Ischemia-reperfusion injury of the marginal liver under machine perfusion condition: an experimental study in a mouse model

Background: Liver transplantation is the only effective treatment for end-stage liver disease. The shortage of liver grafts has prompted the use of the so-called marginal livers. The usage of ex-vivo normothermic machine perfusion (NMP) improves donor liver function and graft survival (Shen, et al.,2023). NMP is widely adopted to enhance the function of marginal organs, including those from donors after cardiac death (DCD) (Nasralla, et al.,2018). However, many donor livers are still discarded for not matching clinical viability criteria (Liu, et al.,2014). This highlights the need for better preservation strategies and optimized perfusion techniques. Animal models are crucial for understanding the mechanisms of NMP. Rat models are commonly used but have limitations in molecular studies. For this purpose, mouse models are principally more suitable due to the availability of abundant genetically modified strains. These models are ideal for exploring molecular mechanisms for better understanding the beneficial effect of NMP, especially for marginal livers. A well-designed NMP system must support both, grafts obtained from living donors but also from donors after cardiac death. Aim: First, we aimed to establish an ex-vivo NMP model for mouse livers that can sustain 12 hour using grafts from living donors. Second, we aimed to adapt the living donor model to meet the requirements for NMP of DCD grafts. Third, we aimed to utilize the model to evaluate the effects of donor sex, mid-perfusion perfusate replacement, and the addition of an artificial oxygen carrier into the perfusate on liver preservation results.