Submitted on March 1, 2007
Accepted on May 17, 2007
Ischemic Preconditioning Prevents In Vivo Hyperoxygenation in Postischemic Myocardium with Preservation of Mitochondrial Oxygen Consumption
Xuehai Zhu1, Bin Liu2, Shaotang Zhou1, Yeong R Chen3, Yuanmu Deng3, Jay L Zweier4, and Guanglong He1*
1 Internal Medicine, The Ohio State University, Columbus, Ohio, United States; Davis Heart & Lung Research Institute, Internal Medicine, The Ohio State University, Columbus, Ohio, United States
2 Internal Medicine, The Ohio State University, Columbus, Ohio, United States; Columbus, Ohio, United States; Davis Heart & Lung Research Institute, Internal Medicine, The Ohio State University, Columbus, Ohio, United States
3 Davis Heart & Lung Research Institute, Internal Medicine, The Ohio State University, Columbus, Ohio, United States
4 United States; Davis Heart & Lung Research Institute, Internal Medicine, The Ohio State University, Columbus, Ohio, United States
* To whom correspondence should be addressed. E-mail: Guanglong.He{at}osumc.edu.
Ischemic preconditioning (IPC) strongly protects against ischemia/reperfusion injury, however, its effect on subsequent myocardial oxygenation is unknown. Therefore, we determine in an in vivo mouse model of regional ischemia and reperfusion (I/R) if IPC attenuates postischemic myocardial hyperoxygenation and decreases formation of reactive oxygen/nitrogen species (ROS/RNS), with preservation of mitochondrial function. Five groups of mice: sham, control (I/R), ischemic preconditioning (IPC+I/R, 3 cycles of 5 min coronary occlusion/5 min reperfusion) and IPC+I/R N-nitro-L-arginine methyl ester (L-NAME)-treated, and IPC+I/R eNOS knockout (eNOS-/-) mice. I/R and IPC+I/R mice were subjected to 30 min regional ischemia followed by 60 min reperfusion. Myocardial PO2 and redox state were monitored by electron paramagnetic resonance spectroscopy. In IPC+I/R, but not I/R group, regional blood flow was increased after reperfusion. PO2 upon reperfusion increased significantly above preischemic values in I/R but not in IPC+I/R mice. Tissue redox state was measured from the reduction rate of a spin probe and this rate was 60% higher in IPC than in non-IPC hearts. Activities of NADH dehydrogenase (NADH-DH) and cytochrome c oxidase (CcO) were reduced in I/R mice after 60 min reperfusion but conserved in IPC+I/R mice compared to sham. There were no differences in NADH-DH and CcO expression in I/R and IPC+I/R groups compared to sham. After 60 min reperfusion, strong nitrotyrosine formation was observed in I/R mice but only weak staining in IPC+I/R mice. Thus, IPC markedly attenuates postischemic myocardial hyperoxygenation with less ROS/RNS generation and preservation of mitochondrial O2 metabolism due to conserved NADH-DH and CcO activities.
