Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Dec 8, 2016; 8(34): 1489-1496
Published online Dec 8, 2016. doi: 10.4254/wjh.v8.i34.1489
Role of nitric oxide in liver transplantation: Should it be routinely used?
Kyota Fukazawa, John D Lang
Kyota Fukazawa, Division of Transplant Anesthesiology, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, United States
John D Lang, Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, United States
Author contributions: Both authors contributed to the manuscript.
Conflict-of-interest statement: No relevant conflicts of interest were declared for each author.
Open-Access: 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:
Correspondence to: John D Lang, MD, Associate Professor, Department of Anesthesiology and Pain Medicine, University of Washington, 1959 NE Pacific Street, Seattle, WA 98195, United States.
Telephone: +1-206-5432673 Fax: +1-206-5432958
Received: April 29, 2016
Peer-review started: May 4, 2016
First decision: July 4, 2016
Revised: August 6, 2016
Accepted: October 17, 2016
Article in press: October 18, 2016
Published online: December 8, 2016

Ischemia-reperfusion injury (IRI) continues to be a major contributor to graft dysfunction, thus supporting the need for therapeutic strategies focused on minimizing organ damage especially with growing numbers of extended criteria grafts being utilized which are more vulnerable to cold and warm ischemia. Nitric oxide (NO·) is highly reactive gaseous molecule found in air and regarded as a pollutant. Not surprising, it is extremely bioactive, and has been demonstrated to play major roles in vascular homeostasis, neurotransmission, and host defense inflammatory reactions. Under conditions of ischemia, NO· has consistently been demonstrated to enhance microcirculatory vasorelaxation and mitigate pro-inflammatory responses, making it an excellent strategy for patients undergoing organ transplantation. Clinical studies designed to test this hypothesis have yielded very promising results that includes reduced hepatocellular injury and enhanced graft recovery without any identifiable complications. By what means NO· facilitates extra-pulmonary actions is up for debate and speculation. The general premise is that they are NO· containing intermediates in the circulation, that ultimately mediate either direct or indirect effects. A plethora of data exists explaining how NO·-containing intermediate molecules form in the plasma as S-nitrosothiols (e.g., S-nitrosoalbumin), whereas other compelling data suggest nitrite to be a protective mediator. In this article, we discuss the use of inhaled NO· as a way to protect the donor liver graft against IRI in patients undergoing liver transplantation.

Keywords: Liver, Nitric oxide, Ischemia-reperfusion, Nitrite, Transplantation

Core tip: Our manuscript assesses the basic and clinical literature of nitric oxide and liver transplantation and creates a scientific/clinical justification for its routine use.