system and are likely to support initiation of a US clinical trial in the future.

The development of microfluidic devices supporting physiological blood flow has the potential to yield biomedical technologies emulating human organ function. However, advances in this area have been constrained by the fact that artificial microchannels constructed for such devices need to achieve maximum chemical diffusion as well as hemocompatibility. To address this issue, we designed an elastomeric microfluidic flow device composed of poly (dimethylsiloxane) to emulate the geometry and flow properties of the pulmonary microcirculation. Our chip design is characterized by high aspect ratio (width > height) channels in an orthogonally interconnected configuration. Finite element simulations of blood flow through the network design chip demonstrated that the apparent pressure drop varied in a linear manner with flow rate. For simulated flow rates <250 mul min, the simulated pressure drop was <2000 Pa, the flow was laminar, and hemolysis was minimal. Hemolysis rate, assayed in terms of [total plasma hemoglobin (TPH) (sample - control)/(TPH control)] during 6 and 12 hour perfusions at 250 mul/min, was <5.0% through the entire period of device perfusion. There was no evidence of microscopic thrombus at any channel segment or junction under these perfusion conditions. We conclude that a microfluidic blood flow device possessing asymmetric and interconnected microchannels exhibits uniform flow properties and preliminary hemocompatibility. Such technology should foster the development of miniature oxygenators and similar biomedical devices requiring both a microscale reaction volume and physiological blood flow.

We evaluated the effects of the Levitronix UltraMag pediatric ventricular assist system on healthy animals during 29- to 90-day periods by assessing hemocompatibility and hepatic and renal functions while operating the device in a flow range suitable for pediatric patients. Nine lambs (weight, 15 to 24 kg) received the Levitronix UltraMag with an outflow cannula anastomosed to the descending aorta and an inflow cannula inserted into the left ventricular apex. Pump function data were collected at 1-hour intervals, and postoperative hematology and clinical chemistry tests were performed weekly throughout the study. Complete necropsy and histopathologic examinations were performed at study termination. Pump and circuit were thoroughly inspected for evidence of thrombi. All animals reached the scheduled endpoint of 29 to 90 days without device-related problems. Mean flow was maintained at 1.14 +/- 0.19 L/min. Hematologic values were within normal range in all animals except in one lamb that had a severe hemolytic reaction after cefazolin sodium administration. In all animals, serum glutamic-oxaloacetic transaminase and creatinine kinase levels increased after surgery but gradually returned to normal limits within 1 week. Postmortem examination of the explanted organs revealed small infarcted areas in five lamb kidneys, but renal function was unaffected. All other major organs were unremarkable. In one explanted pump (a 30-day study), a small thrombus was seen within the impeller blade. The other eight pumps were free of thrombus. The Levitronix UltraMag successfully operated in pediatric flow ranges without device-related adverse events.

A miniature Maglev blood pump based on magnetically levitated bearingless technology is being developed and optimized for pediatric patients. We performed impeller optimization by characterizing the hemodynamic and hemocompatibility performances using a combined computational and experimental approach. Both three-dimensional flow features and hemolytic characteristics were analyzed using computational fluid dynamics (CFD) modeling. Hydraulic pump performances and hemolysis levels of three different impeller designs were quantified and compared numerically. Two pump prototypes were constructed from the two impeller designs and experimentally tested. Comparison of CFD predictions with experimental results showed good agreement. The optimized impeller remarkably increased overall pump hydraulic output by more than 50% over the initial design. The CFD simulation demonstrated a clean and streamlined flow field in the main flow path. The numerical results by hemolysis model indicated no significant high shear stress regions. Through the use of CFD analysis and bench-top testing, the small pediatric pump was optimized to achieve a low level of blood damage and improved hydraulic performance and efficiency. The Maglev pediatric blood pump is innovative due to its small size, very low priming volume, excellent hemodynamic and hematologic performance, and elimination of seal-related and bearing-related failures due to adoption of magnetically levitated bearingless motor technology, making it ideal for pediatric applications.

The severely debilitating nature of chronic lung disease has long provided the impetus for the development of technologies to supplement the respiratory capacity of the human lung. Although conventional artificial lung technologies function by delivering pressurized oxygen to the blood through a system of hollow fibers or tubes, our approach uses photolytic energy to generate dissolved oxygen (DO) from the water already present in blood, thus eliminating the need for gas delivery. We have previously demonstrated that it is feasible to generate dissolved oxygen from water based on UVA illumination of a highly absorbent TiO2 thin film. In the current study, we extend this work by using photolytic energy to generate DO from whole blood, thus resulting in an increase of oxyhemoglobin as a function of back side TiO2 surface film illumination. Initial experiments, performed with Locke's Ringer solution, demonstrated effective film thickness and material selection for the conductive layer. The application of a small bias voltage was used to conduct photogenerated electrons from the aqueous phase to minimize electron recombination with the DO.Mixed arterial-venous bovine blood was flowed in a recirculating loop over TiO2 nanocrystalline films illuminated on the side opposite the blood (or "back side") to eliminate the possibility of any direct exposure of blood to light. After light exposure of the TiO2 film, the fraction of oxyhemoglobin in the blood rapidly increased to near saturation and remained stable throughout the trial period. Last, we evaluated potential biofouling of the DO generating surface by scanning electron microscopy, after photolytically energized DO generation in whole blood, and observed no white or red blood cell surface deposition, nor the accumulation of any other material at this magnification. We conclude that it is feasible to photolytically oxygenate the hemoglobin contained in whole blood with oxygen derived from the blood's own water content without involving a gaseous phase.

There is an established need for pulmonary technology capable of facilitated gas exchange in the blood, thereby bypassing the alveolar-capillary interface. To address this need, we emulated one of the best-known photolytic reactions in nature, photosynthesis, in which green plants use sunlight to drive the exchange of oxygen for carbon dioxide. Our goal in the current study was to demonstrate the feasibility of direct photolytic conversion of water to liquid phase oxygen (dissolved oxygen [DO]) in synthetic serum. To this end, we constructed a test flow cell consisting of a conductive coating of vacuum-deposited titanium (Ti) metal, adherent TiO2 (anatase), and MnO2, applied as a laminate to a glass substrate, and then immersed the device in Locke's-Ringer solution (synthetic blood serum). Long wavelength (low energy) ultraviolet A laser light, directed to the transparent glass slide, reproducibly resulted in the generation of an active form of oxygen (AO), which was subsequently converted directly by the catalytic action of MnO2 to DO. The absence of light activation provided an entirely null response. We conclude that the photolytic production of DO from water in a blood serum surrogate, with commensurate CO2 clearance, is feasible. A prototype photolytic module is proposed, which uses multiple parallel photolytic surfaces to improve system production capacity and CO2 clearance through selective gas-liquid separation from the oxygen-enriched fluid.