Remote postconditioning may attenuate ischaemia-reperfusion injury in the murine hindlimb through adenosine receptor activation

Eur J Vasc Endovasc Surg. 2010 Dec;40(6):804-9. doi: 10.1016/j.ejvs.2010.08.014. Epub 2010 Sep 24.


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.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Edema / etiology
  • Hindlimb
  • Ischemic Postconditioning*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Muscle, Skeletal / blood supply*
  • Muscle, Skeletal / metabolism*
  • Muscle, Skeletal / pathology
  • Necrosis
  • Neutrophil Infiltration
  • Purinergic P1 Receptor Antagonists / pharmacology
  • Receptors, Purinergic P1 / drug effects
  • Receptors, Purinergic P1 / metabolism*
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / prevention & control*
  • Signal Transduction* / drug effects
  • Time Factors
  • Tourniquets


  • Purinergic P1 Receptor Antagonists
  • Receptors, Purinergic P1