Abstract 1423: The Cardioprotective Effects of Postconditioning Against Acute Myocardial Infarction are Mediated by Adenosine A2A Receptor Activation
Background: Postconditioning significantly reduces myocardial ischemia/reperfusion injury and infarct size in animals and humans. Pharmacological inhibition studies suggest that endogenous adenosine activates A2A receptors (A2AARs) during postconditioning. This study used A1AAR and A2AAR knock-out (KO) mice to test the hypothesis that pre- and postconditioning are primarily mediated by different sets of adenosine receptors.
Methods: Balloon occluders were placed to occlude the left coronary artery (LCA) in adult male mice (WT, A1AR KO and A2AAR KO). Mice received 40 min of LCA occlusion and 60 min of reperfusion. For preconditioning (Pre-C), 2 cycles of 5 min occlusion and 5 min of reperfusion were applied before the 40 min occlusion. For postconditioning (Post-C), 3 cycles of 5 sec occlusion and 5 sec reperfusion were applied after the 40 min occlusion. Infarct size (IF) as %risk region was determined by TTC+Phthalo blue.
Results: Risk regions (% LV mass) were similar in WT, A1AR & A2AAR KO mice. In WT mice, Pre-C reduced IF from 51±2 to 27±4% (p<0.05), while Post-C reduced IF in WTs to a lesser extent (37±3%, p<0.05 vs WT or WT Pre-C, Fig⇓). In A1AR KOs, Pre-C exerted no cardioprotective effect, while IF reduction with Post-C remained similar to Post-C treated WT mice. Conversely, in A2AAR KOs, IF reduction with Pre-C was similar to that of WTs, but the IF reducing effect of Post-C was abrogated entirely.
Conclusions: 1) Both Pre-C and Post-C confer protection against myocardial IF; Pre-C confers greater protection than Post-C in the in vivo murine model of ischemia-reperfusion; 3) Pre-C is mediated by A1AR activation, while Post-C is mediated by A2AAR activation by endogenous adenosine.