Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemi vi adenosine receptors in rabbits: effects of “remote preconditioning”

Objectives This study examined the changes in myocardial energy metabolism during myocardial ischemi after “remote preconditioning” and investigated the involvement of adenosine receptors in the mechanisms of this effect. Background Recent studies have indicated that brief period of ischemi and reperfusion (ischemic preconditioning, PC) in remote organ reduces myocardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of “remote PC” remain unclear. We assessed myocardial energy metabolism during sustained myocardial ischemi and reperfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine receptors are involved in the mechanisms of MPC. Methods Rabbits that had been anesthetized with halothane were divided into six groups. The control (CNT) group underwent 40-min coronary occlusion followed by 120 min reperfusion. Before the procedure, the MPC group underwent an additional protocol of 5 min coronary artery occlusion and 20 min reperfusion, and the RPC group received 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyltheophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemi (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy. Results RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemi and resulted in better recovery of ATP and PCr during 120 min reperfusion compared with the controls. SPT abolished the improvement in myocardial energy metabolism and the reduction in myocardial IS caused by MPC or RPC. Myocardial IS in the CNT (n = 8), MPC (n = 9), RPC (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups averaged 42.8 ± 3.5%, 18.2 ± 1.8%*, 19.6 ± 1.3%*, 44.9 ± 5.0%, 35.6 ± 2.7% and 34.8 ± 3.6% of the are at risk (*p < 0.05 vs. CNT), respectively. Conclusions PC in remote organ, similar to MPC, improved myocardial energy metabolism during ischemi and reperfusion and reduced IS in vivo by an adenosine-dependent mechanism in rabbits.