**5.2 Inflammation limiting strategies to preserve procured organs**

After procurement, organs are further exposed to injury due to removal from their physiological conditions. Hypoxic injury has a detrimental effect on organ structure and function, and adds to increased immunogenicity. Prolonged ischemia, cold or warm, is a risk factor for early graft dysfunction and worse long-term outcomes. The duration and type (warm or cold) of ischemia time may also directly influence cytokine production [19]. Significant cytokine gene expression has otherwise already occurred directly after brain death. Namely, the cytokine gene expression before transplantation was shown to be even higher than during the period of acute rejection [35]. A strong association was recently identified between cold ischemia time and the levels of IL-1 and IL-8 in human liver transplants. Warm ischemia time also correlated with IL-6 and IL-10 in the same study [54].

Successful preservation strategies are key to minimize ischemic damage and the effect of reperfusion with associated increased immunogenicity after organ implantation. The current accepted standard for most solid organs is static cold storage (SCS), where the solid organ is stored on ice after removal from the donor, and then removed from the ice box at the time of implantation. However, novel technologies enable perfusion of the donated organ during the transport phase or at the recipient centre, with the option to use a variety of temperatures and different perfusates. Machine perfusion systems (hypothermic, normothermic, oxygen persufflation) represent dynamic preservational methods.

Hypothermic preservation strategies are now widely used to decrease inflammation, depress the metabolic rate of cells, and reduce the effects of ischemia [55, 56]. In the largest meta-analysis performed so far [57], hypothermic machine perfusion (HMP) was superior to SCS in deceased donor kidney transplantation (this was true for both DBD and DCD kidneys). The incidence of delayed graft function in kidneys from deceased brain donors was much lower in the group with hypothermic perfusion. Additionally, reports of economic analysis suggested that HMP can lead to cost savings in both North American and European settings.

Since very low temperatures can also have harmful repercussions on organs in terms of cytokine and reactive oxygen production [58], over the last two decades several research groups have examined the effects of increasing the temperature of machine perfusion to near-normothermic temperatures (20–33°C). Nearnormothermic preservation is particularly applicable for organs of marginal donors or donors after cardiac death. In these cases, due to prolonged warm ischemia times, organ viability is negatively impacted by the subsequent cold preservation. Hence, normothermic perfusion may enhance preservation and transplantation outcomes and reduce the risk of non-functional organs [59].
