Observations and findings during the development of a subnormothermic/normothermic long-term ex vivo liver perfusion machine.

Background: Ex situliver machine perfusion at subnormothermic/normothermic temperature isincreasingly applied in the field of transplantation to store and evaluateorgans on the machine prior transplantation. Currently, various perfusionconcepts are in clinical and preclinical applications. Over the last 6 years ina multidisciplinary team, a novel blood based perfusion technology wasdeveloped to keep a liver alive and metabolically active outside of the bodyfor at least one week.

Transplantation of a human liver following 3 days of ex situ normothermic preservation.

Current organ preservation methods provide a narrow window (usually <12 hours) to assess, transport and implant donor grafts for human transplantation. Here we report the transplantation of a human liver discarded by all centers, which could be preserved for several days using ex situ normothermic machine perfusion. The transplanted liver exhibited normal function, with minimal reperfusion injury and the need for only a minimal immunosuppressive regimen.

Long-term Normothermic Machine Preservation of Partial Livers: First Experience With 21 Human Hemi-livers.

Objective: The aim of this study was to maintain long-term full function and viability of partial livers perfused ex situ for sufficient duration to enable ex situ treatment, repair, and regeneration.

Background: Organ shortage remains the single most important factor limiting the success of transplantation. Autotransplantation in patients with nonresectable liver tumors is rarely feasible due to insufficient tumor-free remnant tissue.

Synthesis of coagulation factors during long-term ex situ liver perfusion.

Robust viability assessment of grafts during normothermic liver perfusion is a prerequisite for organ use. Coagulation parameters are used commonly for liver assessment in patients. However, they are not yet included in viability assessment during ex situ perfusion.

Sources and prevention of graft infection during long-term ex situ liver perfusion.

Introduction: The use of normothermic liver machine perfusion to repair injured grafts ex situ is an emerging topic of clinical importance. However, a major concern is the possibility of microbial contamination in the absence of a fully functional immune system. Here, we report a standardized approach to maintain sterility during normothermic liver machine perfusion of porcine livers for one week.

FDG-PET/CT: novel method for viability assessment of livers perfused ex vivo.

Purpose: Ex vivo liver machine perfusion is a promising option to rescue marginal liver grafts mitigating the donated organ shortage. Recently, a novel liver perfusion machine that can keep injured liver grafts alive for 1 week ex vivo was developed and reported in Nature Biotechnology. However, liver viability assessment ex vivo is an unsolved issue and the value of 18F-fluorodeoxyglucose (FDG)-PET/CT for such purpose was explored.

Bile formation in long-term ex situ perfused livers.

Background: Long-term ex situ liver perfusion may rescue injured grafts. Little is known about bile flow during long-term perfusion. We report the development of a bile stimulation protocol and motivate bile flow as a viability marker during long-term ex situ liver perfusion.

Hyperoxia in portal vein causes enhanced vasoconstriction in arterial vascular bed.

Long-term perfusion of liver grafts outside of the body may enable repair of poor-quality livers that are currently declined for transplantation, mitigating the global shortage of donor livers. In current ex vivo liver perfusion protocols, hyperoxic blood (arterial blood) is commonly delivered in the portal vein (PV). We perfused porcine livers for one week and investigated the effect of and mechanisms behind hyperoxia in the PV on hepatic arterial resistance.

Automated Insulin Delivery - Continuous Blood Glucose Control During Ex Situ Liver Perfusion.

Objective: With the growing demand for livers in the field of transplantation, interest in normothermic ex situ machine perfusion (NMP) has increased in recent years. This may open the door for novel therapeutic interventions such as repair of suboptimal grafts. For successful long-term NMP of livers, blood glucose (BG) levels need to be maintained in a close to physiological range.

An integrated perfusion machine preserves injured human livers for 1 week.

The ability to preserve metabolically active livers ex vivo for 1 week or more could allow repair of poor-quality livers that would otherwise be declined for transplantation. Current approaches for normothermic perfusion can preserve human livers for only 24 h. Here we report a liver perfusion machine that integrates multiple core physiological functions, including automated management of glucose levels and oxygenation, waste-product removal and hematocrit control.

Model Assisted Analysis of the Hepatic Arterial Buffer Response During Ex Vivo Porcine Liver Perfusion.

Objective: The hepatic arterial buffer response is a well-known phenomenon in hepatic circulation, describing the response of hepatic arterial resistance to changes in portal vein flow. Several vasoactive metabolites underlying its mechanism have been proposed, however, there is currently no clear consensus. The aim of this study is to investigate the hepatic arterial buffer response of porcine livers preserved in a controlled ex vivo perfusion machine.

Perfusion settings and additives in liver normothermic machine perfusion with red blood cells as oxygen carrier. A systematic review of human and porcine perfusion protocols.

Liver machine perfusion (MP) at normothermic temperature (NMP) is a promising way to preserve and evaluate extended criteria donor livers. Currently, no consensus exists in methodology and perfusion protocols. Here, the authors performed a systematic literature search to identify human and porcine studies reporting on liver NMP with red blood cells.