Perla®: redefining organ preservation for early graft protection

The increasing use of extended-criteria donors (ECD) and donation-after-circulatory-death (DCD) grafts has reinforced the need for preservation strategies capable of addressing their greater vulnerability to ischemia–reperfusion injury (IRI). Despite major advances in machine perfusion, abdominal grafts are routinely first exposed to a preservation solution during donor washout and cooling. This early intervention therefore represents a unique opportunity to initiate graft protection. This Perspective discusses the evolution of organ preservation from the maintenance of an appropriate physicochemical environment toward a strategy combining preservation with targeted biochemical protection against IRI. Within this framework, Perla® illustrates this approach by combining an extracellular, sodium-rich physicochemical environment, polyethylene glycol (PEG) as an oncotic agent, impermeant and buffering capacity with three repurposed medicinal agents: trimetazidine, carvedilol, and tacrolimus, selected to provide complementary support against interconnected metabolic, mitochondrial, oxidative, calcium-dependent, microvascular, and inflammatory processes involved in IRI. Preclinical findings provide a supportive biological and mechanistic evidence for this preservation concept. The transition from experimental evaluation to clinical implementation offers an opportunity to determine whether optimizing the preservation solution from the initial flushing and cooling stages can contribute to early graft recovery and post transplant outcomes in contemporary transplantation pathways. This Perspective therefore highlights the need to reassess preservation-solution composition alongside evolving preservation modalities and donor profiles. Organ preservation should therefore be viewed not merely as a means of maintaining graft viability during ischemia, but as an early opportunity to prepare and protect the graft for reperfusion and transplantation.