Protective strategies and therapeutic interventions for ischemia-reperfusion injury: potential applications in normothermic machine perfusion.

Recent advances in perfusion technology have positioned normothermic machine perfusion (NMP) as a promising alternative. However, the unavoidable occurrence of ischemia-reperfusion injury (IRI) during perfusion remains a critical barrier to enhancing postoperative outcomes and graft survival. This review systematically examines current pharmacological strategies to mitigate IRI in NMP, targeting key pathological mechanisms including oxidative stress, inflammatory cascades, apoptotic pathways, and endothelial dysfunction. We highlight promising therapeutic agents that have demonstrated efficacy in animal models, preclinical experiments, and ex vivo human liver studies. In addition, we discuss the current challenges in clinical translation and future development directions.