title: Remote ischaemic preconditioning by brief hind limb ischaemia protects against renal ischaemia-reperfusion injury: the role of adenosine.
abstract: BACKGROUND
  Remote ischaemic preconditioning (RIPC) is a strategy to protect a target organ against ischaemia-reperfusion injury (IRI) by inducing short-term ischaemia/reperfusion (I/R) in a remote organ. RIPC of the kidney by temporary limb occlusion would be a safe, inexpensive and noninvasive method to prevent renal damage in, e.g., transplantation and aortic surgery. We investigated whether brief hind limb occlusion can protect against renal IRI and whether this protection is adenosine dependent.
  
  
  METHODS
  Rats underwent either no RIPC, unilateral RIPC or bilateral RIPC. The preconditioning stimulus was either continuous (12'/12' I/R) or fractionated (three times 4'/4' I/R). After the last reperfusion period, we induced 25' ischaemia in the right kidney.
  
  
  RESULTS
  After 24 h of reperfusion, renal function was improved by 30-60% in both bilateral RIPC groups and in the fractionated unilateral group. Renal tubule damage and kidney injury molecule-1 expression were reduced in three of four RIPC groups. Treatment with the adenosine receptor blocker 8-(p-sulfophenyl)theophylline had no effect on fractionated or continuous RIPC.
  
  
  CONCLUSIONS
  Brief hind limb ischaemia induces protection against renal IRI, which makes this a promising strategy to prevent renal IRI in a clinical setting. Bilateral RIPC was more effective than unilateral RIPC, and this protection occurs via an adenosine-independent mechanism.
authors.affiliation: Department of Pharmacology and Toxicology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands. k.wever@pharmtox.umcn.nl
authors.forename: Kimberley E
authors.initials: KE
authors.lastname: Wever
authors.forename: Michiel C
authors.initials: MC
authors.lastname: Warlé
authors.forename: Frank Adtg
authors.initials: FA
authors.lastname: Wagener
authors.forename: José W
authors.initials: JW
authors.lastname: van der Hoorn
authors.forename: Rosalinde
authors.initials: R
authors.lastname: Masereeuw
authors.forename: J Adam
authors.initials: JA
authors.lastname: van der Vliet
authors.forename: Gerard A
authors.initials: GA
authors.lastname: Rongen
mesh_terms: D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D006614:Hindlimb / Q000503:physiopathology*; D019194:Ischemic Preconditioning; D007668:Kidney / Q000098:blood supply* / Q000473:pathology; D008297:Male; D058915:Purinergic P1 Receptor Antagonists / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D058915:Purinergic P1 Receptor Antagonists; C031433:8-(4-sulfophenyl)theophylline; D013806:Theophylline; D000241:Adenosine