Introduction/background A1 adenosine receptors (A1AR), have previously been shown to limit injurious infarct development. The purpose of this current study was to determine if delayed activation of A1ARs from 0, 15 or 30 min post-reperfusion can still limit infarct development.
Method Male Sprague-Dawley rats (300±50 g) were mounted on the Langendorff system. A1AR agonist, 2-chloro-N cyclopentyl-2’-methyladenosine (2’-MeCCPA) (0.1 nM-1 M) was administered at the onset of reperfusion as well as 15 and 30 min post-reperfusion (10 nM) in the presence and absence of the A1AR antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 200 nM) as well as in the presence and absence of Wortmannin (100 nM).
Results Administration of 2’-MeCCPA (1 nM-1 M) at reperfusion significantly reduced infarct size to risk ratio. Furthermore, delaying the activation of A1AR to 15 or 30 min post-reperfusion significantly reduced infarct size compared to IR control.
The co-administration of DPCPX (200 nM) with 2’-MeCCPA (10 nM) at the onset of reperfusion significantly attenuated the 2’-MeCCPA mediated infarct. The concomitant administration of 2’-MeCCPA with DPCPX at either 15 or 30 min post-reperfusion also abrogated 2’-MeCCPA induced cardioprotection.
Co-administration of Wortmannin (100 nM) with 2’-MeCCPA (10 nM) at the onset of reperfusion also significantly reduced the 2’-MeCCPA mediated infarct size as well as the co-administration at 15 or 30 min post-reperfusion reversed the cardioprotection.
Conclusion This is the first study to display how 2’-MeCCPA, a highly selective A1AR agonist, when administered at reperfusion, 15 or 30 min post-reperfusion can limit the infarct size development and how the RISK cell signalling pathway is also associated with cardioprotection.
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