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Validation of a surgical model for posthepatectomy liver failure in rats
Andrea Lund1, Michelle Meier1, Kasper Jarlhelt Andersen1
1Aarhus University Hospital, Department of Upper Gastrointestinal and Hepato-Pancreato-Biliary Surgery, Aarhus N, Denmark.
Background:
The upper limit for liver resections in rats is approximately 90%. In the early postoperative phase, mortality increases. The aim of the present study was to validate the rat model of 90% partial hepatectomy (PH) as a model of post-hepatectomy liver failure (PHLF). Further, we wanted to test a quantitative scoring system as a detector of lethal outcomes caused by PHLF in rats.
Methods:
Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further, block randomization was performed based on time of euthanization: 12, 24, or 48 h after surgery. A general distress score (GDS) ≥10 during the day or ≥6 at midnight prompted early euthanization and classification as nonsurvivor. Animals euthanized as planned were classified as survivors. During euthanization, blood and liver tissue were collected, and liver-specific biochemistry was evaluated.
Results:
Based on the biochemical results, all animals subjected to 90% PH experienced PHLF. Seventeen rats were euthanized due to irreversible PHLF. The GDS increased for nonsurvivors within 12-18 h after surgery. The mean time for euthanization was 27 h after surgery.
Conclusion:
Based on the GDS and liver-specific biochemistry, we concluded that the model of 90% PH seems to be a proper model for investigating PHLF in rats. As a high GDS is associated with increased mortality, the GDS appears to be valuable in detecting lethal outcomes caused by PHLF in rats.