Biochemical and morphological responses to post-hepatectomy liver failure in rats

Andrea Lund; Kasper Jarlhelt Andersen; Michelle Meier; Marie Ingemann Pedersen; Anders Riegels Knudsen; Jakob Kirkegård; Frank Viborg Mortensen; Jens Randel Nyengaard

doi:10.1038/s41598-023-40736-y

Biochemical and morphological responses to post-hepatectomy liver failure in rats

Andrea Lund^*, Kasper Jarlhelt Andersen, Michelle Meier, Marie Ingemann Pedersen^*, Anders Riegels Knudsen, Jakob Kirkegård, Frank Viborg Mortensen, Jens Randel Nyengaard

^*Corresponding author for this work

Department of Clinical Medicine - The Department of Surgical Gastroenterology
Department of Clinical Medicine - Core Centre for Molecular Morphology, Section for Stereology and Microscopy
Department of Clinical Medicine - The Department of Pathology

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

2 Citations (Scopus)

Abstract

The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.

Original language	English
Article number	13544
Journal	Scientific Reports
Volume	13
Issue	1
ISSN	2045-2322
DOIs	https://doi.org/10.1038/s41598-023-40736-y
Publication status	Published - Aug 2023

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title = "Biochemical and morphological responses to post-hepatectomy liver failure in rats",

abstract = "The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.",

author = "Andrea Lund and Andersen, {Kasper Jarlhelt} and Michelle Meier and Pedersen, {Marie Ingemann} and Knudsen, {Anders Riegels} and Jakob Kirkeg{\aa}rd and Mortensen, {Frank Viborg} and Nyengaard, {Jens Randel}",

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AU - Lund, Andrea

AU - Andersen, Kasper Jarlhelt

AU - Meier, Michelle

AU - Pedersen, Marie Ingemann

AU - Knudsen, Anders Riegels

AU - Kirkegård, Jakob

AU - Mortensen, Frank Viborg

AU - Nyengaard, Jens Randel

PY - 2023/8

Y1 - 2023/8

N2 - The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.

AB - The upper limit for partial hepatectomy (PH) in rats is 90%, which is associated with an increased risk of post-hepatectomy liver failure (PHLF), correlating with high mortality. Sixty-eight rats were randomized to 90% PH, sham operation, or no surgery. Further block randomization was performed to determine the time of euthanasia, whether 12, 24, or 48 h after surgery. A general distress score (GDS) was calculated to distinguish between rats with reversible (GDS < 10) and irreversible PHLF (GDS ≥ 10). At euthanasia, the liver remnant and blood were collected. Liver-specific biochemistry and regeneration ratio were measured. Hepatocyte proliferation and volume were estimated using stereological methods. All rats subjected to 90% experienced biochemical PHLF. The biochemical and morphological liver responses did not differ between the groups until 48 h after surgery. At 48 h, liver regeneration and function were significantly improved in survivors. The peak mean regeneration ratio was 15% for rats with irreversible PHLF compared to 26% for rats with reversible PHLF. The 90% PH rat model was associated with PHLF and high mortality. Irreversible PHLF was characterized by impaired liver regeneration capacity and an insufficient ability to metabolize ammonia.

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Biochemical and morphological responses to post-hepatectomy liver failure in rats

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