Published online Dec 8, 2016. doi: 10.4254/wjh.v8.i34.1489
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
Processing time: 221 Days and 4.1 Hours
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.
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.