1005-80 Evidence That A3-Receptor Activation Contributes to Preconditioning-induced Cardioprotection in Ischemic Cardiac Myocytes

Abstract

Ischemic preconditioning (PC) reduces post-ischemic myocardial injury by an adenosine-mediated mechanism. This study evaluated the adenosine receptors involved in protecting ischemic cardiac myocytes. Ischemic injury was simulated by exposure of the myocytes (paced at 1 Hz) to ischemic buffer containing (mM) 2’-deoxyglucose (20), NaCN (1), Na-lactate (20), K + (10) at pH o 6.6 (37°C). Changes of myocyte length were monitored with an opticalvideo edge recording system, and hypercontracture was used as the index of irreversible cell injury (cell death). PC (2 min ischemia followed by 15 min reperfusion) significantly reduced cell injury resulting from the subsequentextended ischemia (10 min) and reperfusion (15 min), as indicated bya reduction in cell death from 67 ± 6% (cells = 110, control) to 29 ± 5% (cells = 101, with PC, p < 0.001). PC-induced cardioprotection was only partially blocked by the maximally effective dose of the adenosine A, -receptor antagonist DPCPX (100 nM) Icell death = 43 ± 3%, cells = 88, P < 0.05 vs control) but completely blocked by either the combination of DPCPX (100 nM) with the adenosine A3-receptor antagonist BW A1433 (1 /LM) (cell death = 64 ± 4%; cells = 82; P = NS vs control). or the non-selective adenosine receptor antagonist, 8-SPT (100 /LM) (cell death = 59 ± 5%; cells = 86; P = NS vs control). as shown in the Figure. Conclusion: PC-induced cardioprotection is mediated in part through the activation of adenosine A3-receptors.