Direct, remote and combined ischemic conditioning in liver surgery

Liver ischemia-reperfusion injury is a major cause of postoperative liver dysfunction, morbidity and mortality following liver resection and transplantation. Ischemic conditioning has been shown to ameliorate ischemia-reperfusion injury in small animal models. It can be applied directly or remotely when cycles of ischemia and reperfusion are applied to a distant site or organ. Considering timing of the procedure, different protocols are available. Ischemic preconditioning refers to that performed before the duration of ischemia of the target organ. Ischemic perconditioning is performed over the duration of ischemia of the target organ. Ischemic postconditioning applies brief episodes of ischemia at the onset of reperfusion following a prolonged ischemia. Animal studies pointed towards suppressing cytokine release, enhancing the production of hepatoprotective adenosine and reducing liver apoptotic response as the potential mechanisms responsible for the protective effect of direct tissue conditioning. Interactions between neural, humoral and systemic pathways all lead to the protective effect of remote ischemic preconditioning. Despite promising animal studies, none of the aforementioned protocols proved to be clinically effective in liver surgery with the exception of morbidity reduction in cirrhotic patients undergoing liver resection. Further human clinical trials with application of novel conditioning protocols and combination of methods are warranted before implementation of ischemic conditioning in day-to-day clinical practice.