Mitigating hepatic ischemia and reperfusion injury with polyethylene glycol-enriched Ringer's lactate fluid: insights from an isolated perfused rat model.

BACKGROUND: Cold ischemia-reperfusion (IR) injury is a multifactorial process detrimental to liver graft function during liver transplantation (LT). Although flushing hepatic grafts prior to reperfusion have been well explored, the optimal graft rinse solution to prevent cold IR injury remains largely undefined. The aim of this study was to evaluate whether a new rinse solution combining polyethylene glycol PM 35,000 Da (PEG35) with lactated solution (RLS) could mitigate cold IR injury in Wistar rats. METHODS: Livers were isolated, preserved for 24 h and flushed immediately before ex vivo reperfusion with either RLS or PEG35-enriched RLS. Liver injury, graft function, energy balance, autophagy, oxidative stress as well as inflammatory response were assessed. RESULTS: Flushing hepatic grafts with PEG35-enriched RLS resulted in decreased transaminase levels after cold ischemia. The improved graft function was evidenced by increased bile flow, enhanced BSP clearance, and reduced vascular resistance in these flushed grafts. Phospho-AMPK protein expression, as well as LC3B gene and protein expression were significantly increased compared to those unflushed and flushed only with RLS. PEG35-enriched RLS also maintained the oxidative state, as indicated by reduced activities of antioxidant enzymes and decreased MDA concentration. Additionally, this graft rinse solution down-regulated the inflammatory response by inhibiting the expression of genes involved in the HMGB-1/NF-κB/TNF-α signaling pathway. CONCLUSION: These data strongly suggest that rinsing liver grafts with PEG35-enriched RLS prior to reperfusion represents a simple and cost-effective strategy to enhance liver functional recovery after cold IR injury. This approach could serve as a viable alternative to RLS in clinical applications, highlighting the need for further research to explore its broader implications.