Past and future approaches to ischemia-reperfusion lesion associated with liver transplantation

Ischemia-reperfusion (I/R) injury associated with liver transplantation remains a serious complication in clinical practice, in spite of several attempts to solve the problem. The present review focuses on the complexity of I/R injury, summarizing conflicting results obtained from the literature about the mechanisms responsible for it. We also review the therapeutic strategies designed in past years to reduce I/R injury, attempting to explain why most of them have not been applied clinically. These strategies include improvements in pharmacological treatments, modifications of University of Wisconsin (UW) preservation solution based on a variety of additives, and gene therapy. Finally, we will consider new potential protective strategies using trimetazidine, 5-amino-4-imidazole carboxamide riboside (AICAR), melatonin, modulators of the renin-angiotensin system (RAS) and the phosphatidylinositol-3-OH kinase (PI3K)-Akt and the p42/p44 extracellular signal-regulated kinases (Erk 1/2) pathway. These strategies have shown promising results for I/R injury but have not been tested in experimental liver transplantation to date. Moreover, we will review ischemic preconditioning, taking into account the recent clinical studies that suggest that this surgical strategy could be appropriate for liver transplantation. © 2006 Elsevier Inc. All rights reserved.Supported by the Ministerio de Educación y Ciencia (project grants BFI 2003-00912, SAF 2005-00385, and Ramón y Cajal research contract for Carmen Peralta) (Madrid, Spain), Ministerio de Asuntos Exteriores (hp2003-0051) and Generalitat de Catalunya (2005SGR/00781 project. We would also like to thank the CONACYT (Mexico D.F., Mexico), AECI (Madrid, Spain) and CAPES Ministério de Educaçao (Brasília, Brazil) for the fellowships awarded to A. Casillas-Ramírez, I. Ben Mosbah and Fernando Ramalho, respectivelyPeer Reviewe