Takaoka A, Nakae I, Mitsunami K, Yabe T, Morikawa S, Inubushi T, Kinoshita M
First Department of Internal Medicine, Shiga University of Medical Science, Seta, Otsu, Japan.
J Am Coll Cardiol. 1999 Feb;33(2):556-64. doi: 10.1016/s0735-1097(98)00559-2.
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.
Recent studies have indicated that a brief period of ischemia and reperfusion (ischemic preconditioning, PC) in a 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 ischemia 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.
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 a 10 min episode of renal artery occlusion and 20 min reperfusion. In additional experimental groups, 8 sulfophenyl-theophylline (SPT, 10 mg/kg), an adenosine receptor inhibitor, was intravenously injected before the 40 min myocardial ischemia (SPT, MPC + SPT and RPC + SPT groups, respectively). Myocardial levels of phosphocreatine (PCr), ATP and intracellular pH (pHi) were measured by 31P-NMR spectroscopy.
RPC and MPC delayed the decreases in ATP levels, preserved pHi during 40-min myocardial ischemia 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 area at risk (*p < 0.05 vs. CNT), respectively.
PC in a remote organ, similar to MPC, improved myocardial energy metabolism during ischemia and reperfusion and reduced IS in vivo by an adenosine-dependent mechanism in rabbits.
本研究检测“远程预处理”后心肌缺血期间心肌能量代谢的变化，并探讨腺苷受体在该效应机制中的作用。
近期研究表明，远处器官短暂的缺血再灌注（缺血预处理，PC）可减小心肌梗死面积（IS），保护心脏免受随后持续心肌缺血的损伤。然而，“远程PC”的机制尚不清楚。我们评估了开胸兔肾PC（RPC）后持续心肌缺血和再灌注期间的心肌能量代谢，并与心肌PC（MPC）后的情况进行比较。已知腺苷受体参与MPC的机制。
用氟烷麻醉的兔子分为六组。对照组（CNT）进行40分钟冠状动脉闭塞，随后120分钟再灌注。在手术前，MPC组进行额外的5分钟冠状动脉闭塞和20分钟再灌注方案，RPC组接受10分钟肾动脉闭塞和20分钟再灌注。在其他实验组中，在40分钟心肌缺血前静脉注射8-磺苯基-茶碱（SPT，10mg/kg）（分别为SPT组、MPC + SPT组和RPC + SPT组）。通过31P-NMR光谱法测量心肌磷酸肌酸（PCr）、ATP水平和细胞内pH（pHi）。
与对照组相比，RPC和MPC延缓了ATP水平的下降，在40分钟心肌缺血期间维持了pHi，并在120分钟再灌注期间使ATP和PCr得到更好的恢复。SPT消除了MPC或RPC引起的心肌能量代谢改善和心肌IS减小。CNT组（n = 8）、MPC组（n = 9）、RPC组（n = 9）、SPT组（n = 6）、MPC + SPT组（n = 8）和RPC + SPT组（n = 8）的心肌IS分别平均为危险区域面积的42.8±3.5%、18.2±1.8%、19.6±1.3%、44.9±5.0%、35.6±2.7%和34.8±3.6%（*与CNT组相比，p < 0.05）。
与MPC相似，远处器官的PC通过腺苷依赖机制改善了缺血和再灌注期间的心肌能量代谢，并减小了兔体内的IS。
