Elsevier

Surgery

Volume 158, Issue 6, December 2015, Pages 1642-1650
Surgery

Transplantation
Normothermic extracorporeal liver perfusion for donation after cardiac death (DCD) livers

https://doi.org/10.1016/j.surg.2015.07.016Get rights and content

Background

The susceptibility of extended criteria livers to ischemia reperfusion injury is a major obstacle in organ cold preservation. Normothermic extracorporeal liver perfusion (NELP) has been investigated to reduce ischemic damage, restore physiologic function, and assess viability of the liver prior to transplant. The goal of this study is to compare physiological parameters of livers maintained continuously on NELP to those preserved in cold solution.

Methods

Livers from 9 female landrace pigs were subjected to either 20 minutes (W20-NELP), 40 minutes (W40-NELP), or 60 minutes (W60-NELP) of warm ischemia followed by 6 hours of NELP followed by a 2-hour NELP evaluation phase. This was compared with 3 livers subjected to 40 minutes of warm ischemia time followed by 6 hours of cold storage (W40-Cold) and a 2-hour NELP evaluation phase. Groups were compared with the 2-way analysis of variance test.

Results

NELP stabilized transaminases accompanied by significant improvement in bile production and decline in lactate and INR values in all W-NELP groups. Histologic analysis demonstrated significant improvement from 0 hour (mild-to-moderate sinusoidal dilation and zone 3 necrosis) to the end of the NELP run (minimal necrosis and mild IRI). Comparison of W40-NELP and W40-Cold revealed greater bile production and oxygen extraction ratio in W40-NELP. In contrast, markers of cellular and functional damage were increased in the W40-Cold group.

Conclusion

NELP improves metabolic and functional parameters of livers with either short or extended warm ischemia times compared with livers subjected to comparable cold ischemia times.

Section snippets

Animals

Twelve female land race/farm pigs (30–34 kg) were purchased from Oak Hill Genetics, IL. All animals were housed and maintained in accordance with the National Resource Council guidelines. All experimental procedures and protocols were approved by the Animal Studies committee and Department of Comparative Medicine at the Washington University School of Medicine in St Louis. They were given access to food and water ad libitum and were restricted from solid food but not water 12 hours before the

NELP reduces hepatocyte injury of DCD livers compared with grafts preserved in cold storage

To evaluate the efficacy of NELP in recovering DCD livers, livers were subjected to warm ischemia and then either placed on NELP or maintained in cold storage for 6 hours. Livers from both groups were then placed onto NELP for a final 2-hour period to simulate posttransplant conditions in which measurements of the liver physiologic function were collected. We measured liver enzymes as markers of liver injury and necrosis.

In the first set of experiments, we evaluated graft function, degree of

Discussion

In this study, we for the first time compared outcomes of warm perfusion and cold preservation of the liver during a functional reperfusion period. We demonstrate that normothermic perfusion has the potential to recover and stabilize warm ischemic injured livers by providing full metabolic support and oxygenation to the liver tissue by re-establishing physiologic flows and parameters. Prior studies have shown the feasibility of NELP by comparing standard cold storage to NELP after warm

References (23)

  • P.A. Clavien et al.

    Preservation and reperfusion injuries in liver allografts. An overview and synthesis of current studies

    Transplantation

    (1992)
  • Cited by (0)

    This project was funded by the Barnes Jewish Hospital Foundation Project Award, Transplant Research Support.

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