Renal ischemia/reperfusion remotely improves myocardial energy metabolism during myocardial ischemia via adenosine receptors in rabbits: Effects of "remote preconditioning"

OBJECTIVES This study examined the changes in myocardial energy metabolism during myocardial ischemia after "remote preconditioning" and investigated the involvement of adenosine receptors in the mechanisms of this effect; BACKGROUND Recent studies have indicated that a brief period of ischemia an d reperfusion (ischemic preconditioning, PC) in a remote organ reduces myoc ardial infarct size (IS) protecting against subsequent sustained myocardial ischemia. However, the mechanisms of "remote PC" remain unclear. We assess ed myocardial energy metabolism during sustained myocardial ischemia and re perfusion after renal PC (RPC), in comparison with that after myocardial PC (MPC) in open-chest rabbits. It has been established that adenosine recept ors 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 fo llowed by 120 min reperfusion. Before the procedure, the MPC group underwen t an additional protocol of 5 min coronary artery occlusion and 20 min repe rfusion, and the RPC group received a 10 min episode of renal artery occlus ion and 20 min reperfusion. In additional experimental groups, 8 sulfopheny ltheophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intrave nously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and R PC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by P-31-NMR spectroscopy. RESULTS RPC and MPC delayed the decreases in ATP levels, preserved pHi duri ng 40-min myocardial ischemia and resulted in better recovery of ATP and PC r 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), RP C (n = 9), SPT (n = 6), MPC + SPT (n = 8) and RPC + SPT (n = 8) groups aver aged 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 area at risk (*p < 0.05 vs. CNT), respectively . CONCLUSIONS PC in a remote organ, similar to MPC, improved myocardial energ y metabolism during ischemia and reperfusion and reduced IS in vivo by an a denosine-dependent mechanism in rabbits. (C) 1999 by the American College o f Cardiology.