Pulsatile venous waveform quality affects the conduit performance in functional and "failing" Fontan circulations.

OBJECTIVE: To investigate the effect of pulsatility of venous flow waveform in the inferior and superior caval vessels on the performance of functional and "failing" Fontan patients based on two primary performance measures - the conduit power loss and the distribution of inferior caval flow (hepatic factors) to the lungs. METHODS: Doppler angiography flows were acquired from two typical extra-cardiac conduit "failing" Fontan patients, aged 13 and 25 years, with ventricle dysfunction. Using computational fluid dynamics, haemodynamic efficiencies of "failing", functional, and in vitro-generated mechanically assisted venous flow waveforms were evaluated inside an idealised total cavopulmonary connection with a caval offset. To investigate the effect of venous pulsatility alone, cardiac output was normalised to 3 litres per minute in all cases. To quantify the pulsatile behaviour of venous flows, two new performance indices were suggested. RESULTS: Variations in the pulsatile content of venous waveforms altered the conduit efficiency notably. High-frequency and low-amplitude oscillations lowered the pulsatile component of the power losses in "failing" Fontan flow waveforms. Owing to the offset geometry, hepatic flow distribution depended strongly on the ratio of time-dependent caval flows and the pulsatility content rather than mixing at the junction. "Failing" Fontan flow waveforms exhibited less balanced hepatic flow distribution to lungs. CONCLUSIONS: The haemodynamic efficiency of single-ventricle circulation depends strongly on the pulsatility of venous flow waveforms. The proposed performance indices can be calculated easily in the clinical setting in efforts to better quantify the energy efficiency of Fontan venous waveforms in pulsatile settings.

Platelet activation in ovines undergoing sham surgery or implant of the second generation PediaFlow pediatric ventricular assist device.

The PediaFlow pediatric ventricular assist device (VAD) is a magnetically levitated turbodynamic pump under development for circulatory support of small children with a targeted flow rate range of 0.3-1.5 L/min. As the design of this device is refined, ensuring high levels of blood biocompatibility is essential. In this study, we characterized platelet activation during the implantation and operation of a second generation prototype of the PediaFlow VAD (PF2) and also performed a series of surgical sham studies to examine purely surgical effects on platelet activation. In addition, a newly available monoclonal antibody was characterized and shown to be capable of quantifying ovine platelet activation. The PF2 was implanted in three chronic ovine experiments of 17, 30, and 70 days, while surgical sham procedures were performed in five ovines with 30-day monitoring. Blood biocompatibility in terms of circulating activated platelets was measured by flow cytometric assays with and without exogenous agonist stimulation. Platelet activation following sham surgery returned to baseline in approximately 2 weeks. Platelets in PF2-implanted ovines returned to baseline activation levels in all three animals and showed an ability to respond to agonist stimulation. Late-term platelet activation was observed in one animal corresponding with unexpected pump stoppages related to a manufacturing defect in the percutaneous cable. The results demonstrated encouraging platelet biocompatibility for the PF2 in that basal platelet activation was achieved early in the pump implant period. Furthermore, this first characterization of the effect of a major cardiothoracic procedure on temporal ovine platelet activation provides comparative data for future cardiovascular device evaluation in the ovine model.

Month-long Respiratory Support by a Wearable Pumping Artificial Lung in an Ovine Model.

BACKGROUND: A wearable artificial lung could improve lung transplantation outcomes by easing implementation of physical rehabilitation during long-term pretransplant respiratory support. The Modular Extracorporeal Lung Assist System (ModELAS) is a compact pumping artificial lung currently under development. This study evaluated the long-term in vivo performance of the ModELAS during venovenous support in awake sheep. Feedback from early trials and computational fluid dynamic analysis guided device design optimization along the way. METHODS: The ModELAS was connected to healthy sheep via a dual-lumen cannula in the jugular vein. Sheep were housed in a fixed-tether pen while wearing the device in a holster during support. Targeted blood flow rate and support duration were 2-2.5 L/min and 28-30 days, respectively. Anticoagulation was maintained via systemic heparin. Device pumping and gas exchange performance and hematologic indicators of sheep physiology were measured throughout support. RESULTS: Computational fluid dynamic-guided design modifications successfully decreased pump thrombogenicity from initial designs. For the optimized design, 4 of 5 trials advancing past early perioperative and cannula-related complications lasted the full month of support. Blood flow rate and CO2 removal in these trials were 2.1 ± 0.3 L/min and 139 ± 15 mL/min, respectively, and were stable during support. One trial ended after 22 days of support due to intradevice thrombosis. Support was well tolerated by the sheep with no signs of hemolysis or device-related organ impairment. CONCLUSIONS: These results demonstrate the ability of the ModELAS to provide safe month-long support without consistent deterioration of pumping or gas exchange capabilities.

In vivo testing of the low-flow CO2 removal application of a compact, platform respiratory device.

BACKGROUND: Non-invasive and lung-protective ventilation techniques may improve outcomes for patients with an acute exacerbation of chronic obstructive pulmonary disease or moderate acute respiratory distress syndrome by reducing airway pressures. These less invasive techniques can fail due to hypercapnia and require transitioning patients to invasive mechanical ventilation. Extracorporeal CO2 removal devices remove CO2 independent of the lungs thereby controlling the hypercapnia and permitting non-invasive or lung-protective ventilation techniques. We are developing the Modular Extracorporeal Lung Assist System as a platform technology capable of providing three levels of respiratory assist: adult and pediatric full respiratory support and adult low-flow CO2 removal. The objective of this study was to evaluate the in vivo performance of our device to achieve low-flow CO2 removal. METHODS: The Modular Extracorporeal Lung Assist System was connected to 6 healthy sheep via a 15.5 Fr dual-lumen catheter placed in the external jugular vein. The animals were recovered and tethered within a pen while supported by the device for 7 days. The pump speed was set to achieve a targeted blood flow of 500 mL/min. The extracorporeal CO2 removal rate was measured daily at a sweep gas independent regime. Hematological parameters were measured pre-operatively and regularly throughout the study. Histopathological samples of the end organs were taken at the end of each study. RESULTS: All animals survived the surgery and generally tolerated the device well. One animal required early termination due to a pulmonary embolism. Intra-device thrombus formation occurred in a single animal due to improper anticoagulation. The average CO2 removal rate (normalized to an inlet pCO2 of 45 mmHg) was 75.6 ± 4.7 mL/min and did not significantly change over the course of the study (p > 0.05). No signs of consistent hemolysis or end organ damage were observed. CONCLUSION: These in vivo results indicate positive performance of the Modular Extracorporeal Lung Assist System as a low-flow CO2 removal device.

Cell therapy for ARDS: efficacy of endobronchial versus intravenous administration and biodistribution of MAPCs in a large animal model.

Introduction: Bone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement on which is the best method for stem cells delivery in ARDS. Here, we compared the efficacy of two different methods of administration and biodistribution of MAPC for the treatment of ARDS in a sheep model. Methods: MAPC were labelled with [18F] fluoro-29-deoxy-D-glucose and delivered by endobronchial (EB) or intravenous route 1 hour after lipopolysaccharide infusion in sheep mechanically ventilated. PET/CT images were acquired to determine the biodistribution and retention of the cells at 1 and 5 hours of administration. Results: The distribution and retention of the MAPC was dependent on the method of cell administration. By EB route, PET images showed that MAPC remained at the site of administration and no changes were observed after 5 hours, whereas with intravenous route, the cells had broad biodistribution to different organs, being the lung the main organ of retention at 1 and 5 hours. MAPC demonstrated an equal effect on arterial oxygenation recovery by either route of administration. Conclusion: The EB or intravenous routes of administration of MAPC are both effective for the treatment of ARDS in an acute sheep model, and the effect of MAPC therapy is not dependent of parenchymal integration or systemic biodistribution.

Preclinical performance of a pediatric mechanical circulatory support device: The PediaFlow ventricular assist device.

OBJECTIVES: The PediaFlow (HeartWare International, Inc, Framingham, Mass) is a miniature, implantable, rotodynamic, fully magnetically levitated, continuous-flow pediatric ventricular assist device. The fourth-generation PediaFlow was evaluated in vitro and in vivo to characterize performance and biocompatibility. METHODS: Supported by 2 National Heart, Lung, and Blood Institute contract initiatives to address the limited options available for pediatric patients with congenital or acquired cardiac disease, the PediaFlow was developed with the intent to provide chronic cardiac support for infants as small as 3 kg. The University of Pittsburgh-led Consortium evaluated fourth-generation PediaFlow prototypes both in vitro and within a preclinical ovine model (n = 11). The latter experiments led to multiple redesigns of the inflow cannula and outflow graft, resulting in the implantable design represented in the most recent implants (n = 2). RESULTS: With more than a decade of extensive computational and experimental efforts spanning 4 device iterations, the AA battery-sized fourth-generation PediaFlow has an operating range of 0.5 to 1.5 L/min with minimal hemolysis in vitro and excellent hemocompatibility (eg, minimal hemolysis and platelet activation) in vivo. The pump and finalized accompanying implantable components demonstrated preclinical hemodynamics suitable for the intended pediatric application for up to 60 days. CONCLUSIONS: Designated a Humanitarian Use Device for "mechanical circulatory support in neonates, infants, and toddlers weighing up to 20 kg as a bridge to transplant, a bridge to other therapeutic intervention such as surgery, or as a bridge to recovery" by the Food and Drug Administration, these initial results document the biocompatibility and potential of the fourth-generation PediaFlow design to provide chronic pediatric cardiac support.

The Use of GMP-Produced Bone Marrow-Derived Stem Cells in Combination with Extracorporeal Membrane Oxygenation in ARDS: An Animal Model.

Acute respiratory distress syndrome (ARDS) is the result of a wide variety of disorders, which can be associated with different clinical disorders or systemic diseases directly affecting the lungs. Currently, the only existing therapy is limited to supportive care. In a 6 hour pilot study, we analyzed the use of the combination of both stem cell and extracorporeal membrane oxygenation (ECMO) strategies to prevent or treat severe lung injury. A total of 11 sheep were used. Five sheep received Escherichia coli endotoxin as a control group (group 1). Three sheep that received E. coli endotoxin were treated with veno-venous ECMO support in group 2. In group 3, 3 sheep received a dose of clinical grade good manufacturing practice (GMP)-produced MultiPotent Adult Progenitor cells (MAPC) intratracheally after the end of the infusion of E. coli endotoxin, followed by ECMO support. The respiratory parameters by means of blood gas results, measurements of lung injury, inflammatory responses, and integrity of the alveolar capillary barrier after the infusion of these cells were analyzed. Our data suggest that the combination of ECMO and stem cell therapy showed better histopathologic changes with less inflammation. We believe that the combination of stem cells with the ECMO treatment may be useful in future studies investigating the diagnosis, treatment, and prevention of ARDS.

Extending the boundaries of the primary arterial switch operation in patients with transposition of the great arteries and intact ventricular septum.

BACKGROUND: We have previously suggested that the primary arterial switch operation is a feasible strategy for patients with transposition of the great arteries and intact ventricular septum (TGA-IVS) up to age 2 months. This study reports our current results with this approach and examines whether this policy could be extended beyond age 2 months. METHODS AND RESULTS: 380 patients who underwent arterial switch for TGA-IVS were reviewed. 275 patients were younger than 3 weeks at the time of surgery (early switch group); 105 patients were 3 weeks or older (range, 21 to 185 days) (late switch group). There was no difference in outcome in terms of in-hospital mortality (5.5% versus 3.8%) or need for mechanical circulatory support (3.6% versus 5.7%) between early and late switch groups. However, duration of postoperative ventilation (4.9 versus 7.1 days, P=0.012) and length of postoperative stay (12.5 versus 18.9 days, P<0.001) were significantly prolonged in the late switch group. Primary left ventricular failure resulting in death occurred in 2 patients in the late switch group, with no deaths in 9 patients aged 2 to 6 months. CONCLUSIONS: This experience confirms that in TGA-IVS, the left ventricle maintains the potential for systemic work well beyond the first month of life. Consequently, neonates at high risk or late referrals can benefit from delayed arterial switch, even beyond age 2 months. However, the need for mechanical support in some of the older patients may limit the widespread adoption of such a strategy.

On the use of computational models for the quantitative assessment of surgery in congenital heart disease.

The surgical repair of congenital heart disease often involves significant modifications to the circulatory tree. Resections, reconstructions, graft insertions and the deployment of implants and biomedical devices have an impact on local and systemic haemodynamics, which may be difficult to foresee or to assess quantitatively by clinical investigation alone. Mathematical models can be employed to visualise, estimate or predict events and physical quantities that are difficult to observe or measure, and can be successfully applied to the study of the pre- and post-operative physiology of cardiovascular malformations. This paper analyses the potentialities of computation fluid dynamics in this respect, outlining the method, its requirements and its limitations. Examples are given of lumped parameter models, axi-symmetric models, three-dimensional models, fluid-structure interaction simulations and multiscale computing applied to total cavo-pulmonary connection, aortic coarctation and aortic arch reconstruction.

Long-segment tracheal stenosis: slide tracheoplasty and a multidisciplinary approach improve outcomes and reduce costs.

OBJECTIVE: Long-segment tracheal stenosis is rare, life-threatening, difficult, and expensive to treat. Management remains controversial. A multidisciplinary tracheal team was formed in 2000 to deal with a large number of children with airway problems referred for management. We review the effect of that service, comparing the era before and after the establishment of the multidisciplinary tracheal team. METHODS: From January 1998 through January 2004, 34 patients with long-segment tracheal stenosis (21 patients with cardiovascular anomalies) underwent surgical intervention. Cardiopulmonary bypass was used in all operations. Before the multidisciplinary tracheal team, pericardial patch tracheoplasty with or without an autograft technique was the preferred method of repair. After the multidisciplinary tracheal team, an integrated care plan preferring slide tracheoplasty was initiated, correcting cardiac lesions simultaneously. RESULTS: Before the establishment of the multidisciplinary tracheal team, pericardial patch tracheoplasty was performed in 15 of 19 patients. Twelve patients had a suspended pericardial patch tracheoplasty, 2 (17%) of whom died late after the operation. Of 3 patients who had had a simple unsuspended patch, 2 (67%) died early after the operation. Four patients were operated on with the tracheal autograft technique, 2 (50%) dying early in the postoperative period. After multidisciplinary tracheal team formation, in the era between 2001 and 2004, 15 patients were operated on with slide tracheoplasty, and there were 2 (13%) early postoperative deaths. A significant reduction in cost and duration of stay has been shown both in the intensive care unit and the hospital. CONCLUSION: Our data suggest that a formalized multidisciplinary team approach and a policy of primary slide tracheoplasty are beneficial in the management of children with long-segment tracheal stenosis.

[The presence of Chlamydophila pneumoniae, Helicobacter pylori and cytomegalovirus in human atherosclerosis detected by molecular and serological methods]. / Aterosklerozda Chlamydophila pneumoniae, Helicobacter pylori ve cytomegalovirus varliginin moleküler ve serolojik yöntemlerle arastirilmasi.

Persistant infections due to Chlamydophila pneumoniae, Helicobacter pylori, and Cytomegalovirus are suggested to contribute to the development of atherosclerosis. In this study, the presence of these agents was investigated by polymerase chain reaction (PCR) and serological tests in atherosclerotic plaques and non-atherosclerotic vessel samples. Thirty-three specimens from the atherosclerotic plaques (lesion group), 45 specimens from the healthy left internal mammarian arteries and ascending aortas of the atherosclerotic patients (non-lesion group), and 15 specimens from the aortas of non-atherosclerotic patients as determined by angiography (control group), were included to the study. Serum samples were also collected from all study subjects for the serological investigation. PCR and ELISA were used in order to determine the nucleic acid positivity and IgG titers, respectively. C. pneumoniae and H. pylori DNA were found in 6 (18.1%) and 14 (42.4%) of the lesion group, 2 (4.4%) and 9 (20%) of the non-lesion group, respectively. CMV DNA was not found in either groups. All of the PCR results of control group were negative. C. pneumoniae IgG was found positive in one case of the lesion group (3%) and three cases of the non-lesion group (6.7%). H. pylori IgG were positive in all the subjects except for three patients who were in the non-lesion group. The presence of C. pneumoniae and H. pylori DNA in a considerable number of lesion and non-lesion groups' specimens, but absence in control group specimens supports the hypothesis that these agents have an association with atherosclerosis.

Pre-clinical evaluation of an adult extracorporeal carbon dioxide removal system with active mixing for pediatric respiratory support.

The objective of this work was to conduct pre-clinical feasibility studies to determine if a highly efficient, active-mixing, adult extracorporeal carbon dioxide removal (ECCO2R) system can safely be translated to the pediatric population. The Hemolung Respiratory Assist System (RAS) was tested in vitro and in vivo to evaluate its performance for pediatric veno-venous applications. The Hemolung RAS operates at blood flows of 350-550 ml/min and utilizes an integrated pump-gas exchange cartridge with a membrane surface area of 0.59 m² as the only component of the extracorporeal circuit. Both acute and seven-day chronic in vivo tests were conducted in healthy juvenile sheep using a veno-venous cannulation strategy adapted to the in vivo model. The Hemolung RAS was found to have gas exchange and pumping capabilities relevant to patients weighing 3-25 kg. Seven-day animal studies in juvenile sheep demonstrated that veno-venous extracorporeal support could be used safely and effectively with no significant adverse reactions related to device operation.

Human adult bone marrow-derived stem cells decrease severity of lipopolysaccharide-induced acute respiratory distress syndrome in sheep.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is the most common cause of respiratory failure among critically ill subjects, sepsis and severe bacterial pneumonia being its most common causes. The only interventions that have proven beneficial are protective ventilation strategies and fluid conservation approaches. New therapies are needed to address this common clinical problem. Others and we have previously shown the beneficial effect of infusion of exogenous adult stem cells in different pre-clinical models of ARDS. METHODS: In the present study endotoxin was infused intravenously into 14 sheep from which 6 received different doses of adult stem cells by intrabronchial delivery to evaluate the effect of stem cell therapy. RESULTS: After administration of endotoxin, there was a rapid decline in oxygenation to hypoxemic values, indicative of severe-to-moderate ARDS. None of the animals treated with saline solution recovered to normal baseline values during the 6 hours that the animals were followed. In contrast, sheep treated with a dose of 40 million adult stem cells returned their levels of oxygen in their blood to baseline two hours after the cells were infused. Similarly, improvements in carbon dioxide (CO2) clearance, pulmonary vascular pressures and inflammation were observed and confirmed by histology and by the decrease in lung edema. CONCLUSIONS: We concluded that instillation of adult non-hematopoietic stem cells can diminish the impact of endotoxin and accelerate recovery of oxygenation, CO2 removal and inflammation in the ovine model, making the use of adult stem cells a real alternative for future therapies for ARDS.

Biocompatibility Assessment of the CentriMag-Novalung Adult ECMO Circuit in a Model of Acute Pulmonary Hypertension.

Extracorporeal membrane oxygenation (ECMO) is rarely used in patients with severe pulmonary hypertension (PH) as a bridge to lung transplantation. In this study, we assess the blood biocompatibility of the integrated CentriMag-Novalung ECMO system (venoarterial) in an acute model of PH. Severe PH (≥2/3 systemic) was induced in eight sheep through progressive ligation of the main pulmonary artery. System performance, platelet activation, thromboelastography (TEG) parameters, fibrinogen, plasma-free hemoglobin, and total plasma protein were measured at initiation, 3, and 6 hr of support in the ECMO (N = 4) and sham (N = 4) groups. A stable ECMO flow (2.2 ± 0.1 L/min), low transmembrane pressure gradient, and steady blood O2 and CO2 levels were maintained. Platelet activation was low (<4%) in both the groups, whereas platelet responsiveness to agonist (platelet activating factor) was reduced in the sham group when compared with the ECMO group. There were no differences in the TEG parameters, fibrinogen concentration, plasma-free hemoglobin (<10 mg/dl), and plasma total protein between the two groups. The findings of low levels of platelet activation and plfHb suggest adequate blood biocompatibility of the integrated CentriMag-Novalung circuit use for short-term support in a model of PH.

Pulsatile venous waveform quality in Fontan circulation-clinical implications, venous assists options and the future.

OBJECTIVE: Functionally univentricular heart (FUH) anomalies are the leading cause of death from all structural birth defects. Total cavopulmonary connection (TCPC) is the last stage of the palliative surgical reconstruction with significant late hemodynamic complications requiring high-risk heart transplantation. Alternative therapeutic options for these critically ill patients are crucial. In Phase I, we investigated the effect of pulsatility of venous flow (VF) waveform on the performance of functional and "failing" Fontan (FF) patients based on conduit power loss. In phase 2, the effect of enhanced external counter pulsation on Fontan circulation flow rates is monitored. METHODS: In phase 1, Doppler VFs were acquired from FF patients with ventricle dysfunction. Using computational fluid dynamics (CFD), hemodynamic efficiencies of the FF, functional and in-vitro generated mechanically assisted VF waveforms were evaluated. In phase 2, Fontan circulation on sheep model was created and enhanced external counter pulsation (EECP) applied. RESULTS: Variations in the pulsatile content of the VF waveforms altered conduit efficiency notably. High frequency and low amplitude oscillations lowered the pulsatile component of power losses in FF VF waveforms. The systemic venous flow, pulmonary artery and aorta flows increased by utilizing EECP. CONCLUSION: Our data highlighted the significance of VF pulsatility on energy efficiency inside SV circulation and the feasibility of VF waveform optimization. EECP assist in Fontan circulation can result in venous flow augmentation.

Platelet activation after implantation of the Levitronix PediVAS in the ovine model.

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.

Pre-clinical Implants of the Levitronix PediVAS® Pediatric Ventricular Assist Device - Strategy for Regulatory Approval.

The PediVAS blood pump is a magnetically levitated centrifugal pump designed for pediatric bridge-to-decision or bridge-to-recovery in pediatric patients from 3-20kg in weight. In preparation for submission of an investigational device exemption (IDE) application, we completed a final six-animal series of pre-clinical studies. The studies were conducted under controlled conditions as prescribed by the recently released FDA guidance document for animal studies for cardiovascular devices. Three 30-day chronic left ventricular support studies were completed in a juvenile lamb model to demonstrate the safety and hemocompatibility of the PediVAS pump. Three additional 8-hour acute biventricular support studies were performed to demonstrate the feasibility of this approach from a hemodynamic and systems standpoint. It is estimated that 50% of pediatric patients who require left ventricular support also require right ventricular support. All studies were successfully completed without complications, device malfunctions, or adverse events. End-organ function was normal for the chronic studies. We noted small surface lesions on one kidney from each chronic study as well as the presence of ring thrombus on connectors, as expected for these types of studies in animal models. The strategy and challenges imposed by performing a controlled cardiovascular device study in a juvenile lamb model are discussed. We believe that these successful implants demonstrate safety and performance for the PediVAS device for support of an IDE application to initiate human clinical trials and provide a roadmap for other researchers.

In Vitro and In Vivo Performance Evaluation of the Second Developmental Version of the PediaFlow Pediatric Ventricular Assist Device.

Ventricular assist devices (VADs) have significantly impacted the treatment of adult cardiac failure, but few options exist for pediatric patients. This has motivated our group to develop an implantable magnetically levitated rotodynamic VAD (PediaFlow®) for 3-20 kg patients. The second prototype design of the PediaFlow (PF2) is 56% smaller than earlier prototypes, and achieves 0.5-1.5 L/min blood flow rates. In vitro hemodynamic performance and hemolysis testing were performed with analog blood and whole ovine blood, respectively. In vivo evaluation was performed in an ovine model to evaluate hemocompatibility and end-organ function. The in vitro normalized index of hemolysis was 0.05-0.14 g/L over the specified operating range. In vivo performance was satisfactory for two of the three implanted animals. A mechanical defect caused early termination at 17 days of the first in vivo study, but two subsequent implants proceeded without complication and electively terminated at 30 and 70 days. Serum chemistries and plasma free hemoglobin were within normal limits. Gross necropsy revealed small, subclinical infarctions in the kidneys of the 30 and 70 day animals (confirmed by histopathology). The results of these experiments, particularly the biocompatibility demonstrated in vivo encourage further development of a miniature magnetically levitated VAD for the pediatric population. Ongoing work including further reduction of size will lead to a design freeze in preparation for of clinical trials.