Effect of a novel partial adenosine A1 receptor agonist VCP102 in reducing ischemic damage in the mouse heart

Investigations into the use of A1 adenosine receptor (A1AR) agonists in reducing post-ischemic damage to the heart have been of significant interest to cardiovascular research. The present study examined the cardioprotective effects of the partial A1AR agonist, N6-[4-[1,1,3,3-tetramethylisoindolin-2-yloxyl-5amido]ethyl]phenyl]adenosine (VCP102) and the full A1AR agonist, N6-cyclopentyl adenosine (CPA), in murine isolated hearts perfused in Langendorff mode. Following 30-min ischemia, hearts were treated with the A1AR agonists during early reperfusion for 15 min (IR protocol). Significant increases in left ventricular developed pressure (LVDP) and contractility (dP/dtmax) were observed at the final reperfusion values for VCP102 (100 nM)-treated hearts, as compared with the control tissues (P 0.05). Infarct size was also significantly reduced in VCP102- or CPA-treated hearts as compared with control tissues (P 0.05). Significant reductions in cardiac troponin I release and expression of the pro-apoptotic zymogen caspase-3 were observed in both treatment groups (P<0.05). In summary, both A1ARs and A3ARs may play a role in mediating cardioprotection and improving functional recovery in the IR heart with VCP102. Furthermore, treatment with the partial agonist appeared to confer improved functional cardiac protection when compared with CPA. Drug Dev Res 68:529–537, 2007. © 2008 Wiley-Liss, Inc.