Artificial organs最新文献

Background: Predicting hemolysis numerically based on the power-law model using idealized coefficients obtained from simplified devices yields a large variability in hemolysis index predictions. A computational fluid dynamics (CFD)-based Kriging surrogate modeling approach, developed by Craven et al. at the US Food & Drug Administration (FDA), was applied to a Fontan cavopulmonary assist device (CPAD) to generate device-specific hemolysis power-law coefficients.

Methods: The hemolysis index of a CPAD was measured using tests in a mock loop and simulated using CFD. The Kriging surrogate modeling approach was employed for the Lagrangian and Eulerian formulations of the stress-based hemolysis power-law model. The CPAD-specific power-law coefficients obtained from one design of the CPAD were used in predicting the Modified Index of Hemolysis (MIH) for an alternate design of the CPAD.

Results: The MIH CFD predictions with the CPAD-specific coefficients deviate by 16%-20% using the Eulerian approach, and 7%-15% using the Lagrangian approach, compared with experimental results for the alternate design. This vastly improves over the use of idealized empirical coefficients, which yield variation in MIH predictions up to two orders of magnitude.

Conclusion: The presented power-law approach shows good correlation between CFD and tests in predicting MIH for CPAD design modifications. The hemolysis power-law coefficients obtained in this study may be useful in predicting hemolysis in similar rotary blood pumps.

The American Transplant Congress (ATC) 2024, held in Philadelphia, serves as a vital platform for unveiling new research and clinical experience in organ machine perfusion—a key area in organ transplantation. This year's congress gathered 4652 participants from 49 countries, including top experts, to spotlight innovations in machine perfusion across various organ types, such as the liver, kidney, heart, and lung. A total of 87 abstracts on organ machine perfusion were presented. We selected 39 abstracts that showed advances including new approaches to organ preservation, promising treatments and biomarkers, cellular therapy, and novel research areas. ATC 2024 underscored major advancements in machine perfusion in both experimental and clinical studies and demonstrated its role as a disruptive force in enhancing transplant outcomes and expanding the donor pool, fostering a robust exchange of knowledge on a global scale.

Background: Normothermic machine perfusion (NMP) is increasingly used to preserve and assess donor livers prior to transplantation. Due to its success, it is expected that more centers will start using this technology. However, NMP may also cause adverse effects.

Methods: In this retrospective, observational study, we investigated the effect of NMP pressures on donor liver weight, post-transplant outcomes, and hepatic perfusion characteristics. A total of 36 livers were transplanted after NMP. NMP perfusion pressure settings were lowered from a median (IQR) of 47 mmHg (42-54) to 34 mmHg (30-39) for the hepatic artery (HA), and from 8 mmHg (7-10) to 7 mmHg (6-8) for the portal vein (PV) to diminish potential edema formation inside the liver.

Results: This change appeared to lead to a reduction of liver weight after NMP (-22 g to -143 g, p = 0.02), without affecting the PV flow velocity (35.5 to 48.0 cm/s, p = 0.54), or hepatocellular injury markers during NMP (AST 1511-1148 U/L, p = 0.44; ALT 318-849 U/L, p = 0.35), and post-transplantation outcomes. Changes in liver weight correlated significantly with the applied PV pressure during NMP (r = 0.52, p < 0.01) and the HA flow (r = 0.38, p < 0.05).

Conclusion: NMP can lead to a reduction in liver weight, which might be masked by edema when high perfusion pressures are used. We encourage applying the lowest perfusion pressures possible to reach adequate flows and oxygen supply during liver NMP.

Background: Liver disease is a growing burden. Transplant organs are scarce. Extracorporeal liver support systems (ELSS) are a bridge to transplantation for eligible patients. For transplant-ineligible patients the objective becomes liver recovery.

Methods: We review seven decades of non-cell-based ELSS research in humans. Where possible, we emphasize randomized controlled trials (RCTs). When RCTs are not available, we describe the available human clinical data.

Results: There are three broad cell-free approaches to remove protein-bound toxins (PBTs) and treat liver failure. The first is a dialysate binder suspension. A material that binds the PBT (the binder) is added to the dialysate. Binders include albumin, charcoal, and polystyrene sulfonate sodium. The unbound fraction of the PBT crosses the dialyzer membrane along a chemical gradient and binds to the binder. The second approach is using grains of sorbent fixed in a plastic housing to remove PBTs. Toxin-laden blood or plasma flows directly through the column. Toxins are removed by binding to the sorbent. The third approach is exchanging toxin-laden blood, or fractions of blood, for a healthy donor blood product. Most systems lack widespread acceptance, but plasma exchange (PE) is recommended in many guidelines. The large donor plasma requirement of PE creates demand for systems to complement or replace it.

Conclusions: Now that PE has become recommended in some, but not all, jurisdictions, we discuss the importance of reporting precise PE protocols and dose. Our work provides an overview of promising new systems and lessons from old technologies to enable ELSS improvement.

Background: Machine perfusion is a promising strategy for safeguarding liver transplants donated after cardiac death (DCD). In this study, we developed and validated a novel machine perfusion approach for mitigating risk factors and salvaging severe DCD livers.

Methods: A novel hypothermic oxygenated perfusion (HOPE) system was developed, incorporating two pumps and an elastic water sac to emulate the functionality of the cardiac cycle. Compared to conventional systems (HOPE S1 and S2), the novel HOPE system (HOPE S3) was evaluated in rats, utilizing healthy livers perfused with methylene blue diluted using Histidine-tryptophan-ketoglutarate (HTK) solution or DCD livers subjected to 60 min of warm ischemia without heparin administration. Liver perfusion outcomes were assessed through macroscopic and microscopic evaluations, molecular analyses, and orthotopic liver transplantation (OLT).

Results: DCD livers subjected to HOPE systems' perfusion exhibited decreased injury and enhanced survival rates compared to static cold storage following 60 min of warm ischemia (DCD + SCS). The 4-week post-transplantation survival rates were 0%, 20%, and 33% in the DCD + SCS, HOPE S1, and HOPE S2 groups, respectively. HOPE S3 conferred protection against hepatocyte and non-parenchymal cell injury, resulting in a 67% animal survival rate following 60 min of warm donor ischemia (HOPE S3). Assessments of hepatic sinusoidal microcirculation, morphological changes, and molecular alterations in preserved livers further confirmed these findings.

Conclusions: The newly devised machine perfusion system can enhance and uniform liver perfusion and may become a promising tool for revitalizing DCD liver grafts afflicted with severe warm ischemic injuries.

Objective: To explore the experience of extracorporeal life support (ECLS)-assisted maintenance of brain death donors with extremely unstable hemodynamics.

Methods: We retrospectively analyzed the clinical data of 12 brain-dead donors who received ECLS in our hospital from May 2015 to May 2022 due to extremely unstable hemodynamics. The organ acquisition status was analyzed. The transplant outcome of the livers and kidneys procured from these donors on ECLS was also evaluated, who are currently considered as having extended criteria.

Results: After ECLS, the hemodynamics of these 12 patients quickly stabilized and all completed apnea testing and reached the criteria for brain death. The 12 donors on ECLS contributed 36 organs: 1 heart, 2 lungs, 11 livers, and 22 kidneys. All liver and kidney transplant recipients survived within 1 year after transplantation. The 12-month graft survival rate for these 22 ECLS transplanted kidneys was 95%. Four (18.2%) kidney transplant recipients developed DGF. The average creatinine at discharge was 2.01 ± 0.70 mg/dL (1.14-3.67 mg/dL), which showed a downward trend in the first year after operation. The 12-month graft survival rate for these 11 ECLS transplanted livers was 100%. There was no incidence of primary nonfunction. The transaminase and bilirubin in the liver transplantation recipient group showed a downward trend, with an average total bilirubin of 2.23 ± 0.17 mg/dL (1.93-2.46 mg/dL) and an average alanine aminotransferase level of 46.55 ± 17.45 (33-89 units/L) at the time of discharge.

Conclusions: ECLS can maintain the organ function of potential brain death donors with extremely unstable circulation and does not affect the functional recovery of the graft.