Forsøksdyr: Monitoring liver function during ex vivo normothermic machine perfusion for extension of donor organ availability

Godkjenningsdato 14.09.2020

Godkjenningsperiode 01.10.2020-01.10.2024

Worldwide and also in Norway there is shortage of donor livers and many patients die on ever growing waiting lists. On the other-hand side, many organs from potential donors are discarded as they are clinically judged as of too low quality with a high-risk of non-function if transplanted.

In this project, we aim to provide objective measurements to rely on during clinical decision making if an organ should be transplanted or discarded. We will employ livers from experimental pigs, which will be monitored extensively with clinically approved bio-sensors (hypoxia: PCO2 tissue sensors, metabolism: microdialysis, tissue properties: electroimpedance), inflammation and histopathology. We will also evaluate kidneys from the same pig in an additional setup of normothermic machine perfusion for evaluation of kidney machine perfusion setup and immunological CD14 and complement inhibition as treatment prior transplantation, complying with the 3Rs, reducing experimental animal numbers.

Donor organs liver and kidney will experience either hepatic artery ischemia in vivo or cold ischemia during storage for 18-20h in standard preservation fluid. Comparator will be procurement and direct machine perfusion. Normothermic machine perfusion of livers for eight hours and kidneys for 4 hours will be performed ex vivo.

If our interventions and monitoring should reveal objective measurements of liver and kidney function, this protocol could easily be employed into clinical transplantation context as microdialysis and tissue PCO2 biosensors are approved for clinical usage.

Up to 36 pigs will be used for organ and blood donation. The pigs will be anesthetized during the whole period of organ isolation and blood collection. The animal will thereafter immediately be euthanized and liver and kidneys procured. We expect minimal stress of the animals and no pain. Today, replacement for the pig kidney and liver is impossible. Organ function is a primary read-out and for that purpose, we need whole livers and kidneys. We reduce numbers of animals, because we will use both livers and kidneys in studies, which are independent from each other.

Our group has large experience with pig experiments. The researchers also have experience of explantation of human organs and ex vivo machine perfusion, therefore, we expect low number of animals to establish this protocol. The group sizes have however to be large enough not to lose statistical power.