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

Abstract

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.

• Authors: Yuta Kakizaki, Shigehito Miyagi, Kenji Shimizu, Koji Miyazawa, Wataru Nakanishi, Kazuaki Tokodai, Yasuyuki Hara, Chikashi Nakanishi, Michiaki Unno, Takashi Kamei, Masafumi Goto, Susumu Satomi
• Journal: Transplantation (Transplantation) Vol. 102 Issue 4 Pg. e147-e154 (04 2018) ISSN: 1534-6080 [Electronic] United States
• PMID: 29309377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Oxygen

Topics

• Animals
• Apoptosis
• Cold Ischemia (adverse effects)
• Cold Temperature (adverse effects)
• Energy Metabolism
• Liver (blood supply, metabolism, surgery, ultrastructure)
• Liver Transplantation (adverse effects, methods)
• Male
• Models, Animal
• Organ Preservation (adverse effects, methods)
• Oxygen (metabolism)
• Perfusion (adverse effects, methods)
• Primary Graft Dysfunction (etiology, metabolism, pathology, prevention & control)
• Rats, Wistar
• Time Factors
• Tissue Survival
• Tissue and Organ Harvesting (adverse effects, methods)