%0 Journal Article
%T Transient Acidosis during Early Reperfusion Attenuates Myocardium Ischemia Reperfusion Injury via PI3k-Akt-eNOS Signaling Pathway
%A Xin Qiao
%A Jinjin Xu
%A Qing-Jun Yang
%A Yun Du
%A Shaoqing Lei
%A Zhi-Hong Liu
%A Xinwei Liu
%A Huimin Liu
%J Oxidative Medicine and Cellular Longevity
%D 2013
%I Hindawi Publishing Corporation
%R 10.1155/2013/126083
%X In this paper, we concluded that transient acidosis reperfusion conferred cardioprotection against myocardial ischemia reperfusion injury in isolated rat hearts through activating PI3K-Akt-eNOS pathway. 1. Introduction During myocardial ischemia, tissue pH significantly declines and returns to normal after reperfusion [1]. Recently, studies reported that acidosis (pH < or = 7.0) protected profoundly against cell death during ischemia. However, the quick return from acidotic to normal pH after reperfusion may cause myocytes to lose viability. This worsening of postischemic injury is a ¡°pH paradox¡± mediated by sudden or quick changes of intracellular pH (pHi) [2]. Normalization of pH after reperfusion initiates reactive oxygen species (ROS) formation and onset of the mitochondrial permeability transition pore (MPTP), which finally leads to cell death in cardiomyocytes, while acidosis can prevent mitochondrial permeability transition pore (MPTP) opening [3]. Therefore, prolongation of transient acidosis during early reperfusion may prevent the myocardium ischemia reperfusion injury. Ischemic postconditioning, a novel strategy of cardioprotection consisting of the application of brief cycles of ischemia-reflow at the onset of reperfusion, represents a promising approach to protect the myocardium against ischemia and reperfusion injury [4, 5]. And this protection has been related to the activation of phosphatidylinositol 3-kinase-Akt dependent cytoprotective signaling pathway which is part of the reperfusion injury salvage kinase (RISK) that confers cardioprotection when activated at reperfusion [6, 7]. Additionally, Cohen et al. reported that ischemia postconditioning inhibits reoxygenated myocardium to produce reactive oxygen species and prevents MPTP formation by maintaining acidosis during the first 3 minutes of reperfusion [8]. Therefore, we hypothesized that direct acidotic infusion at the onset of reperfusion (acidosis postconditioning) could mimic ischemic postconditioning and induce the delayed recovery of pH and protect myocardium against ischemia reperfusion injury, and this protective effect may be mediated by PI3k-eNOS signaling pathway. 2. Methods The experimental procedures conformed to the Guide for the Care and Use of Laboratory Animals published by National Institute of Health of the People¡¯s Republic of China and approved by the Institutional Animal Ethics Committee. 2.1. Isolated Perfused Rat Heart Preparation Male Sprague-Dawley rats (450¨C550£¿g) were heparinised and then anaesthetized with urethan (700£¿mg/kg). The hearts were rapidly
%U http://www.hindawi.com/journals/omcl/2013/126083/