In-Vivo Evaluation of a Novel Integrated Pediatric Pump Lung in a 30 Day Ovine Animal Model.

Recently there has been increased use of mechanical circulatory support in pediatric patients as a bridge to cardiopulmonary recovery or transplantation. However, there are few devices that are optimized and approved for use in pediatric patients. We designed and prototyped a novel integrated pediatric pump lung (PPL) that underwent 30 day in-vivo testing in seven juvenile Dorset Hybrid sheep. Devices were implanted in a right atrial to pulmonary artery configuration. Six of seven sheep survived with a device functioning for 25-35 days. The device flow rate was maintained at 2.08 ± 0.34 to 2.54 ± 0.16 L/min with oxygen transfer of 109.8 ± 24.8 to 151.2 ± 26.2 ml/min over the study duration. Aside from a postoperative drop in hematocrit, all hematologic and blood chemistry test values returned to normal ranges after 1-2 weeks postoperatively. Similarly, lactate dehydrogenase increased postoperatively and returned to baseline. In two sheep, there were early device failures due to oxygenator thrombosis on postoperative days zero and five; they then had oxygenator exchanges with subsequent devices performing stably for 30 days. This study demonstrated that the integrated PPL device exhibited stable performance and acceptable biocompatibility in a 30 day ovine model.

Ex vivo lung perfusion in donation after circulatory death: A post hoc analysis of the Normothermic Ex Vivo Lung Perfusion as an Assessment of Extended/Marginal Donors Lungs trial.

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multicenter setting. METHODS: This was an unplanned post hoc analysis of a multicenter, prospective, nonrandomized trial that took place during 2011 to 2017 with 3 years of follow-up. Patients were placed into 3 groups based off procurement strategy: brain-dead donor (control), brain-dead donor evaluated by EVLP, and DCD donors evaluated by EVLP. The primary outcomes were severe primary graft dysfunction at 72 hours and survival. Secondary outcomes included select perioperative outcomes, and 1-year and 3-years allograft function and quality of life measures. RESULTS: The DCD EVLP group had significantly higher incidence of severe primary graft dysfunction at 72 hours (P = .03), longer days on mechanical ventilation (P < .001) and in-hospital length of stay (P = .045). Survival at 3 years was 76.5% (95% CI, 69.2%-84.7%) for the control group, 68.3% (95% CI, 58.9%-79.1%) for the brain-dead donor group, and 60.7% (95% CI, 45.1%-81.8%) for the DCD group (P = .36). At 3-year follow-up, presence observed bronchiolitis obliterans syndrome or quality of life metrics did not differ among the groups. CONCLUSIONS: Although DCD EVLP allografts might not be appropriate to transplant in every candidate recipient, the expansion of their use might afford recipients stagnant on the waitlist a viable therapy.

Physiological Basis for Xenotransplantation from Genetically-Modified Pigs to Humans: A Review.

The collective efforts of scientists over multiple decades have led to advancements in molecular and cellular biology-based technologies including genetic engineering and animal cloning, that are now being harnessed to enhance the suitability of pig organs for xenotransplantation into humans. Using organs sourced from pigs with multiple gene deletions and human transgene insertions, investigators have overcome formidable immunological and physiological barriers in pig-to-non-human primate (NHP) xenotransplantation and achieved prolonged pig xenograft survival. These studies informed the design of Revivicor's (Revivicor Inc, Blacksburg, VA) genetically engineered pig with 10 genetic modifications (10 GE) (including the inactivation of 4 endogenous porcine genes and insertion of 6 human transgenes) whose hearts and kidneys have now been studied in preclinical human xenotransplantation models using brain-dead recipients. Additionally, the first two clinical cases of pig-to-human heart xenotransplantation were recently performed using hearts from this 10 GE pig at the University of Maryland. While this review focuses on xenotransplantation of hearts and kidneys, multiple organs, tissues, and cell-types from genetically engineered pigs will provide much-needed therapeutic interventions in the future.

Computational fluid dynamics-based design and in vitro characterization of a novel pediatric pump-lung.

BACKGROUND: Although extracorporeal membrane oxygenation (ECMO) has been used to provide temporary support for pediatric patients suffering severe respiratory or cardiac failure since 1970, ECMO systems specifically designed for pediatric patients, particularly for long-term use, remain an unmet clinical need. We sought to develop a new pediatric ECMO system, that is, pediatric pump-lung (PPL), consisting of a unique cylinder oxygenator with an outside-in radial flow path and a centrifugal pump. METHODS: Computational fluid dynamics was used to analyze the blood fluid field for optimized biocompatible and gas exchange performances in terms of flow characteristics, hemolysis, and gas transfer efficiency. Ovine blood was used for in vitro hemolysis and gas transfer testing. RESULTS: Both the computational and experimental data showed that the pressure drop through the PPL's oxygenator is significantly low, even at a flow rate of more than 3.5 L/min. The PPL showed better hemolysis performance than a commercial ECMO circuit consisting of the Quadrox-iD pediatric oxygenator and the Rotaflow pump at a 3.5 L/min flow rate and 250 mm Hg afterload pressure. The oxygen transfer rate of the PPL can reach over 200 mL/min at a flow rate of 3.5 L/min. CONCLUSIONS: The PPL has the potential to provide adequate blood pumping and excellent respiratory support with minimal risk of hemolysis for a wide range of pediatric patients.

Pulmonary thromboendarterectomy in hospitalized versus elective patients with chronic thromboembolic pulmonary hypertension.

OBJECTIVE: We sought to characterize outcomes in patients undergoing pulmonary thromboendarterectomy electively versus after acute presentation. METHODS: This is a retrospective analysis of patients who underwent pulmonary thromboendarterectomy from October 2015 to April 2022. Patients were divided into 2 groups depending on elective surgery or surgery during the same hospitalization as their presentation. RESULTS: In total, 69 patients were included: 45 in the hospitalized group and 24 in the elective group. Patients in the hospitalized group were less likely to have chronic lung disease, history of pulmonary embolism and hypertension, be on anticoagulation and medication for pulmonary hypertension, and present with >1 month of respiratory symptoms. They were more likely to have worse preoperative right ventricular function. Among other demographics, risk factors for venous thromboembolism were similar between both groups. Thirteen patients in the hospitalized group required preoperative extracorporeal membrane oxygenation. There was no difference in disease classification and operative, cardiopulmonary bypass, and hypothermic circulatory arrest durations between both groups. Postoperative complications were similar between both groups, except for greater frequency of deep vein thrombosis in the hospitalized group (26.7% vs 4.2%, P = .03). In-hospital and intensive care unit length of stay were similar between both groups. Overall, in-hospital mortality was 4.3% and was similar between both groups; P = .28. CONCLUSIONS: Our series shows that pulmonary thromboendarterectomy can be safely performed in patients presenting acutely, with comparable postoperative complications and in-hospital mortality to an elective setting. Such patients present with worse right ventricular function, sometimes requiring temporary mechanical support.

Investigation of the role of von Willebrand factor in shear-induced platelet activation and functional alteration under high non-physiological shear stress.

BACKGROUND: von Willebrand factor (vWF) plays a crucial role in physiological hemostasis through platelet and subendothelial collagen adhesion. However, its role in shear-induced platelet activation and functional alteration under non-physiological conditions common to blood-contacting medical devices (BCMDs) is not well investigated. METHODS: Fresh healthy human blood was treated with an anti-vWF antibody to block vWF-GPIbα interaction. Untreated blood was used as a control. They were exposed to three levels of non-physiological shear stress (NPSS) (75, 125, and 175 Pa) through a shearing device with an exposure time of 0.5 s to mimic typical shear conditions in BCMDs. Flow cytometric assays were used to measure the expression levels of PAC-1 and P-Selectin and platelet aggregates for platelet activation and the expression levels of GPIbα, GPIIb/IIIa, and GPVI for receptor shedding. Collagen/ristocetin-induced platelet aggregation capacity was characterized by aggregometry. RESULTS: The levels of platelet activation and aggregates increased with increasing NPSS in the untreated blood. More receptors were lost with increasing NPSS, resulting in a decreased capacity of collagen/ristocetin-induced platelet aggregation. In contrast, the increase in platelet activation and aggregates after exposure to NPSS, even at the highest level of NPSS, was significantly lower in treated blood. Nevertheless, there was no notable difference in receptor shedding, especially for GPIIb/IIIa and GPVI, between the two blood groups at the same level of NPSS. The block of vWF exacerbated the decreased capacity of collagen/ristocetin-induced platelet aggregation. CONCLUSIONS: High NPSS activates platelets mainly by enhancing the vWF-GPIbα interaction. Platelet activation and receptor shedding induced by high NPSS likely occur through different pathways.

Increased phagocytosis capacity of circulating neutrophils in patients on continuous flow ventricular assist device support.

BACKGROUND: Neutrophils take part in the innate immune response, phagocytosis, and pro-inflammatory cytokine release. The phagocytic capacity of circulating neutrophils in patients on continuous flow (CF) ventricular assist device (VAD) has not been well studied. METHODS: Blood samples from 14 patients undergoing CF-VAD implantation were collected and analyzed preoperatively (at baseline) and on postoperative days (POD) 3, 7, 14, and 28. Flow cytometry was used to assess the surface expression levels of CD62L, CD162, and macrophage antigen-1 (MAC-1) and neutrophil phagocytic capacity. Interleukin 1 (IL1), IL6, IL8, TNF-α, neutrophil elastase, and myeloperoxidase in plasma were measured using enzyme-linked immunosorbent assays. RESULTS: Among the 14 patients, seven patients had preoperative bridge device support. Relative to baseline, patients with no bridge device had elevated leukocyte count and neutrophil elastase by POD3 which normalized by POD7. Neutrophil activation level, IL6, IL8, and TNF-α increased by POD3 and sustained elevated levels for 7-14 days postoperatively. Elevated neutrophil phagocytic capacity persisted even until POD28. Similar patterns were observed in patients on a preoperative bridge device. CONCLUSIONS: Neutrophil activation and phagocytic capacity increased in response to VAD support, while inflammatory cytokines remain elevated for up to 2 weeks postoperatively. These findings may indicate that VAD implantation elicits circulating neutrophils to an abnormal preemptive phagocytotic phenotype.

Indexed donor cardiac output for improved size matching in heart transplantation: A United Network for Organ Sharing database analysis.

Objective: Implantation of an appropriately sized donor heart is critical for optimal outcomes after heart transplantation. Although predicted heart mass has recently gained consideration, there remains a need for improved granularity in size matching, particularly among small donor hearts. We sought to determine if indexed donor cardiac output is a sensitive metric to assess the adequacy of a donor heart for a given recipient. Methods: A retrospective analysis was performed (2003-2021) in isolated orthotopic heart transplant recipients from the United Network for Organ Sharing database. Donor cardiac output was divided by recipient body surface area to compute cardiac index (donor cardiac index). Predicted heart mass ratio was computed as donor/recipient predicted heart mass. The primary outcome was mortality 1 year after transplant. Results: Among transplant recipients, median donor cardiac output was 7.3 (5.8-9.0) liters per minute and donor cardiac index was 3.7 (3.0-4.6) liters per minute/m2. Predicted heart mass ratio was 1.01 (0.91-1.13). After multivariable adjustment, higher donor cardiac index was associated with lower 1-year mortality risk (odds ratio, 0.92, P = .042). Recipients with predicted heart mass ratio less than 0.80 (n = 255) had a lower median donor cardiac index than those with a predicted heart mass ratio of 0.80 or greater (3.2 vs 3.7, P < .001). As predicted, heart mass ratio became smaller and the association between donor cardiac index and 1-year mortality became progressively stronger. Conclusions: Higher donor cardiac index was associated with a lower probability of 1-year mortality among patients undergoing heart transplantation and served to further quantify mortality risk among those with a small predicted heart mass ratio. Donor cardiac index appears to be an effective tool for size matching and may serve as an adjunctive strategy among small donor hearts with a low predicted heart mass ratio.

Graft dysfunction in compassionate use of genetically engineered pig-to-human cardiac xenotransplantation: a case report.

BACKGROUND: A genetically engineered pig cardiac xenotransplantation was done on Jan 7, 2022, in a non-ambulatory male patient, aged 57 years, with end-stage heart failure, and on veno-arterial extracorporeal membrane oxygenation support, who was ineligible for an allograft. This report details our current understanding of factors important to the xenotransplantation outcome. METHODS: Physiological and biochemical parameters critical for the care of all heart transplant recipients were collected in extensive clinical monitoring in an intensive care unit. To ascertain the cause of xenograft dysfunction, we did extensive immunological and histopathological studies, including electron microscopy and quantification of porcine cytomegalovirus or porcine roseolovirus (PCMV/PRV) in the xenograft, recipient cells, and tissue by DNA PCR and RNA transcription. We performed intravenous immunoglobulin (IVIG) binding to donor cells and single-cell RNA sequencing of peripheral blood mononuclear cells. FINDINGS: After successful xenotransplantation, the graft functioned well on echocardiography and sustained cardiovascular and other organ systems functions until postoperative day 47 when diastolic heart failure occurred. At postoperative day 50, the endomyocardial biopsy revealed damaged capillaries with interstitial oedema, red cell extravasation, rare thrombotic microangiopathy, and complement deposition. Increased anti-pig xenoantibodies, mainly IgG, were detected after IVIG administration for hypogammaglobulinaemia and during the first plasma exchange. Endomyocardial biopsy on postoperative day 56 showed fibrotic changes consistent with progressive myocardial stiffness. Microbial cell-free DNA testing indicated increasing titres of PCMV/PRV cell-free DNA. Post-mortem single-cell RNA sequencing showed overlapping causes. INTERPRETATION: Hyperacute rejection was avoided. We identified potential mediators of the observed endothelial injury. First, widespread endothelial injury indicates antibody-mediated rejection. Second, IVIG bound strongly to donor endothelium, possibly causing immune activation. Finally, reactivation and replication of latent PCMV/PRV in the xenograft possibly initiated a damaging inflammatory response. The findings point to specific measures to improve xenotransplant outcomes in the future. FUNDING: The University of Maryland School of Medicine, and the University of Maryland Medical Center.

Partial heart xenotransplantation: A research protocol in non-human primates.

Partial heart transplantation is a new type of transplant that delivers growing heart valve replacements for babies. Partial heart transplantation differs from orthotopic heart transplantation because only the part of the heart containing the heart valve is transplanted. It also differs from homograft valve replacement because viability of the graft is preserved by tissue matching, minimizing donor ischemia times, and recipient immunosuppression. This preserves partial heart transplant viability and allows the grafts to fulfill biological functions such as growth and self-repair. These advantages over conventional heart valve prostheses are balanced by similar disadvantages as other organ transplants, most importantly limitations in donor graft availability. Prodigious progress in xenotransplantation promises to solve this problem by providing an unlimited source of donor grafts. In order to study partial heart xenotransplantation, a suitable large animal model is important. Here we describe our research protocol for partial heart xenotransplantation in nonhuman primates.

Neutrophil Structural and Functional Alterations After High Mechanical Shear Stress Exposure.

Patients on mechanical circulatory support are prone to infections, increasing morbidity and mortality. These circulatory support devices generate high mechanical shear stress (HMSS) that can causes trauma to blood. When leukocytes become damaged, their immune response function may be impaired or weakened, leading to increased infection vulnerability. This study examined neutrophil structural and functional alterations after exposure to 75, 125, and 175 Pa HMSS for 1 second. Human blood was exposed to three levels of HMSS using a blood shearing device. Neutrophil morphological alteration was characterized by examining blood smears. Flow cytometry assays were used to analyze expression levels of CD62L and CD162 receptors, activation level (CD11b), and aggregation (platelet-neutrophil aggregates). Neutrophil phagocytosis and rolling were examined via functional assays. The results show neutrophil structure (morphology and surface receptors) and function (activation, aggregation, phagocytosis, rolling) were significantly altered after HMSS exposure. These alterations include cell membrane damage, loss of surface receptors (CD62L and CD162), initiation of activation and aggregation, upregulation of phagocytic ability and increased rolling speed. The alterations were the most severe after 175 Pa exposure. HMSS caused damage and activation of neutrophils, potentially impairing normal neutrophil function, leading to weakened immune defense and increasing a patient's vulnerability to infections.

Cardiac surgery in acute heparin-induced thrombocytopenia managed with therapeutic plasma exchange and intravenous immunoglobulin.

Background: Urgent surgery requiring heparin exposure during cardiopulmonary bypass can be challenging in patients with acute heparin-induced thrombocytopenia (HIT). The use of treatments such as therapeutic plasma exchange (TPE) to remove HIT antibodies and intravenous immunoglobulin (IVIg) to antagonize HIT antibody-mediated platelet activation are increasingly reported in patients who undergo cardiac surgery. The optimal treatment approach to mitigate the risks of heparin administration in this situation is not known. Key Clinical Question: Can TPE coupled to IVIg allow for safe heparin exposure in patients with HIT? Clinical Approach: TPE and IVIg were used to enable heparin exposure for surgical placement of a left ventricular assist device in a patient with HIT. Serial patient samples were tested in antigen-based and functional HIT assays. Conclusion: Dissociation between antigen-based (enzyme-linked immunosorbent assay) and functional (serotonin release assay) testing was noted, and TPE coupled to IVIg was associated with an excellent clinical response.

Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. DESIGN: This study was a case series. SETTING: This study was performed at a single institution in a University setting. PARTICIPANTS: Patients requiring prolonged VA-ECMO were included. INTERVENTIONS: No interventions were done. This was an observational study. MEASUREMENTS AND MAIN RESULTS: Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. CONCLUSIONS: An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute.

Intraoperative Management of an Orthotopic Porcine-to-Human Cardiac Xenotransplant.

We report the intraoperative management of an orthotopic cardiac xenotransplant in a 57-year-old man with nonischemic cardiomyopathy requiring venoarterial extracorporeal membrane oxygenation. Transesophageal echocardiography was used for preharvest assessment. Continuous ex vivo perfusion of the heart was performed. Steps were taken to avoid potential xenozoonosis transmission to other patients and staff. Preclinical experience guided our intraoperative management in controlling hemodynamics and using prophylactic antiarrhythmic medications. Echocardiography aided in the diagnosis of aortic dissection in the patient after transplant. Intraoperative cardiac function was excellent. The patient was weaned from all mechanical support 4 days after transplant.

A Standardized Approach to Orthotopic (Life-supporting) Porcine Cardiac Xenotransplantation in a Nonhuman Primate Model.

Cardiac xenotransplantation from swine has been proposed to "bridge the gap" in supply for heart failure patients requiring transplantation. Recent preclinical success using genetically modified pig donors in baboon recipients has demonstrated survival greater than 6 mo, with a modern understanding of xenotransplantation immunobiology and continued experience with large animal models of cardiac xenotransplantation. As a direct result of this expertise, the Food and Drug Administration approved the first in-human transplantation of a genetically engineered cardiac xenograft through an expanded access application for a single patient. This clinical case demonstrated the feasibility of xenotransplantation. Although this human study demonstrated proof-of-principle application of cardiac xenotransplantation, further regulatory oversight by the Food and Drug Administration may be required with preclinical trials in large animal models of xenotransplantation with long-term survival before approval of a more formalized clinical trial. Here we detail our surgical approach to pig-to-primate large animal models of orthotopic cardiac xenotransplantation, and the postoperative care of the primate recipient, both in the immediate postoperative period and in the months thereafter. We also detail xenograft surveillance methods and common issues that arise in the postoperative period specific to this model and ways to overcome them. These studies require multidisciplinary teams and expertise in orthotopic transplantation (cardiac surgery, anesthesia, and cardiopulmonary bypass), immunology, genetic engineering, and experience in handling large animal donors and recipients, which are described here. This article serves to reduce the barriers to entry into a field with ever-growing enthusiasm, but demands expertise knowledge and experience to be successful.

The Jarvik 2000 Left Ventricular Assist Device: Results of the United States Bridge to Transplant Trial.

The Jarvik 2000 bridge to transplant investigational device exemption study was a multicentered, prospective study of 150 UNOS status I patients implanted with the Jarvik 2000 between 2005 and 2012. During the study period, there were numerous modifications of the system that included converting from pin to cone bearings. Results were analyzed for three cohorts: total (n = 150), pin (n = 128), and cone (n = 22). Baseline demographics included age (52 ± 13), gender (79% male), size (BSA 1.98), and etiology (37% idiopathic dilated cardiomyopathy; 43% Ischemic). Seventy percent of patients were either INTERMACS 1 or 2. The primary endpoint-defined as successful transplantation or listing at 180 days (prespecified at 65%; 95% lower CI: 57%)-was successfully achieved for the total cohort (67.3%; 95% CI: 59.5%-74.3%; p = 0.006). In subgroup analysis of the more contemporary, cone-bearing group, the primary endpoint was met in 91% (95% CI: 72%-97.5%; p = 0.001). Compared with pin patients, cone-bearing patients had less hemolysis as well as decreased end-organ dysfunction. Functional and quality of life scores improved after implantation independent type of bearing. In conclusion, despite a particularly sick patient population, the Jarvik 2000 was shown to be effective in supporting the advanced HF patient.

The road to the first FDA-approved genetically engineered pig heart transplantation into human.

We have been testing genetically engineered (GE) pig hearts and optimizing immunosuppression (IS) in non-human primates (NHPs) since 2005. We demonstrate how we translated this preclinical investigation into a US Food and Drug Administration (FDA)-approved clinical cardiac xenotransplantation. First, genetically engineered (GE) pig hearts were transplanted into the abdomen of NHP along with IS, which included anti-CD20 and anti-CD40-based co-stimulation blockade antibodies. We reported 945 days of survival of three gene GE pig hearts in NHPs. Building on this proof-of-concept, we tested 3-10 gene-modified GE pig hearts (in order to improve the immunocompatibility of the xenograft further) in a life-supporting orthotopic model, but had limited success due to perioperative cardiac xenograft dysfunction (PCXD). With novel non-ischemic continuous perfusion preservation (NICP), using the XVIVO Heart solution (XHS), life-supporting survival was extended to 9 months. We approached the FDA under an application for "Expanded Access" (EA), to transplant a GE pig heart in a patient with end-stage non-ischemic cardiomyopathy. He was without other therapeutic options and dependent on VA-ECMO. A team of FDA reviewers reviewed our preclinical research experience and data and allowed us to proceed. This clinical cardiac xenotransplantation was performed, and the patient survived for 60 days, demonstrating the translational preclinical investigation of cardiac xenotransplantation from bench to bedside. The ultimate etiology of graft failure is currently a topic of investigation and lessons learned will progress the field forward.

Computational fluid dynamics analysis and experimental hemolytic performance of three clinical centrifugal blood pumps: Revolution, Rotaflow and CentriMag.

Centrifugal blood pumps have become popular for adult extracorporeal membrane oxygenation (ECMO) due to their superior blood handling and reduced thrombosis risk featured by their secondary flow paths that avoid stagnant areas. However, the high rotational speed within a centrifugal blood pump can introduce high shear stress, causing a significant shear-induced hemolysis rate. The Revolution pump, the Rotaflow pump, and the CentriMag pump are three of the leading centrifugal blood pumps on the market. Although many experimental and computational studies have focused on evaluating the hydraulic and hemolytic performances of the Rotaflow and CentriMag pumps, there are few on the Revolution pump. Furthermore, a thorough direct comparison of these three pumps' flow characteristics and hemolysis is not available. In this study, we conducted a computational and experimental analysis to compare the hemolytic performances of the Revolution, Rotaflow, and CentriMag pumps operating under a clinically relevant condition, i.e., the blood flow rate of 5 L/min and pump pressure head of 350 mmHg, for adult ECMO support. In silico simulations were used to characterize the shear stress distributions and predict the hemolysis index, while in vitro blood loop studies experimentally determined hemolysis performance. Comparative simulation results and experimental data demonstrated that the CentriMag pump caused the lowest hemolysis while the Revolution pump generated the highest hemolysis.

Anatomical Differences Between Human and Pig Hearts and Their Relevance for Cardiac Xenotransplantation Surgical Technique.

Cardiac xenotransplantation has been proposed to bridge the gap between supply and demand for patients with end-stage heart failure requiring transplantation. However, differences in pig anatomy compared with human anatomy require modification of the surgical approach. In addition, careful consideration should be given to size matching before transplantation. (Level of Difficulty: Advanced.).