Hypothermic oxygenated machine perfusion in porcine donation after circulatory determination of death liver transplant.

BACKGROUND: Livers from donation after circulatory determination-of-death (DCD) donors suffer ischemic injury during a preextraction period of cardiac arrest and are infrequently used for transplantation; they have the potential, however, to considerably expand the donor pool. We aimed to determine whether hypothermic oxygenated machine perfusion would improve or further deteriorate the quality of these livers using a clinically relevant porcine model. METHODS: Donor livers were subjected to 90 min of cardiac arrest and preserved at 4°C with either static cold storage using University of Wisconsin solution (CS, n=6) or oxygenated machine perfusion using University of Wisconsin machine perfusion solution and 25% physiological perfusion pressures (HMP, n=5). After 4 hr of preservation, livers were transplanted into recipient pigs, which were followed intensively for up to 5 days. RESULTS: Five-day survival was 0 in CS and 20% in HMP. Immediately after reperfusion, hepatocellular injury and function were improved in HMP versus CS. However, HMP grafts also demonstrated significant endothelial and Kupffer cell injury, and a progressive lesion developed 24 to 48 hr after reperfusion that led to death in all but one of the recipient animals. CONCLUSIONS: Although hypothermic oxygenated machine perfusion performed using subphysiological perfusion pressures seems to offer some advantages over cold storage in the preservation of ischemically damaged livers, it simultaneously conditions endothelial and Kupffer cell injury that may ultimately lead to the failure of these grafts

Superior preservation of DCD livers with continuous normothermic perfusion.

OBJECTIVE: Unexpected donation after cardiac death (DCD) donors suffer cardiac arrest suddenly and are maintained with normothermic extracorporeal membrane oxygenation (NECMO) while consent for donation is obtained. The objective of this study was to determine whether ex vivo normothermic machine perfusion (NMP) improves upon the benefits of NECMO in a large-animal model of unexpected DCD liver transplant. METHODS: Donor pigs underwent 90-minute cardiac arrest and were divided in to 3 groups. In the first, livers were preserved immediately with cold storage (CS, n = 6). In the other 2 groups, donors underwent 60-minute NECMO followed by CS (NECMO+CS, n = 6) or NMP (NECMO+NMP, n = 6). After 4-hour preservation, livers were transplanted into recipient pigs. RESULTS: Five-day survival was 0 in CS, 83% in NECMO+CS, and 100% in NECMO+NMP. After reperfusion, injury, and inflammatory markers rose significantly among CS grafts, all of which developed primary nonfunction. Sixty minutes of NECMO, however, resulted in only 1 death, whereas NECMO followed by NMP led to no deaths and significant improvements in injury, inflammation, and synthetic function in comparison to NECMO and CS. CONCLUSION: Although 60 minutes recuperative NECMO is better than CS alone, NMP improves further on NECMO and may have a role in preserving DCD livers in the clinical setting

A systematic review and meta-analyses of regional perfusion in donation after circulatory death solid organ transplantation

In donation after circulatory death (DCD), (thoraco)abdominal regional perfusion (RP) restores circulation to a region of the body following death declaration. We systematically reviewed outcomes of solid organ transplantation after RP by searching PubMed, Embase, and Cochrane libraries. Eighty-eight articles reporting on outcomes of liver, kidney, pancreas, heart, and lung transplants or donor/organ utilization were identified. Meta-analyses were conducted when possible. Methodological quality was assessed using National Institutes of Health (NIH)-scoring tools. Case reports (13/88), case series (44/88), retrospective cohort studies (35/88), retrospective matched cohort studies (5/88), and case-control studies (2/88) were identified, with overall fair quality. As blood viscosity and rheology change below 20 °C, studies were grouped as hypothermic (HRP, ≤20 °C) or normothermic (NRP, >20 °C) regional perfusion. Data demonstrate that RP is a safe alternative to in situ cold preservation (ISP) in uncontrolled and controlled DCDs. The scarce HRP data are from before 2005. NRP appears to reduce post-transplant complications, especially biliary complications in controlled DCD livers, compared with ISP. Comparisons for kidney and pancreas with ISP are needed but there is no evidence that NRP is detrimental. Additional data on NRP in thoracic organs are needed. Whether RP increases donor or organ utilization needs further research