Optimal Conditions for Oxygenated Subnormothermic Machine Perfusion for Liver Grafts Using a Novel Perfusion Device

https://doi.org/10.1016/j.transproceed.2021.12.025Get rights and content

HIGHLIGHTS

  • Oxygenated subnormothermic machine perfusion is effective for donation after cardiac death (DCD) liver transplant.

  • Liver enzyme and interleukin 1 beta levels were higher in the DCD group than in the heart beating group.

  • Bile production in the heart beating group was higher at 30 minutes into perfusion.

  • DCD graft perfusion was the most efficient between 60 and 90 minutes after initiation.

  • Ischemia-reperfusion injury is a disadvantage of DCD grafts.

ABSTRACT

Background

Liver transplantation from donors after cardiac death (DCD) resolves donor shortages.

Purpose

We investigated the optimal time for subnormothermic oxygenated perfusion in DCD liver transplantation.

Methods

Ten F1 pigs (body weight: 27-32 kg) were allocated to 2 groups: the heart beating group (n = 6), from which livers were retrieved while the heart was beating, and the donation after cardiac death (DCD) group (n = 4), in which liver retrieval was performed on pigs under apnea-induced cardiac arrest for 20 minutes. In both groups, the livers were kept in cold storage for 2 hours after retrieval and perfused with a subnormothermic oxygenated Krebs-Henseleit buffer for 120 minutes. We used a novel perfusion device, which can set maximum perfusion pressures of arteries and portal vein, developed by Asahikawa Medical University and Chuo Seiko Co. Bile production, liver enzymes, and inflammatory cytokines were measured and the sinusoidal space, using tissue specimens taken from liver grafts, was measured at 30, 60, 90, and 120 minutes after the start of perfusion.

Results

Bile production peaked at 90 minutes. Significantly higher levels of liver enzymes and inflammatory cytokines were found in the DCD group (P < .05). The release of liver enzymes peaked at 60 minutes and that of inflammatory cytokines peaked at 90 minutes. The hepatic sinusoidal space was wide at 90 minutes and narrowed after 120 minutes.

Conclusions

The results suggest that subnormothermic oxygenation perfusion may maintain optimal graft condition until around 90 minutes and perfusion for more than 120 minutes may be counterproductive.

Section snippets

Material and Methods

All experiments were conducted in accordance with the Guide for the Care and Use of Laboratory Animals prepared by the National Academy of Sciences and published by the National Institute of Health [17] and the guidelines for animal experiments at Tohoku University. This study was approved by the institutional animal care committee of Tohoku University (2019MdA-045-04).

Bile Production

Bile production in the HB group (30 minutes: 17.87 ± 9.65 μL/kg; 60 minutes: 22.4 ± 28.5 μL//kg; 90 minutes: 29.76 ± 25.24 μL/kg; 120 minutes: 26.34 ± 18.74 μL/kg) was significantly higher than that in the DCD group (30 minutes: 4.91 ± 9.65 μL/kg; 60 minutes: 25.08 ± 36.03 μL//kg; 90 minutes: 33.37 ± 53.15 μL/kg; 120 minutes: 27.95 ± 34.38 μL/kg) at 30 minutes after the start of perfusion (P = .043), but no significant differences were found at other time points (Fig 3).

AST, ALT, LDH, and IL-1β Levels in the Perfusate

AST (30 minutes: 399.0 ±

Discussion

In this study, we investigated the optimal perfusion conditions for DCD grafts using a new perfusion device because the optimal perfusion conditions for organ perfusion have not yet been determined in the literature. To investigate the optimal duration of oxygenated subnormothermic perfusion, we performed 120-minute perfusions and examined the condition of the organ and release of waste products into the reflux fluid during the perfusion. The results showed that the release of liver enzymes

Conclusion

In this study, we investigated the optimal time for MP of DCD grafts using a novel perfusion device. In the future, accumulation of more cases is necessary to confirm the safety of this new perfusion device and expand the indications for DCD liver transplantation.

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