Remote Postconditioning may Attenuate Ischaemia–Reperfusion Injury in the Murine Hindlimb Through Adenosine Receptor Activation

Abstract

Objective This study aimed to determine the effect and mechanisms of remote postconditioning (RPC) upon ischaemia–reperfusion injury (IRI) in the ischaemic mouse hindlimb. Design RPC is the brief application of ischaemia to remote organs immediately before reperfusion of an ischaemic target organ, and it is a novel approach to IRI attenuation. Materials and methods Right hindlimb ischaemia was induced in mice using a rubber tourniquet, the release of which initiated reperfusion. We established RPC by 5 min of ischaemia followed by 5 min of reperfusion in the left hindlimb immediately before right hindlimb reperfusion. The wet/dry ratio of skeletal muscle (degree of tissue oedema), myeloperoxidase (MPO) activity (accumulation of neutrophils), and nitroblue tetrazolium reduction (tissue necrosis) were evaluated. We also intra-peritoneally injected 8-sulphophenyltheophylline (SPT), an adenosine receptor inhibitor, in RPC mice. Results Wet/dry ratio, MPO activity and tissue necrosis were significantly lower in the RPC group than in the control group, and injection of SPT impaired the protective effect of RPC. Conclusions Our results show that RPC attenuated IRI in murine hindlimb ischaemia, possibly through endogenous adenosine receptor activation, and that RPC might serve as a promising therapeutic option for treating serious limb ischaemia.