The effects of remote ischemic pre-conditioning in reducing liver injury in a rabbit model and in patients

Ischemia reperfusion injury (IRI) following liver transplantation and major liver surgery results in a systemic inflammatory response syndrome (SIRS) with damage to the liver and remote organs. Physical methods of reducing liver IRI such as direct ischemic pre-conditioning (IPC) where a brief period of IRI is applied to the liver have been shown to reduce the adverse effects of liver IRI. However, direct liver IPC has been shown to impair liver regeneration in experimental models. Remote ischemic preconditioning (RIPC) is a novel strategy for reducing IRI through a brief period of IPC to a remote organ and this has been shown to reduce IRI to the heart and other organs. The purpose of the experiments described in this thesis is to investigate the effect and mechanism of RIPC in reducing liver IRI in an animal model and in patients. A rabbit model of total hepatic ischemia was established to study early warm liver IRI and in this model 25 minute of total portal inflow occlusion resulted in severe liver IRI at 2 hours of reperfusion. In the main experimental study rabbits were divided into four equal groups to study the effect of RIPC on early phase (2 hours) warm IRI following total portal inflow occlusion. RIPC before IRI reduced the adverse local and systemic effects of IRI, reduced acidosis and nitric oxide was shown to be an important mediator of protection. In a proof of concept study 16 patients undergoing major liver resection surgery were randomised into two groups, control and RIPC. In the RIPC group, post resection, there was a reduction in liver IRI