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The Effects of Short-term Subnormothermic Perfusion After Cold Preservation on Liver Grafts From Donors After Circulatory Death: An Ex Vivo Rat Model

Kakizaki, Yuta, MD1; Miyagi, Shigehito, MD, PhD1; Shimizu, Kenji, MD, PhD1; Miyazawa, Koji, MD, PhD1; Nakanishi, Wataru, MD, PhD1; Tokodai, Kazuaki, MD, PhD1; Hara, Yasuyuki, MD, PhD1; Nakanishi, Chikashi, MD, PhD1; Unno, Michiaki, MD, PhD1; Kamei, Takashi, MD, PhD1; Goto, Masafumi, MD, PhD2; Satomi, Susumu, MD, PhD1

doi: 10.1097/TP.0000000000002080
Original Basic Science—Liver

Background We previously reported that short oxygenated warm perfusion before cold storage (CS) had improved the graft viability of rat livers from donors after circulatory death (DCD). In this study, we investigated the effectiveness of short-term oxygenated subnormothermic perfusion for different durations after CS in a rat DCD model.

Methods We used an isolated perfused rat liver system. In study 1: the grafts were retrieved from Wistar rats 30 minutes after cardiac arrest (thoracotomy), preserved in CS for 6 hours, and perfused with oxygenated subnormothermic (20-25°C) Krebs-Henseleit buffer for different durations (0, 15, 30, 60, and 90 minutes groups; n = 5 in each). In study 2: in addition to subnormothermic ex vivo liver perfusion (SELP), after 15-minute incubation at room temperature, the grafts were reperfused under normothermic condition for 60 minutes as a model of liver transplantation (0, 30, 60, and 90 minutes groups; n = 5 in each).

Results In study 1, portal flow, bile production and tissue adenosine triphosphate increased with perfusion duration. In study 2, SELP significantly improved portal flow volume (P <0.05), and bile production (P <0.05), decreased liver enzymes (P <0.05) and cytokines (P <0.0001), and increased tissue adenosine triphosphate (P <0.01). Histological examinations showed that additional SELP ameliorated tissue deterioration, preserved the parenchymal structure, and decreased apoptosis (P <0.01). Furthermore, scanning electron microscopy revealed that additional SELP alleviated sinusoidal endothelial cells and hepatic microvasculature.

Conclusions Even 30 minutes of SELP after CS rescued DCD livers from ischemia-reperfusion injury, which may help the viability of the grafts.

Does short-term oxygenated subnormothermic perfusion prior to cold storage improve the viability of DCD livers in a rat model? The data show that subnormothermic ex vivo perfusion prevented liver from ischemia-reperfusion injury that may improve organ viability.

1 Department of Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.

2 Division of Transplantation and Regenerative Medicine, Tohoku University, Sendai, Japan.

Received 31 July 2017. Revision received 6 November 2017.

Accepted 9 November 2017.

This study was supported by a grant-in-aid for scientific research from the Ministry of Education, Science and Culture of Japan and the Ministry of Welfare of Japan and a Grant from Tohoku University Graduate School of Medicine.

The authors declare no conflicts of interest.

K.Y., M.S., S.K., K.M., W.N., T.K., H.Y., N.C., U.M., and K.T. participated in study design. K.Y. participated in the acquisition of data. K.Y. and M.S. participated in the analysis and interpretation. K.Y. drafted the article. G.M., K.T., and S.S. participated in the revision.

Correspondence: Yuta Kakizaki, MD, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan. (

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