**1. Introduction**

56 Liver Transplantation – Basic Issues

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Chatterjee, K. & Parmley, W. (2000). Comparative effects of pretreatment with captopril and losartan on cardiovascular protection in a rat model of ischemiaIschemia-reperfusion injury (IRI) is a series of multifaceted cellular events that takes place on the resumption of oxygen delivery to the affected organ after a period of hypoxia. IRI occurs in the liver during procedures that are associated with vascular inflow obstruction followed by restoration of blood flow, particularly during orthotopic liver transplantation. IRI can result in major hepatocellular damage.

In the last decade, nitric oxide (NO) has been shown to have various protective effects on cells during IRI. NO was first described as endothelium derived relaxing factor (EDRF), and it was described as being released from vascular endothelium to induce smooth muscle vasorelaxation. Since that time, much more has been elucidated about the role of NO in biological systems. NO has been demonstrated to inhibit oxidative stress, cytokine release, leukocyte endothelial adhesion and apoptosis (Phillips, Toledo, Lopez-Neblina, Anaya-Prado, & Toledo-Pereyra, 2009). On a cellular-signaling level, NO effects are mediated via redox-sensitive sites, and include: inhibition of protein kinase C, activation of tyrosine kinase, inactivation of NF-kB and activation of G proteins (Y. M. Kim, de Vera, Watkins, & Billiar, 1997). Previous studies have demonstrated that a reduction of NO during hepatic IRI, generally via a reduction in endothelial nitric oxide synthase (eNOS) activity, leads to liver injury (Köken & Inal, 1999). Inhaled NO or NO donor drugs are novel treatments that have been used clinically to attenuate liver IRI (Zaky, Siriussawakul, Tostenrud, Pauldine, & J. Lang, 2009). This review will discuss the pathophysiology of liver involvement during IRI and the clinical use of NO and its sister compounds in ameliorating the impact of liver IRI.
