Abstract 5561: Remote Postconditioning May Attenuate Ischemia-reperfusion Injury in a Murine Hind Limb Through Activation of Adenosine Receptors

Abstract

Introduction: Preconditioning is a potent protection from ischemia-reperfusion injury (IRI), but its clinical application has been limited because preconditioning must be established before unanticipated ischemic events. Remote postconditioning (RPC), an application of brief ischemia in remote organs just before reperfusion of ischemic target organ, is a novel approach to attenuate IRI. However, its efficacy and possible mechanisms in IRI of ischemic limb has not been elucidated. Methods: Right hind limb ischemia was induced using a rubber tourniquet, and reperfusion was initiated by releasing the tourniquet. RPC was established by 5 minutes’ ischemia followed by 5 minutes’ reperfusion in the left leg just before reperfusion of the right leg. Control mice received ischemia for 3 hours followed by 24 hours reperfusion; RPC mice received ischemia for 3 hours followed by 24 hours reperfusion accompanying with two sets of RPC. After 24 hours of reperfusion, wet/dry ratio of skeletal muscle (degree of tissue edema), myeloperoxidase (MPO) activity (accumulation of neutrophil), and nitro blue tetrazolium (NBT) reduction (tissue necrosis) were evaluated. In addition, 8-sulfophenyltheophylline (SPT), an inhibitor of adenosine receptors, was intraperitonealy injected to mice with or without RPC. NBT reduction was measured to evaluate possible mechanisms. Results: Wet/dry ratio, MPO activity and tissue necrosis were significantly lower in RPC group than control group, and injection of SPT impaired the protective effect of RPC (table ). Conclusion: RPC attenuated IRI in a murine hind limb ischemia, possibly through the endogenous activation of adenosine receptors. RPC may be promising therapeutic option to treat serious limb ischemia.