For extended criteria donor organs or DCDD organs, what unique benefit does machine perfusion offer beyond simple preservation?

Extended criteria donor (ECD) organs are those from donors with characteristics that typically pose a higher risk of poorer outcomes post-transplantation, such as advanced age or comorbidities. Donation after circulatory death (DCDD) organs are retrieved after the donor's heart has stopped beating, resulting in a period of warm ischemia, where the organ is deprived of blood flow at body temperature before preservation begins. Simple preservation, known as static cold storage, involves immersing the organ in a cold solution, slowing its metabolism to minimize damage. However, for ECD and DCDD organs, which often arrive with pre-existing damage or have experienced warm ischemia, static cold storage offers no opportunity to assess their actual functional health or to actively improve their condition.

Machine perfusion, in contrast, circulates a specialized preservation solution through the organ's vasculature at controlled temperatures, either hypothermic (cold) or normothermic (body temperature). Beyond mere preservation, machine perfusion offers two unique and critical benefits for ECD and DCDD organs. First, it provides an active platform for viability assessment and real-time evaluation of organ function prior to transplantation. During perfusion, parameters such as vascular resistance, perfusate flow rate, and the leakage of cellular enzymes or clearance of metabolic waste products like lactate can be continuously monitored. For example, a liver organ might be assessed for its bile production or a kidney for its perfusate lactate clearance. This allows transplant teams to objectively determine if a marginal ECD or DCDD organ, which might otherwise be discarded due to donor characteristics or warm ischemic insult, is functionally viable enough for successful transplantation, thereby increasing the usable organ pool and reducing the risk of primary non-function or delayed graft function in the recipient.

Second, machine perfusion enables active reconditioning, repair, and therapeutic intervention during the preservation period. The continuous flow helps to wash out accumulated toxic metabolites that build up during ischemia and are not removed by static storage. In normothermic machine perfusion, the perfusate can be oxygenated and contain nutrients, allowing the organ to resume some metabolic activity and produce energy, actively repairing cellular damage sustained during the donor period, especially critical for DCDD organs that have experienced warm ischemia. Furthermore, therapeutic agents such as anti-inflammatory drugs, antioxidants, or vasodilators can be added to the perfusate to directly treat the organ, mitigating further injury and improving its function. This active environment reduces the impact of ischemia-reperfusion injury, which is the damage that occurs when blood flow is restored to an ischemic organ in the recipient, a major concern for ECD and DCDD organs. By providing a controlled reintroduction of oxygen and nutrients and enabling active repair, machine perfusion actively improves the quality and resilience of these challenging organs, making them safer and more effective for transplantation.