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World J Gastrointest Surg. Sep 27, 2023; 15(9): 1858-1870
Published online Sep 27, 2023. doi: 10.4240/wjgs.v15.i9.1858
Hepatic ischemia-reperfusion syndrome and its effect on the cardiovascular system: The role of treprostinil, a synthetic prostacyclin analog
Christina Mouratidou, Efstathios T Pavlidis, Georgios Katsanos, Serafeim-Chrysovalantis Kotoulas, Eleni Mouloudi, Georgios Tsoulfas, Ioannis N Galanis, Theodoros E Pavlidis
Christina Mouratidou, Serafeim-Chrysovalantis Kotoulas, Eleni Mouloudi, Intensive Care Unit, Hippokration General Hospital, Thessaloniki 54642, Greece
Efstathios T Pavlidis, Ioannis N Galanis, Theodoros E Pavlidis, 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
Georgios Katsanos, Georgios Tsoulfas, Department of Transplantation, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Thessaloniki 54642, Greece
Author contributions: Mouratidou C, Pavlidis ET, Katsanos G, and Tsoulfas G designed and performed the research; Mouratidou C, Pavlidis ET, Katsanos G, Kotoulas SC, Mouloudi E, Tsoulfas G, and Galanis IN analyzed data; Kotoulas SC, Mouloudi E, and Galanis IN contributed new analytic tools; Kotoulas SC, Mouloudi E, Tsoulfas G, Galanis IN, and Pavlidis TE reviewed the paper; Pavlidis TE approved the paper.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Theodoros E Pavlidis, Doctor, PhD, Full Professor, Surgeon, 2nd Propedeutic Department of Surgery, Hippokration General Hospital, School of Medicine, Aristotle University of Thessaloniki, Konstantinoupoleos 49, Thessaloniki 54642, Greece. pavlidth@auth.gr
Received: June 9, 2023
Peer-review started: June 9, 2023
First decision: July 18, 2023
Revised: July 20, 2023
Accepted: July 25, 2023
Article in press: July 25, 2023
Published online: September 27, 2023
Processing time: 104 Days and 21.4 Hours
Abstract

Hepatic ischemia-reperfusion syndrome has been the subject of intensive study and experimentation in recent decades since it is responsible for the outcome of several clinical entities, such as major hepatic resections and liver transplantation. In addition to the organ’s post reperfusion injury, this syndrome appears to play a central role in the dysfunction of distant tissues and systems. Thus, continuous research should be directed toward finding effective therapeutic options to improve the outcome and reduce the postoperative morbidity and mortality rates. Treprostinil is a synthetic analog of prostaglandin I2, and its experimental administration has shown encouraging results. It has already been approved by the Food and Drug Administration in the United States for pulmonary arterial hypertension and has been used in liver transplantation, where preliminary encouraging results showed its safety and feasibility by using continuous intravenous administration at a dose of 5 ng/kg/min. Treprostinil improves renal and hepatic function, diminishes hepatic oxidative stress and lipid peroxidation, reduces hepatictoll-like receptor 9 and inflammation, inhibits hepatic apoptosis and restores hepatic adenosine triphosphate (ATP) levels and ATP synthases, which is necessary for functional maintenance of mitochondria. Treprostinil exhibits vasodilatory properties and antiplatelet activity and regulates proinflammatory cytokines; therefore, it can potentially minimize ischemia-reperfusion injury. Additionally, it may have beneficial effects on cardiovascular parameters, and much current research interest is concentrated on this compound.

Keywords: Hepatic ischemia-reperfusion syndrome; Myocardial damage; Prostaglandins; Treprostinil; Liver transplantation; Hepatectomy

Core Tip: End-stage liver disease is one of the leading causes of morbidity and mortality worldwide. The role of liver transplantation and liver resection in malignant disease has changed over the last decades with the evolution of high-risk surgical techniques and the great improvement in long-term survival. However, hepatic ischemia-reperfusion syndrome remains a significant clinical problem, as it is the main reason for postoperative liver failure and multiple organ dysfunction. Treprostinil is a synthetic analog of prostaglandin I2 with potential protective effects against ischemia-reperfusion injury. We herein discuss the effect of hepatic ischemia-reperfusion syndrome on the cardiovascular system and the role of treprostinil as a new promising therapeutic option.