Organ preservation and machine perfusion

Organ preservation is the set of techniques used to keep a recovered organ viable during the interval between its removal from a donor and its implantation into a recipient. The two broad approaches are static cold storage (SCS), in which the flushed organ is held cold and motionless on ice, and machine perfusion, in which a device continuously circulates a fluid through the organ's vasculature. Preservation methods aim to slow metabolism, limit ischemic injury, and, in some machine-perfusion modes, to assess, monitor, or recondition the organ before transplantation.[1][2]

The choice of method depends on the organ, the donor type, and the anticipated preservation time. Static cold storage remains simple, inexpensive, and the default for many standard-risk organs, while machine perfusion has expanded rapidly since the 2010s for higher-risk grafts, longer preservation, and organs recovered after circulatory death.[1][2][3] This article concerns ex situ preservation of an organ that has already been recovered; for the in-situ technique applied to the donor's body before recovery, see Normothermic regional perfusion.

The preservation problem

Once an organ's blood supply is interrupted, it sustains ischemic injury from oxygen and nutrient deprivation. Two phases are distinguished: warm ischemia, at or near body temperature (for example, during the agonal phase of donation after circulatory death or at the moments of recovery and implantation), and cold ischemia, the deliberately cooled storage interval. Cooling to roughly 4 °C slows cellular metabolism several-fold, buying time, but it does not stop injury.[1][2] When perfusion is restored in the recipient, a further insult, ischemia-reperfusion injury, occurs as reoxygenation drives reactive-oxygen-species formation, mitochondrial dysfunction, and inflammation.[1][2]

Each organ tolerates cold ischemia for only a limited time before the risk of delayed graft function, primary nonfunction, or biliary and vascular complications rises. Commonly cited working limits for static cold storage are approximately 4-6 hours for heart and lung, 8-12 hours for liver, 12-18 hours for pancreas, and up to 24-36 hours for kidney, though these vary with donor quality and are not absolute thresholds.[4][5]

Static cold storage

In static cold storage the recovered organ is flushed with a cold preservation solution to clear blood and deliver protective agents, then bagged and packed in sterile ice for transport.[1][2] The method's advantages are simplicity, low cost, portability, and decades of clinical experience; its limitation is that it only slows, rather than supports, metabolism and offers no way to assess organ function during storage.[1][2][3] Static cold storage remains the most widely used preservation method worldwide.[2]

Preservation solutions

Cold-storage solutions are formulated to counter the consequences of hypothermic, ischemic storage: cell swelling, acidosis, oxidative injury, and depletion of energy substrates. They are broadly classified as intracellular-type (low sodium, high potassium, mimicking the intracellular milieu) or extracellular-type (higher sodium, lower potassium).[2][6]

| Solution | Type | Notes | |---|---|---| | University of Wisconsin (UW; "Belzer," ViaSpan, SPS-1) | Intracellular | Developed in the late 1980s by Folkert Belzer and James Southard; uses lactobionate and raffinose as impermeants, hydroxyethyl starch as colloid, plus glutathione, allopurinol, and adenosine. Long the standard for abdominal organs.[6][7] | | HTK (histidine-tryptophan-ketoglutarate; Custodiol) | Intermediate/extracellular | Low-viscosity, histidine-buffered; widely used for abdominal and thoracic organs.[2][6] | | Celsior | Extracellular | Originally developed for the heart; also used for liver and other organs.[2][6] |

The University of Wisconsin solution, introduced for pancreas preservation and soon adopted for liver and kidney, displaced the earlier EuroCollins solution and permitted longer, safer cold storage; its impermeant anions limit cell swelling, while glutathione and allopurinol act as antioxidants and adenosine supports energy regeneration.[6][7]

Machine perfusion overview

Machine perfusion connects the recovered organ to a circuit that continuously pumps a preservation or perfusate fluid through its vasculature. Compared with static storage, perfusion can deliver oxygen and metabolic substrates, wash out waste, and, at higher temperatures, restore enough metabolism to let clinicians measure how the organ functions before committing it to a recipient.[1][2][3] Perfusion modes are distinguished mainly by temperature: hypothermic (~4-10 °C), subnormothermic (~20-25 °C), and normothermic (~35-37 °C), with or without active oxygenation.[1][2]

Hypothermic machine perfusion (HMP) and HOPE

In hypothermic machine perfusion the organ is perfused cold, keeping metabolism low while improving on the homogeneity of a static flush. For kidneys, a large international randomized trial (Moers et al., 2009) found that hypothermic machine perfusion reduced delayed graft function and improved one-year graft survival compared with static cold storage in deceased-donor kidneys.[8]

Adding oxygen to cold perfusion, hypothermic oxygenated perfusion (HOPE), or dual HOPE (D-HOPE) when both portal vein and hepatic artery are perfused, has been studied especially for the liver. A multicenter randomized trial in livers from donation after circulatory death (van Rijn et al., 2021) reported that end-ischemic dual hypothermic oxygenated perfusion lowered the incidence of non-anastomotic biliary strictures and early allograft dysfunction relative to static cold storage.[9] The proposed mechanism is reduction of mitochondrial reactive-oxygen-species release at reperfusion.[9]

Normothermic machine perfusion (NMP)

Normothermic machine perfusion maintains the organ near body temperature with oxygenated, often blood-based, perfusate, recreating near-physiologic conditions. Because the organ is metabolically active, NMP allows viability assessment and a degree of resuscitation of marginal grafts in addition to preservation.[1][2][3]

• Liver. Ex situ normothermic machine perfusion of the liver (delivered by devices such as portable normothermic perfusion systems) was tested against static cold storage in a multicenter randomized trial (Nasralla et al., 2018), which found reduced peak post-transplant aspartate-aminotransferase levels, less early allograft dysfunction, lower organ-discard rates, and longer feasible preservation, although graft and patient survival did not differ.[10] Normothermic perfusion also enables transplantation of selected livers that would otherwise be declined, by demonstrating adequate function during perfusion.[3][10]
• Lung. Ex vivo lung perfusion (EVLP) perfuses and ventilates recovered lungs at normothermia to assess and potentially recondition high-risk donor lungs. An early clinical study (Cypel et al., 2011) showed that lungs initially considered marginal could be evaluated on EVLP and transplanted with primary graft dysfunction rates comparable to conventionally selected lungs.[11]
• Heart. Normothermic ex situ perfusion has enabled clinical transplantation of hearts from donation after circulatory death by reperfusing and assessing the heart after recovery; registry analyses of DCD heart transplantation report short-term survival comparable to donation after brain death, though with signals such as higher early acute rejection.[12]

Evidence and adoption

Randomized and registry evidence supports machine perfusion most strongly for reducing delayed graft function in kidneys (HMP) and for reducing ischemic biliary complications and discard in livers (HOPE and NMP), with the additional, distinctive benefit of in-perfusion viability testing for liver, lung, and heart.[8][9][10][11][12] Adoption accelerated after regulatory clearances in the United States and Europe for several liver, kidney, lung, and heart perfusion systems, and uptake has been especially pronounced in DCD transplantation, where perfusion both extends logistics and rehabilitates grafts exposed to warm ischemia.[3][12] The device landscape includes hypothermic and normothermic systems from several manufacturers; this article does not endorse any specific product, and clinical practice continues to evolve as further trial data accrue (as of 2026).[2][3]

Normothermic regional perfusion contrast

Machine perfusion as described above is ex situ: the organ is perfused after it has been removed from the body. A related but distinct technique, normothermic regional perfusion (NRP), is performed in situ, circulation is restored regionally within the deceased donor's body (using extracorporeal circuit techniques) after circulatory-death declaration and before the organs are recovered. NRP is used chiefly in controlled DCD to restore organ perfusion and assess function in place, and it is ethically contested; it is treated separately in Normothermic regional perfusion.[1][12]

See also

• Organ procurement and recovery surgery
• Normothermic regional perfusion (NRP)
• Donation after circulatory death (DCD)
• Donation after brain death (DBD)
• The donation pathway

References

• Jing L, Yao L, Zhao M, et al. Organ preservation: from the past to the future. Acta Pharmacol Sin. 2018;39(5):845-857. doi:10.1038/aps.2017.182. PMID:29565040. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5943906/
• Petrenko A, Carnevale M, Somov A, et al. Organ preservation into the 2020s: the era of dynamic intervention. Transfus Med Hemother. 2019;46(3):151-172. doi:10.1159/000499610. PMID:31244584. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6558325/
• Cleveland Clinic. Machine perfusion: a new era in organ transplantation (overview of hypothermic and normothermic dynamic preservation). https://consultqd.clevelandclinic.org/machine-perfusion-dynamic-preservation-represents-new-era-in-transplantation
• Vagefi PA, et al. Organ Preservation: Practice Essentials and Pathophysiology. Medscape Reference. https://emedicine.medscape.com/article/431140-overview
• Stahl JE, et al. Cold ischemia time and graft outcome (overview of organ-specific limits). Cold ischemia time in liver transplantation: an overview. World J Transplant / PMC. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11212655/
• Latchana N, Peck JR, Whitson BA, Black SM. Preservation solutions for cardiac and pulmonary donor grafts / Organ preservation solutions in transplantation. Exp Clin Transplant. 2021;19(6):511-. https://www.ectrx.org/detail/current/2021/19/6/0/511/0 (UW composition and intracellular/extracellular classification).
• Ploeg RJ, Goossens D, McAnulty JF, Southard JH, Belzer FO. Successful 72-hour cold storage of dog kidneys with UW solution; Belzer FO, Southard JH. Principles of solid-organ preservation by cold storage. Transplantation. 1988;45(4):673-676. PMID:3282347. https://pubmed.ncbi.nlm.nih.gov/3282347/
• Moers C, Smits JM, Maathuis MH, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009;360(1):7-19. doi:10.1056/NEJMoa0802289. PMID:19118301. https://www.nejm.org/doi/full/10.1056/NEJMoa0802289
• van Rijn R, Schurink IJ, de Vries Y, et al. Hypothermic machine perfusion in liver transplantation, a randomized trial (DHOPE-DCD). N Engl J Med. 2021;384(15):1391-1401. doi:10.1056/NEJMoa2031532. PMID:33626248. https://www.nejm.org/doi/full/10.1056/NEJMoa2031532
• Nasralla D, Coussios CC, Mergental H, et al. A randomized trial of normothermic preservation in liver transplantation. Nature. 2018;557(7703):50-56. doi:10.1038/s41586-018-0047-9. PMID:29670285. https://www.nature.com/articles/s41586-018-0047-9
• Cypel M, Yeung JC, Liu M, et al. Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med. 2011;364(15):1431-1440. doi:10.1056/NEJMoa1014597. PMID:21488765. https://www.nejm.org/doi/full/10.1056/NEJMoa1014597
• Schroder JN, et al.; and Kwon JH, et al. DCD heart transplantation: normothermic regional perfusion versus direct procurement and machine perfusion, outcomes. JACC Heart Fail. 2024;12(8). doi:10.1016/j.jchf.2024.06.007. PMID:39093259. https://www.jacc.org/doi/10.1016/j.jchf.2024.06.007