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Histological changes during extracorporeal perfusions of the porcine liver: implications for temporary support during acute liver failures

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Abstract

Ex vivo perfused porcine livers have been used for temporary support during acute liver failure. The aim of this study was to assess both the histological changes and temporal pattern of the changes that occur during extracorporeal liver perfusions and to correlate these with factors that may influence them. Five porcine livers were harvested, preserved in cold ice and reperfused for 6 h in an extracorporeal circuit using autologous normothermic blood. Tissue biopsies were collected hourly. The Ishak score was used to quantify hepatic necrosis, and immunohistochemistry was used to evaluate apoptosis and regeneration. Liver weight, perfusion parameters, arterial blood gases and blood samples were also collected. The Ishak score peaked immediately before and 4 h after the start of reperfusion. Scattered necrosis, microvesicular steatotic vacuolization, sinusoidal dilatation and red cell extravasation were present. Anion gap acidosis was associated with the Ishak score. An inverse correlation was present between liver regeneration and necrosis, and between liver weight and regeneration. No changes were observed for apoptosis. Among the inflammatory cytokines evaluated, interleukin-6 and -8 levels increased significantly during the perfusions. Hepatic necrosis was always present during the extracorporeal perfusions, followed a definite pattern and was inversely correlated with regeneration. Apoptosis did not increase over baseline levels. The meaning of these findings and their correlation with clinical outcomes during acute hepatic failures deserve further investigation.

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Acknowledgments

The authors would like to acknowledge Lisa Wheatley for her invaluable technical support. Mr. Ashley R. Dennison had full access to all of the data in the study and accepts responsibility for the integrity of the data and the accuracy of the data analysis. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Hepatobiliary and Pancreatic Surgery, Leicester General Hospital, Gwendolen Road, Leicester, LE5 4PW, UK

    Gianpiero Gravante, Seok Ling Ong, Matthew S. Metcalfe & Ashley R. Dennison

  2. Department of Histopathology, University Hospitals of Leicester NHS Trust, Leicester, UK

    Angus McGregor

  3. Department of Human Physiology, Laboratory of Biometry, University of Tor Vergata, Rome, Italy

    Roberto Sorge

  4. Department of Hepatobiliary and Pancreatic Surgery, Royal Infirmary Hospital, Leicester, UK

    David M. Lloyd

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  1. Gianpiero Gravante
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  2. Seok Ling Ong
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  3. Angus McGregor
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  4. Roberto Sorge
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  5. Matthew S. Metcalfe
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  7. Ashley R. Dennison
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Correspondence to Gianpiero Gravante or Seok Ling Ong.

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Gravante, G., Ong, S.L., McGregor, A. et al. Histological changes during extracorporeal perfusions of the porcine liver: implications for temporary support during acute liver failures. J Artif Organs 16, 218–228 (2013). https://doi.org/10.1007/s10047-012-0677-x

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  • DOI: https://doi.org/10.1007/s10047-012-0677-x

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