Transplantation has grown exponentially with 4,533 life-saving UK transplants in 2022-23. Static cold storage (SCS), using University of Wisconsin solution (UW) is the gold standard. Despite increasing transplants, demand outstrips supply necessitating use of marginal organs.
Here a novel preservation solution, Leeds solution for abdomen (LS-A) is examined, with SCS and Hypothermic oxygenated machine perfusion (HOPE) applications. A battery of biomarkers: HMBG-1 marker of necrosis; caspase-3 marker of apoptosis; syndecan-1 marker of glycocalyx function and Flavin mitochondrial mononucleotide (FMN) a putative marker of post-transplant function were examined.
This was a pre-clinical, prospective, randomised controlled trial in a porcine model. Normothermic machine perfusion (NMP) simulated the post-transplant milieu. Livers were assigned to LS-A SCS or control (UW or IGL-1).
A proof of principle comparison compared LS-A for both SCS and as a HOPE perfusate with UW for SCS and UW-MPS (UW Machine Perfusion Solution) for HOPE. Livers were interrogated for perfusate blood gases, biochemistry and histology.
50% of SCS LS-A livers met NMP viability criteria versus 0% of controls. LS-A shows significantly lower lactate and potassium. LS-A at 8-hours shows no significant differences from UW at 4-hours. When used for HOPE 40% of LS-A livers met viability criteria whilst no controls did. LS-A and UW-MPS showed no significant differences in lactate, but significantly lower potassium was seen in LS-A HOPE. There were significantly higher levels of apoptosis and necrosis with UW than LS-A in SCS but, no difference in HOPE. FMN showed no correlation with outcome.
This study is the first to show LS-A performed better than UW in marginal organs. No difference existed between LS-A 8-hours versus UW 4-hours SCS. No significant difference exists between LS-A and UW-MPS in HOPE. FMN cannot predict viability, with no correlation between its pre-NMP levels and outcomes. LS-A provides exciting opportunities to improve organ preservation and live animal trials should follow.
