Portal hyperperfusion: Mechanism of injury and stimulus for regeneration in porcine small-for-size transplantation

Authors

  • Constantino Fondevila,

    Corresponding author
    1. Department of Surgery, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
    • Liver Transplant Unit, Department of Surgery, Hospital Clinic, University of Barcelona, C/Villarroel 170, 08036 Barcelona, Spain
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    • Telephone: +34 932 272 339; FAX: +34 932 275 739

  • Amelia J. Hessheimer,

    1. Department of Surgery, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • Pilar Taurá,

    1. Department of Anesthesia, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • Olga Sánchez,

    1. Department of Surgery, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • David Calatayud,

    1. Department of Surgery, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • Nicolas de Riva,

    1. Department of Anesthesia, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • Javier Muñoz,

    1. Department of Surgery, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • Jose Fuster,

    1. Department of Surgery, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • Antoni Rimola,

    1. Liver Unit, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • Juan C. García-Valdecasas

    1. Department of Surgery, Institute of Digestive Diseases, Hospital Clinic, Network Center for Biomedical Research in Hepatic and Digestive Diseases, August Pi i Sunyer Institute for Biomedical Research, University of Barcelona, Barcelona, Spain
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  • This work was supported by FIS (Fondo de Investigacion Sanitaria) grant 04/1238 from the Carlos III Institute of Health (Ministry of Health and Consumption). Amelia J. Hessheimer was supported by grants from the BBVA (Banco Bilbao Vizcaya Argentaria) Foundation and the Vanderbilt Medical School Medical Scholars Program. David Calatayud was supported by a grant from the Catalan Foundation of Transplantation.

Abstract

Understanding the pathogenesis of small-for-size (SFS) syndrome is critical to expanding the applicability of partial liver transplantation. We aimed to characterize its acute presentation and association with alterations in hepatic hemodynamics, microstructure, and regeneration in a porcine model. Eighteen SFS liver transplants were performed. Donors underwent 70% hepatectomy. Partial grafts were implanted into larger recipients. Whole liver transplants were also performed (n = 6). Recipients were followed until death or for 5 days. Hemodynamics were measured, and tissue was sampled intraoperatively and at the study end. Serum was sampled regularly during follow-up. Seventeen SFS transplants and 6 whole liver transplants were included. SFS grafts represented 23.2% (19.3%-25.3%) of the recipients' standard liver volume. The survival rate was 29% and 100% in the SFS and whole liver groups, respectively. The portal venous flow, pressure gradient, and resistance were significantly higher in recipients of SFS grafts versus whole livers after portal and arterial reperfusion. Arterial flow as a percentage of the total liver blood flow was significantly lower after reperfusion in SFS grafts and remained so when measured again after 5 days. Markers of endothelial cell injury increased soon after reperfusion, and those of hepatocellular injury increased later; both predicted the appearance of either graft failure or histological recovery. Proliferative activity peaked earlier and higher among nonsurvivors in the SFS group. Surviving grafts demonstrated a slower but maintained rise in regenerative activity, although metabolic activity failed to improve. In SFS transplantation in the acute setting, portal hyperperfusion is a stimulus for regeneration but may simultaneously cause irreparable endothelial injury. This porcine model not only helps to elucidate the inciting factors in SFS pathogenesis but also offers a clinically relevant means to study its prevention. Liver Transpl 16:364–374, 2010. © 2010 AASLD.

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