Pharmacological postconditioning of the rabbit heart with non-selective, A1, A2A and A3 adenosine receptor agonists

Objectives We investigated the effects of novel selective and non-selective adenosine receptor agonists (ARs) on cardioprotection. Methods Male rabbits divided into six groups were subjected to 30-min heart ischaemia and 3-h reperfusion: (1) control group, (2) postconditioning (PostC) group, (3) group A: treated with the non-selective agonist (S)-PHPNECA, (4) group B: treated with the A(1) agonist CCPA, (5) group C: treated with the A(2A) agonist VT 7 and (6) group D: treated with the A(3) agonist AR 170. The infarcted (I) and the areas at risk (R) were estimated as %I/R. In additional rabbits of all groups, heart samples were taken for determination of Akt, eNOS and STAT 3 at the 10th reperfusion minute. Key findings (S)-PHPNECA and CCPA reduced the infarct size (17.2 +/- 2.9% and 17.9 +/- 2.0% vs 46.8 +/- 1.9% in control, P < 0.05), conferring a benefit similar to PostC (26.4 +/- 0.3%). Selective A(2A) and A(3) receptor agonists did not reduce the infarct size (39.5 +/- 0.8% and 38.7 +/- 3.5%, P = NS vs control). Akt, eNOS and STAT 3 were significantly activated after non-selective A(1) ARs and PostC. Conclusions Non-selective and A(1) but not A(2A) and A(3) ARs agonists are essential for triggering cardioprotection. The molecular mechanism involves both RISK and the JAK/STAT pathways.