Selective adenosine A(3) receptor stimulation reduces ischemic myocardial injury in the rabbit heart

Objective: The aim of this study was to determine whether selective activation of the adenosine A(3) 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 (ZA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A(3)-selective agonist, IB-MECA (A(3) K-i: 2 nM; A(1), K-i: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A(1)-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 A(1)-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A(1) vs. A(3)) concentration of BWA1433 (5 mu M) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR). Conclusions: These data clearly demonstrate that selective A(3) receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A(3)-dependent cardioprotection is similar to that provided by A(1) receptor stimulation or ischemic preconditioning.