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Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death

  • Original Article
  • Artificial Liver, Pancreas
  • Published:
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Abstract

Improvement of machine perfusion (MP) technologies is required to enhance organ quality for donor after cardiac death (DCD) grafts. Installing a dialyzer or a filter into the perfusion circuit to maintain the perfusate condition has some advantages. However, the consequences of purification perfusate during subnormothermic machine perfusion (SNMP) remain unexplained. In this study, the effects of initial purification perfusate with simple method of replacing the first 0.5-L perfusate during SNMP were investigated to consider installation effect of the filter or the dialyzer. Porcine liver grafts, which have 60-min warm ischemia time, were procured to imitate the DCD graft condition. Purified SNMP (PSNMP) results were compared with simple cold storage and conventional SNMP. In PSNMP, initial perfusate of 0.5 L was removed to substitute for purification. After preservation process, the preserved grafts were reperfused with diluted autologous blood for 2 h under normothermic machine perfusion condition to evaluate the liver function using an isolated reperfusion model. The vascular pressures, enzyme release rates and the metabolic indexes during reperfusion were analyzed. The pressures in the hepatic artery after reperfusion 60 min were significantly lower in PSNMP group compared with cold storage (CS) and SNMP groups. In addition, lactate dehydrogenase and alkaline phosphatase were significantly lower after PSNMP than after the CS or SNMP. Also, the metabolic indexes of hyaluronic acid and lactate were significantly decreased by purifying the perfusate in MP preservation than in CS or SNMP. The effectiveness of initial purification perfusate during SNMP was investigated.

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Abbreviations

AST:

Aspartate aminotransferase

ALP:

Alkaline phosphatase

CS:

Simple cold storage

DCD:

Donated after cardiac death

ECD:

Extended criteria donors

HA:

Hepatic artery

IRM:

Isolated reperfusion model

LDH:

Lactate dehydrogenase

NMP:

Normothermic machine perfusion

MP:

Machine perfusion

PV:

Portal vein

SNMP:

Subnomothermic machine perfusion

WIT:

Warm ischemia time

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Acknowledgements

We thank all of the lab members and colleagues for their helpful suggestions and assistance in the experiments. This works was supported by JSPS KAKENHI(15H03922 to H.O and M.N) from the Japan Society for the Promotion of Science (JSPS), the Ring Ring project (26-105 to H.O)of the JKA Foundation and a Grant-in-Aid for Innovative Research in Life Science from Asahikawa Medical University.

Funding

This work was supported by the Ring Ring Project (26-105 to H.O) of the JKA Foundation, JSPS KAKENHI (#15H03922 to H.O and N. Matsuno) from the Japan Society for the Promotion of Science (JSPS), and a Grant-in-Aid for Innovative Research in Life Science from Asahikawa Medical University to N. Matsuno.

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Authors and Affiliations

  1. Department of Mechanical Engineering, Tokyo Metropolitan University, 1-1 Minam Osawa, Hachioji, Tokyo, 192-0397, Japan

    Hiromichi Obara, Noriyuki Morito, Naoto Matsuno & Ryo Yoshikawa

  2. Department of Surgery, Asahikawa Medical University, 2-1-1-1 Midorigaoka higashi, Asahikawa, Hokkaido, 078-8510, Japan

    Hiromichi Obara, Naoto Matsuno, Mikako Gochi, Masahide Otani, Tatsuya Shonaka & Hiroyuki Furukawa

  3. National Center for Child Health and Development, 2-10-1 Okura, Setagaya, Tokyo, 157-8535, Japan

    Hiromichi Obara, Naoto Matsuno & Shin Enosawa

  4. Veterinary Teaching Hospital, Azabu University, 1-17-71 Fuchinobe, Chuo, Sagamihara, Kanagawa, 252-5201, Japan

    Tetsuya Nakajo

  5. Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Toshihiko Hirano

Authors
  1. Hiromichi Obara
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Contributions

NM, NM and HO designed research. HO, NM, NM, RY, TN performed the experiment. TH prepared the paerfusate. RY, NM analyzed the data. SE helped discussions. NM and HO drafted the manuscript. HF and HO supervised the drafting of the manuscript. SE helped discuss the findings.

Corresponding author

Correspondence to Hiromichi Obara.

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The authors declare no conflicts of interest in association with the present study.

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Obara, H., Morito, N., Matsuno, N. et al. Initial perfusate purification during subnormothermic machine perfusion for porcine liver donated after cardiac death. J Artif Organs 23, 62–69 (2020). https://doi.org/10.1007/s10047-019-01123-5

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