Do not leave the liver hanging

Do not leave the liver hanging: Redesigning the organ chamber to enable long term ex situ liver perfusion

Groen, Puck (TU Delft Mechanical, Maritime and Materials Engineering)

De Jonge, Jeroen (mentor)
Oderwald, Michiel (mentor)
Amelink, Arjen (mentor)
Ottens, M. (graduation committee)

Delft University of Technology
Erasmus Universiteit Rotterdam
Universiteit Leiden

Technical Medicine

2023-05-10

Introduction
The only curative and durable treatment option for patients suffering from end-stage liver disease is liver transplantation. However, there is a shortage of donor grafts of adequate quality, which is a major cause of wait list mortality. Ex situ liver resuscitation, reconditioning or regeneration of sub-optimal donor grafts can potentially enlarge the number of available donor grafts. However, this can only be achieved using long term normothermic machine perfusion (NMP). The current clinically relevant perfusion devices do not fully mimic the in situ environment of the liver, which results in gravity induced pressure injuries and poor peripheral perfusion. The aim of this thesis is to create an organ chamber that is similar to the in situ situation, capable of preventing gravity induced pressure injuries and improving peripheral perfusion.

Materials & Methods
Two prototypes were fabricated using materials bought at the DIY store. Perfusions were performed with porcine (N=3) and human research livers (N=2) using an adapted Liver Assist (XVIVO abdominal) perfusion system. Both prototypes were part of a closed loop perfusion system and in both human research livers all three main vessels were cannulated. Temperature control and perfusion stabilization was tested during perfusion. The water in the reservoir was heated from 20 °C to 37 °C during the first hour, followed by NMP during which the temperature was kept at 37 °C. The influence of the amount of water in the water reservoir on the perfusion parameters was tested by altering the height of the water level. Perfusate samples from the human research livers were taken at set time points.

Results
Both prototypes were capable of controlled rewarming of the liver to 37 °C during the first hour of perfusion. After reaching 37 °C the temperature remained stable. During perfusion with both prototypes, perfusion parameters could be set to the desired target values and the flows remained stable. The second prototype was used to test the effect of different water levels in the water reservoir on the perfusion parameters. With 7 centimeters of water in the reservoir, the portal vein flow was 940 ml/min. With 12 centimeters of water, the portal vein flow started to decrease until it reached a flow of 660 ml/min with the maximum of 23 centimeters of water. The hepatic artery flow was not influenced by the varying water level. The inferior vena cava pressure slowly decreased from 2 mmHg with 7 centimeters of water, to -3 mmHg with 23 centimeters of water. Both perfusions showed an increase in injury markers during perfusion.

Conclusion
In this thesis, a new approach to the organ chamber was explored, to prevent gravity induced pressure injuries and improve peripheral perfusion. Both prototypes were capable of maintaining stable perfusion parameters. The amount of water surrounding the liver influences the flow of the portal vein and the pressure of the inferior vena cava. In the future, this effect could be used to mimic the function of the diaphragm and improve the peripheral perfusion. The next step is to quantify and visualize peripheral perfusion and improve the outcomes of long term liver perfusion.

Liver Transplantation
Machine perfusion
Organ Preservation

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Student theses

master thesis

© 2023 Puck Groen