Liver ischemia-reperfusion injury: From trigger loading to shot firing

Author:

Felli Eric12ORCID,Felli Emanuele3ORCID,Muttillo Edoardo M.4ORCID,Urade Takeshi5,Laracca Giovanni G.4,Giannelli Valerio6,Famularo Simone789,Geny Bernard10,Ettorre Giuseppe M.6,Rombouts Krista11ORCID,Pinzani Massimo11ORCID,Diana Michele9ORCID,Gracia-Sancho Jordi1212ORCID

Affiliation:

1. Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital, University of Bern, Switzerland

2. Department for BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland

3. Department of Digestive Surgery and Liver Transplantation, University Hospital of Tours, France

4. Department of Medical Surgical Science and Translational Medicine, Sant’ Andrea Hospital, Sapienza University of Rome, Rome, Italy

5. Department of Surgery, Division of Hepato-Biliary-Pancreatic Surgery, Kobe University Graduate School of Medicine, Japan

6. Department of Transplantation and General Surgery, San Camillo Hospital, Italy

7. Department of Biomedical Science, Humanitas University Pieve Emanuele, Italy

8. Department of Hepatobiliary and General Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy

9. Research Institute Against Cancer of the Digestive System (IRCAD), France

10. Institute of Physiology, EA3072 Mitochondria Respiration and Oxidative Stress, University of Strasbourg, France

11. University College London - Institute for Liver and Digestive Health, Royal Free Hospital, NW3 2PF London, United Kingdom

12. Liver Vascular Biology Research Group, IDIBAPS Biomedical Research Institute, Hospital Clínic Barcelona, CIBEREHD, Barcelona, Spain

Abstract

An ischemia-reperfusion injury (IRI) results from a prolonged ischemic insult followed by the restoration of blood perfusion, being a common cause of morbidity and mortality, especially in liver transplantation. At the maximum of the potential damage, IRI is characterized by 2 main phases. The first is the ischemic phase, where the hypoxia and vascular stasis induces cell damage and the accumulation of damage-associated molecular patterns and cytokines. The second is the reperfusion phase, where the local sterile inflammatory response driven by innate immunity leads to a massive cell death and impaired liver functionality. The ischemic time becomes crucial in patients with underlying pathophysiological conditions. It is possible to compare this process to a shooting gun, where the loading trigger is the ischemia period and the firing shot is the reperfusion phase. In this optic, this article aims at reviewing the main ischemic events following the phases of the surgical timeline, considering the consequent reperfusion damage.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Transplantation,Hepatology,Surgery

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