**6.1.1 Trimetazidine and AICAR**

Trimetazidine (TMZ), which has been used as an anti-ischemic drug in the heart for over 35 years (Ikizler et al., 2003) reduced liver injury and improved liver regeneration and survival rate in partial hepatectomy under vascular occlusion (Casillas et al., 2006). TMZ has been used as an additive in UW solution to protect steatotic livers exposed to prolonged cold ischemia in an *ex vivo* model of hepatic ischemia (Ben Mosbah et al., 2006). This could be of interest since irreversible injury has been reported in liver grafts preserved in UW after prolonged cold ischemic periods (between 16 h to 24 h) (Ben Mosbah et al., 2006). Studies examining the underlying protective mechanisms of TMZ suggest that mitochondria, energy metabolism, oxidative stress and microcirculation might be important targets through which TMZ exerts its cytoprotective effect (Ben Mosbah et al., 2006; Ikizler et al., 2003). Interestingly, these mechanisms are responsible for the vulnerability of steatotic livers to I/R. Similarly to the benefits of TMZ, the addition of AMPK activators to UW solutions such as 5-amino-4-imidazole carboxamide riboside (AICAR), protected steatotic livers against their vulnerability to I/R. TMZ, by means of AMPK, increased NO, thus protecting steatotic livers against their vulnerability to I/R injury (Ben Mosbah et al., 2006, 2007; Carrasco et al., 2005). Taking these observations into account, TMZ and AICAR may constitute new additives to UW solution in steatotic liver preservation, whereas a combination of both seems unnecessary.
