🎗Hypothermic oxygenated machine perfusion for partial grafts in a porcine model simulating living donor liver transplantation

Introduction: Hypothermic oxygenated machine perfusion (HOPE) has been clinically implemented to improve outcomes in extended criteria donor and donation after circulatory death liver transplantation by mitigating ischemia–reperfusion injury (IRI). In contrast, living donor liver transplantation (LDLT) utilizes partial grafts from healthy donors, and static cold storage (SCS) has generally been considered sufficient. However, graft procurement procedures in LDLT, including parenchymal transection and intermittent vascular occlusion, may induce subclinical molecular injury such as mitochondrial dysfunction and release of damage-associated molecular patterns (DAMPs). The role of HOPE in optimizing preservation of partial grafts in LDLT remains unclear. This study aimed to investigate whether HOPE provides additional benefits using a porcine model simulating LDLT.
Methods: A porcine partial liver graft model simulating LDLT was established. Female pigs (25–30 kg) underwent selective clamping of the Glissonean pedicle supplying the left lateral lobe (15 minutes of clamping followed by 5 minutes of release, repeated four times) to induce localized ischemia while minimizing systemic effects. Partial grafts were procured using the clamp-crush technique and randomly assigned to either HOPE (n = 3) or SCS (n = 3) for 2 hours of preservation. In the HOPE group, grafts were perfused via the portal vein using a machine perfusion system developed in our department, with oxygenated histidine–tryptophan–ketoglutarate solution at 8–12°C and 100% oxygen supplied at 2 L/min. Perfusate high-mobility group box 1 (HMGB1) and flavin mononucleotide (FMN) were analyzed. Statistical comparisons were conducted using the Mann–Whitney U test.
Results: All procedures were successfully completed, and HOPE was stably maintained. At 2 hours, HMGB1 levels were lower in the HOPE group than in the SCS group (46.8 ± 18.1 vs. 275.8 ± 102.6 ng/mL/100 g liver), without statistical significance. When analyzed as changes from baseline over the 2-hour preservation period, HMGB1 levels increased in all SCS grafts, whereas in the HOPE group, one graft showed a decrease and the remaining two exhibited only slight increases. FMN levels were also lower in the HOPE group (3.3 ± 0.3 vs. 5.3 ± 1.2 ng/mL), without statistical significance. No apparent differences were observed in histological or immunohistochemical analyses.
Conclusion: In this porcine model simulating LDLT, the expression of HMGB1 and the levels of FMN, both of which are involved in ischemia–reperfusion injury, were reduced. These findings suggest that HOPE may be useful not only as a rescue strategy for marginal grafts but also as an optimization approach for partial graft preservation in LDLT. Importantly, even in relatively well-preserved grafts, HOPE may contribute to minimizing subclinical injury and improving graft quality, supporting its potential role in refining preservation strategies in LDLT.