Dataset Information

Oxygenated versus non-oxygenated flush out and storage of donor livers: An experimental study.

ABSTRACT:

Background

During donor organ procurement and subsequent static cold storage (SCS), hepatic adenosine triphosphate (ATP) levels are progressively depleted, which contributes to ischemia-reperfusion injury (IRI). We sought to investigate a simple approach to prevent ATP depletion and IRI using a porcine donation after circulatory death (DCD) liver reperfusion model.

Methods

After 30 min warm ischemia, porcine livers were flushed via the portal vein with cold (4°C) non-oxygenated University of Wisconsin (UW) preservation solution (n = 6, control group) or with oxygenated UW (n = 6, OxyFlush group). Livers were then subjected to 4 h SCS in non-oxygenated (control) or oxygenated (OxyFlush) UW, followed by 4 h normothermic reperfusion using whole blood. Hepatic ATP levels were compared, and hepatobiliary function and injury were assessed.

Results

At the end of SCS, ATP was higher in the OxyFlush group compared to controls (delta ATP of +0.26 vs. -0.68 µmol/g protein, p = 0.04). All livers produced bile and metabolized lactate, and there were no differences between the groups. Grafts in the OxyFlush group had lower blood glucose levels after reperfusion (p = 0.04). Biliary pH, glucose and bicarbonate were not different between the groups. Injury markers including liver transaminases, lactate dehydrogenase, malondialdehyde, cell-free DNA and flavin mononucleotide in the SCS solution and during reperfusion were also similar. Histological assessment of the parenchyma and bile ducts did not reveal differences between the groups.

Conclusion

Oxygenated flush out and storage of DCD porcine livers prevents ATP depletion during ischemia, but this does not seem sufficient to mitigate early signs of IRI.

SUBMITTER: Bruggenwirth IMA

PROVIDER: S-EPMC9299999 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:INTRODUCTION:Extended criteria donor (ECD) livers are increasingly accepted for transplantation in an attempt to reduce the gap between the number of patients on the waiting list and the available number of donor livers. ECD livers; however, carry an increased risk of developing primary non-function (PNF), early allograft dysfunction (EAD) or post-transplant cholangiopathy. Ischaemia-reperfusion injury (IRI) plays an important role in the development of these complications. Machine perfusion reduces IRI and allows for reconditioning and subsequent evaluation of liver grafts. Single or dual hypothermic oxygenated machine perfusion (DHOPE) (4°C-12°C) decreases IRI by resuscitation of mitochondria. Controlled oxygenated rewarming (COR) may further reduce IRI by preventing sudden temperature shifts. Subsequent normothermic machine perfusion (NMP) (37°C) allows for ex situ viability assessment to facilitate the selection of ECD livers with a low risk of PNF, EAD or post-transplant cholangiopathy. METHODS AND ANALYSIS:This prospective, single-arm study is designed to resuscitate and evaluate initially nationwide declined ECD livers. End-ischaemic DHOPE will be performed for the initial mitochondrial and graft resuscitation, followed by COR of the donor liver to a normothermic temperature. Subsequently, NMP will be continued to assess viability of the liver. Transplantation into eligible recipients will proceed if all predetermined viability criteria are met within the first 150?min of NMP. To facilitate machine perfusion at different temperatures, a perfusion solution containing a haemoglobin-based oxygen carrier will be used. With this protocol, we aim to transplant extra livers. The primary endpoint is graft survival at 3 months after transplantation. ETHICS AND DISSEMINATION:This protocol was approved by the medical ethical committee of Groningen, METc2016.281 in August 2016 and registered in the Dutch Trial registration number TRIAL REGISTRATION NUMBER: NTR5972, NCT02584283.