title: Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart.
abstract: OBJECTIVE
  The aim of this study was to determine whether selective activation of the adenosine A3 receptor reduces infarct size in a Langendorff model of myocardial ischemia-reperfusion injury.
  
  
  METHODS
  Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion. Infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR).
  
  
  RESULTS
  Preconditioning by 5 min global ischemia and 10 min reperfusion reduced infarct size (IA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A3-selective agonist, IB-MECA (A3 Ki: 2 nM; A1 Ki: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A1-selective agonist, R-PIA (25 nM) reduced IA/AAR to a similar extent (21 +/- 6%). However, while the cardioprotective effect of R-PIA was significantly inhibited (54 +/- 7% IA/AAR) by the rabbit A1-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A1 vs. A3) concentration of BWA1433 (5 microM) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR).
  
  
  CONCLUSIONS
  These data clearly demonstrate that selective A3 receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A3-dependent cardioprotection is similar to that provided by A1 receptor stimulation or ischemic preconditioning.
authors.affiliation: Department of Cardiovascular and Metabolic Diseases, Pfizer Inc., Groton, CT 06340, USA. w_ross_tracey@groton.pfizer.com
authors.forename: W R
authors.initials: WR
authors.lastname: Tracey
authors.forename: W
authors.initials: W
authors.lastname: Magee
authors.forename: H
authors.initials: H
authors.lastname: Masamune
authors.forename: S P
authors.initials: SP
authors.lastname: Kennedy
authors.forename: D R
authors.initials: DR
authors.lastname: Knight
authors.forename: R A
authors.initials: RA
authors.lastname: Buchholz
authors.forename: R J
authors.initials: RJ
authors.lastname: Hill
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control; D010660:Phenylisopropyladenosine / Q000627:therapeutic use*; D011817:Rabbits; D011983:Receptors, Purinergic / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D011983:Receptors, Purinergic; C084956:N(6)-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine; D010660:Phenylisopropyladenosine; D000241:Adenosine