Organ preservation. Which temperature for which organ?

In 1954, Joseph Murray performed the first successful human organ transplant from a live kidney donor, Richard Herrick, into the donor’s twin, Robert. Since no form of organ preservation was available, the surgeries happen in two simultaneous operating rooms. In this way, the kidney damage subsequent to the lack of blood supply before the vascular anastomoses between Richard’s vessels and Robert’s kidney were confectioned, was reduced to the shortest possible (1). Richard recovered well and died in 1962 for recurrence of his original nephritis disease. Seventy years later from Murray’s pioneering surgery, the optimal graft preservation prior to implantation in the recipient’s body remains one of the major challenges in transplantation. The primary graft function and its long-term outcomes are dependant from the ischaemia-reperfusion injury (IRI)(2), with considerable parenchymal damage occurring after retrieval and before implant, during the preservation period. There is evidence that different organs have different resistance thresholds to the ischaemic insult, and these thresholds could be affected by the preservation modality (3, 4). The three main organ preservation techniques include static cold storage (SCS), Hypothermic Machine Perfusion (HMP) and Normothermic Machine Perfusion (NMP); to date, SCS is still the most common preservation modality because of its simplicity and lower cost, despite growing evidence of a higher risk of subsequent transplant failure (5). Literature has shown that organs retrieved from extend criteria donors (ECD) and donors after cardiocirculatory death (DCD), are more susceptible to the IRI when compared to standard donors (6, 7). Thus, to keep expanding the donor pool with marginal organs, it is paramount to tailor the preservation modality to the characteristics of the single isolated graft (8). Ex situ organ perfusion was introduced in the early 1900s by Charles Lindbergh and Alexis Carrel, who developed the first idea of HMP to preserve kidneys and vessels (9), but it was not until 1967, when Belzer transplanted a deceased donor kidney after 17 hours of preservation, including HMP (10). The graft worked immediately post transplantation. What is the rationale to cool the organ down before implantation? Is there a temperature paradigm? We know that in kidneys, hypothermia slows down the cell metabolism, thus reducing oxygen requirements during the ischaemic period outside the human body (11). Yet, there is no evidence on the gold standard temperature for the rest of the human grafts. Unpublished data from our laboratory, assessed the role of different temperature in terms of human cell survival after the ischaemic insult: we found that the optimal temperature storage is the same for kidney and heart (4 C°), but higher for lung (7C°) and lower for the liver (1C°). Despite these findings are limited to in vitro models, in 1998, we copyrighted a device allowing modification of the temperature according to the human graft to transport (12). This was a compact bio air conditioner able to switch and maintain a set temperature between -20 C° and + 37C°, to allow storage of different organs and tissues from the donor’s hospital to the recipient’s site. Is 37 C°, the human body temperature, a possible way forward? The NRP basic principle of organ preservation is to minimize the deleterious effects of ischemia and anoxia while the organ is outside the human body. The hypothermic setting slows the cell metabolism and demand for oxygen, but it does not prevent the chemical processes that cause the ischemic injury during the preservation period. Despite the possibility to deliver oxygen during HMP, in what is so called the Hypothermic Oxygenated Machine Perfusion (HOPE), in preliminary studies, NRP seems to provide in addition of oxygen, a platform to repair marginal organs by delivering therapeutics (13). In conclusion, one size might not fit all. It is still not clear which temperature setting is to prefer to another for an optimal organ preservation. Current research is directed at different techniques to improve practices, assessment and reconditioning of organ viability pre-transplantation.