**2.1 IPC in experimental models**

*Liver Disease and Surgery*

of the population and consequently a further increase in the number of steatotic livers submitted to surgery is to be expected [5]. These observations highlight the

The mechanisms involved in liver I/R injury are complicated, mainly including microcirculation failure and oxidative stress [4]. A wide range of strategies has been attempted in order to mitigate I/R injury, mainly pharmacological treatments focused on gene therapy, improvement of preservation solutions, among others. However, an effective treatment is still lacking [4] since is difficult to achieve by targeting individual mechanism. Surgical strategies such as the ischemic preconditioning (IPC) technique noted for its effectiveness, as it activates several protective pathways against I/R injury in experimental models should be considered. IPC can be either applied directly to the target organ [6] or remotely (RIPC) to a distant vascular bed [7]. The benefits of the IPC and RIPC observed in experimental models of hepatic warm and cold ischemia [8, 9] prompted human trials of ischemic preconditioning. However, controversial results have been showed in the clinical practice. Therefore, the present chapter aims to describe the current knowledge of the IPC and RIPC in liver resections and liver transplantation of both steatotic and non-steatotic livers. In addition, the scientific controversies regarding the possible beneficial effects of these techniques, in experimental, translational and clinical

Preconditioning the liver with ischemia involves a brief period of portal triad clamping usually between 5 and 15 min followed by a brief period of reperfusion (10–20 min) before a prolonged period of ischemia [10] (**Figure 1**). The exact mode of action of the IPC in the prevention of post-operative hepatic complication has not yet been fully comprehended. The molecular basis for IPC consists of a sequence of events in which in response to the triggers of IPC, a signal must be generated and transduced into an intracellular message leading to the effector mechanism

need to develop protective strategies in liver surgical conditions.

studies in the setting of liver surgery will be discussed.

*Schematic illustration of ischemic preconditioning and remote ischemic preconditioning.*

**2. Ischemic preconditioning**

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**Figure 1.**

Over the years, studies with experimental animal models have reported numerous positive effects of IPC on the alleviation of hepatic I/R injury and improvements of post-operative liver functioning. Various combinations of ischemia and reperfusion periods have been tested showing similar beneficial effects: lower aminotransferase levels, reduced hepatocellular injury, and higher survival rates [14]. IPC protected against mitochondrial ROS and thus reduce the oxidative stressmediated damage in liver I/R injury [15–18]. However, Rüdiger et al. showed that IPC is beneficial in liver submitted to an ischemic period of up to 75 min, but not for more prolonged ischemia [19].
