Liver and Hepatocyte Transplantation: What Can Pigs Contribute?

About one-fifth of the population suffers from liver diseases in China, meaning that liver disorders are prominent causative factors relating to the Chinese mortality rate. For patients with end-stage liver diseases such as hepatocellular carcinoma or acute liver diseases with life-threatening liver dysfunction, allogeneic liver transplantation is the only life-saving treatment. Hepatocyte transplantation is a promising alternative for patients with acute liver failure or those considered high risk for major surgery, particularly for the bridge-to-transplant period. However, the lack of donors has become a serious global problem. The clinical application of porcine xenogeneic livers and hepatocytes remains a potential solution to alleviate the donor shortage. Pig grafts of xenotransplantation play roles in providing liver support in recipients, together with the occurrence of rejection, thrombocytopenia, and blood coagulation dysfunction. In this review, we present an overview of the development, potential therapeutic impact, and remaining barriers in the clinical application of pig liver and hepatocyte xenotransplantation to humans and non-human primates. Donor pigs with optimized genetic modification combinations and highly effective immunosuppressive regimens should be further explored to improve the outcomes of xenogeneic liver and hepatocyte transplantation.

Hemolytic Performance in Two Generations of the Sputnik Left Ventricular Assist Device: A Combined Numerical and Experimental Study

Background: Currently, left ventricular assist devices (LVADs) are a successful surgical treatment for patients with end-stage heart failure on the waiting list or with contraindicated heart transplantation. In Russia, Sputnik 1 LVAD was also successfully introduced into clinical practice as a bridge-to-transplant and a destination therapy device. Development of Sputnik 2 LVAD was aimed at miniaturization to reduce invasiveness, optimize hemocompatibility, and improve versatility for patients of various sizes. Methods: We compared hemolysis level in flow path of the Sputnik LVADs and investigated design aspects influencing other types of blood damage, using predictions of computational fluid dynamics (CFD) and experimental assessment. The investigated operating point was a flow rate of 5 L/min and a pressure head of 100 mm Hg at an impeller rotational speed of 9100 min−1. Results: Mean hemolysis indices predicted with CFD were 0.0090% in the Sputnik 1 and 0.0023% in the Sputnik 2. Averaged values of normalized index of hemolysis obtained experimentally for the Sputnik 1 and the Sputnik 2 were 0.011 ± 0.003 g/100 L and 0.004 ± 0.002 g/100 L, respectively. Conclusions: Obtained results indicate obvious improvements in hemocompatibility and sufficiently satisfy the determined miniaturization aim for the Sputnik 2 LVAD development.

MitraClip® procedure as bridge to left ventricular assist device: Enable extracorporeal membrane oxygenation weaning and reduce perioperative risk

Secondary mitral valve regurgitation is a frequent consequence of left ventricular dysfunction in patients with severe heart failure. The management of this disease can be challenging since it often culminates in refractory pulmonary edema and multi-organ failure. We present the case of a 50-year-old male who was admitted in cardiogenic shock following myocardial infarction. After successful revascularization, percutaneous mitral valve repair using the MitraClip® device enabled weaning from extracorporeal membrane oxygenation followed by the implantation of a left ventricular assist device as bridge to transplant.

A Review of Pulmonary Arterial Hypertension Treatment in Extracorporeal Membrane Oxygenation: A Case Series of Adult Patients

Background: Little data is published describing the use of medications prescribed for pulmonary arterial hypertension (PAH) in patients receiving extracorporeal membrane oxygenation (ECMO). Even though many patients with PAH may require ECMO as a bridge to transplant or recovery, little is reported regarding the use of PAH medications in this setting. Methods: This retrospective case series summarizes the clinical experience of 8 patients with PAH receiving ECMO and reviews medication management in the setting of ECMO. Results: Eight PAH patients, 5 of whom were female, ranging in age from 21 to 61 years old, were initiated on ECMO. Veno-arterial (VA) ECMO was used in 4 patients, veno-venous (VV) ECMO and hybrid ECMO configurations in 2 patients respectively. Common indications for ECMO included cardiogenic shock, bridge to transplant, and cardiac arrest. All patients were on intravenous (IV) prostacyclin therapy at baseline. Refractory hypotension was noted in 7 patients of whom 5 patients required downtitration or discontinuation of baseline PAH therapies. Three patients had continuous inhaled epoprostenol added during their time on ECMO. In patients who were decannulated from ECMO, PAH therapies were typically resumed or titrated back to baseline dosages. One patient required no adjustment in PAH therapy while on ECMO. Two patients were not able to be decannulated from ECMO. Conclusion: The treatment of critically ill PAH patients is challenging given a variety of factors that could affect PAH drug concentrations. In particular, PAH patients on prostacyclin analogues placed on VA ECMO appear to have pronounced systemic vasodilation requiring vasopressors which is alleviated by temporarily reducing the intravenous prostacyclin dose. Patients should be closely monitored for potential need for rapid titrations in prostacyclin therapy to maintain hemodynamic stability.

Kasai Procedure in Patients Older Than 90 Days: Worth a Cut

Introduction Age at Kasai portoenterostomy (KPE) has been identified as a predictive factor for native-liver survival in patients with biliary atresia (BA). Outcomes of pediatric liver transplantation (LT) have improved over recent years. It has been proposed to consider primary LT as a treatment option for late-presenting BA infants instead of attempting KPE. We present our experience with patients older than 90 days undergoing KPE. Materials and Methods A retrospective chart review of patients with BA undergoing KPE at our institution between January 2010 and December 2020 was performed. Patients 90 days and older at the time of surgery were included. Patients' characteristics, perioperative data, and follow-up results were collected. Eleven patients matched the inclusion criteria. Mean age at KPE was 108 days (range: 90–133 days). Results Postoperative jaundice clearance (bilirubin < 2 mg/dL) at 2-year follow-up was achieved in three patients (27%). Eight patients (73%) received a liver transplant at a mean of 626 days (range: 57–2,109 days) after KPE. Four patients (36%) were transplanted within 12 months post-KPE. Two patients died 237 and 139 days after KPE due to disease-related complications. One patient is still alive with his native liver, currently 10 years old. Conclusion Even when performed at an advanced age, KPE can help prolong native-liver survival in BA patients and offers an important bridge to transplant. In our opinion, it continues to represent a viable primary treatment option for late-presenting infants with BA.

Experimental Hemodynamics within the Penn State Fontan Circulatory Assist Device

For children born with a single functional ventricle, the Fontan operation bypasses the right ventricle by forming a four-way total cavopulmonary connection adapting the existing ventricle for the systemic circulation. However, upon adulthood, many Fontan patients exhibit low cardiac output and elevated venous pressure, eventually requiring a heart transplantation. Despite efforts to develop a Fontan pump or use an existing ventricular assist device for failing Fontan support, there is still no device designed or tested for subpulmonary support. Penn State University is developing a hydrodynamically levitated Fontan circulatory assist device (FCAD) for bridge-to-transplant or destination therapy. The FCAD hemodynamics, at both steady and pulsatile conditions for three pump operating conditions, were quantified using particle image velocimetry to determine the velocity magnitudes and Reynolds normal and shear stresses. Data were acquired at three planes (0 mm and ±25% of the radius) for the inferior and superior vena cavae inlets and the pulmonary artery outlet. The inlets had a blunt velocity profile that became skewed towards the collecting volute as fluid approached the rotor. At the outlet, regardless of the flow condition, a high-velocity jet exited the volute and moved downstream in a helical pattern. Turbulent stresses observed at the volute exit were influenced by the rotor's rotation. Regardless of inlet conditions, the pump demonstrated advantageous behavior for clinical use with a predictable flow field and a low risk of platelet adhesion and hemolysis based on calculated wall shear rates and turbulent stresses, respectively.

391 First CARMAT implantation in Italy: a nurse’s experience

Aims CARMAT is a new fully implantable device that simulates heart function. CARMAT has three characteristics that allow a physiological simulation that is at the top of biomedical engineering: it is blood-compatible for the use of bovine pericardium; it is pulsatile because it has hydraulic pumps that mimic systole and diastole; it is capable of self-regulating with the physiological needs of the patient. CARMAT has four biological valves that allow the intake of cardioaspirin avoiding the use of Coumadin and continuous blood draw. CARMAT also has two hybrid membranes with an internal part formed by bovine pericardium and an external polyurethane membrane; CARMAT has self-regulation sensors that adapt the system to the patient’s efforts. The operation is relatively simple because the rollers placed inside move the silicondressingstely and so it pushes the walls creating systole and diastole not synchronously as it normally happens but asynchronously, one ventricle at a time. Evaluation of the patient’s haemodynamics, monitoring of vital parameters, dressings of the drive-line, and psychological state. Methods and results Training in the field by the manufacturer due to the absence of material in literature. Since it was the first CARMAT implantation in Italy, we tried to combine experience with the clinical practice of other artificial hearts. The patient was weaned from anesthesia early and extubated; the patient did not show neurological damage. Psychologically, the artificial heart was accepted without any problems by the patient, the drive line had no infections, and the patient was discharged quickly. Conclusions The CARMAT system appears to be the one that best simulates the physiology of the heart because it involves fewer complications than other artificial hearts. This device is used as a bridge to transplant, but research and continuous studies tend to transform it as a therapy to end for patients who leave the transplant list and therefore the possibility of having a heart transplant.