Masuo H, Shimizu A, Motoyama H, Kubota K, Notake T, Yoshizawa T, Hosoda K, Yasukawa K, Kobayashi A, Soejima Y. Impact of endothelial nitric oxide synthase activation on accelerated liver regeneration in a rat ALPPS model. World J Gastroenterol 2023; 29(5): 867-878 [PMID: 36816620 DOI: 10.3748/wjg.v29.i5.867]
Corresponding Author of This Article
Akira Shimizu, MD, PhD, Associate Professor, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan. ashimizu@shinshu-u.ac.jp
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
Basic Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Hitoshi Masuo, Akira Shimizu, Hiroaki Motoyama, Koji Kubota, Tsuyoshi Notake, Takahiro Yoshizawa, Kiyotaka Hosoda, Koya Yasukawa, Akira Kobayashi, Yuji Soejima, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, Matsumoto 390-8621, Japan
Author contributions: Masuo H, Motoyama H, Yoshizawa T, Hosoda K, and Yasukawa K contributed to the acquisition and analysis of experimental data and drafting of the manuscript; Shimizu A, Kubota K, Notake T, Kobayashi A, and Soejima Y contributed to the conception and design of the study and made critical revisions related to the important intellectual content of the manuscript; and all authors have provided final approval for the version of the manuscript for submission.
Supported bythe JSPS KAKENHI, JP17K10664.
Institutional animal care and use committee statement: Based on national and institutional regulations and guidelines, all procedures for animal experiments were reviewed by the Committee for Animal Experiments and approved by the President of Shinshu University (Approval numbers 270018 and 019067).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Corresponding author: Akira Shimizu, MD, PhD, Associate Professor, Division of Gastroenterological, Hepato-Biliary-Pancreatic, Transplantation and Pediatric Surgery, Department of Surgery, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto 390-8621, Japan. ashimizu@shinshu-u.ac.jp
Received: October 29, 2022 Peer-review started: October 29, 2022 First decision: November 30, 2022 Revised: December 7, 2022 Accepted: January 11, 2023 Article in press: January 11, 2023 Published online: February 7, 2023 Processing time: 94 Days and 5.4 Hours
ARTICLE HIGHLIGHTS
Research background
Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) has already been clinically applied in various countries. Although it has been reported that ALPPS offers faster and larger liver regeneration compared to portal vein embolization (PVE), the mechanism of this phenomenon is still unclear.
Research motivation
The aim of this study was to investigate the underlying mechanism of rapid liver regeneration after ALPPS focusing on inflammatory cytokines and endothelial nitric oxide synthase (eNOS) activation.
Research objectives
Activation of eNOS was considered one of key points on mechanism of rapid liver regeneration after ALPPS.
Research methods
Liver regeneration was compared between the rat portal vein ligation (PVL) model and the rat ALPPS model. In addition, impact of administration of gadolinium chloride (GdCl3, Kupffer cell inhibitor), NG-nitro-arginine methyl ester (L-NAME, NOS inhibitor), and molsidomine (NO enhancer) on liver regeneration after PVL and/or ALPPS.
Research results
Administration of GdCl3 before ALPPS provided no significant negative influence of liver regeneration after ALPPS. Administration of L-NAME before ALPPS suppressed liver regeneration after ALPPS, while administration of molsidomine before PVL accerelated liver regeneration after PVL as well as ALPPS.
Research conclusions
ALPPS is an alternative to PVE for reducing posthepatectomy liver failure after major hepatectomy.
Research perspectives
Combination of NO-producing agents and less invasive procedure can be an alternative to ALPPS procedure in the future.
