PMID- 21050865 OWN - NLM STAT- MEDLINE DCOM- 20110121 LR - 20211020 IS - 1879-0631 (Electronic) IS - 0024-3205 (Print) IS - 0024-3205 (Linking) VI - 88 IP - 1-2 DP - 2011 Jan 3 TI - Late phase ischemic preconditioning preserves mitochondrial oxygen metabolism and attenuates post-ischemic myocardial tissue hyperoxygenation. PG - 57-64 LID - 10.1016/j.lfs.2010.10.022 [doi] AB - AIMS: Late phase ischemic preconditioning (LPC) protects the heart against ischemia-reperfusion (I/R) injury. However, its effect on myocardial tissue oxygenation and related mechanism(s) is unknown. The aim of the current study is to determine whether LPC attenuates post-ischemic myocardial tissue hyperoxygenation through preserving mitochondrial oxygen metabolism. MAIN METHODS: C57BL/6 mice were subjected to 30 min coronary ligation followed by 60 min or 24 h reperfusion with or without LPC (3 cycles of 5 min I/5 min R): Sham, LPC, I/R, and LPC+I/R group. Myocardial tissue Po(2) and redox status were measured with electron paramagnetic resonance (EPR) spectroscopy. KEY FINDINGS: Upon reperfusion, tissue Po(2) rose significantly above the pre-ischemic level in the I/R mice (23.1 +/- 2.2 vs. 12.6 +/- 1.3 mmHg, p<0.01). This hyperoxygenation was attenuated by LPC in the LPC+I/R mice (11.9 +/- 2.0 mmHg, p<0.01). Activities of NADH dehydrogenase (NADH-DH), succinate-cytochrome c reductase (SCR) and cytochrome c oxidase (CcO) were preserved or increased in the LPC group, significantly reduced in the I/R group, and conserved in the LPC+I/R group. Manganese superoxide dismutase (Mn-SOD) protein expression was increased by LPC in the LPC and LPC+I/R mice compared to that in the Sham control (1.24 +/- 0.01 and 1.23 +/- 0.01, p<0.05). Tissue redox status was shifted to the oxidizing state with I/R (0.0268 +/- 0.0016/min) and was corrected by LPC in the LPC+I/R mice (0.0379 +/- 0.0023/min). Finally, LPC reduced the infarct size in the LPC+I/R mice (10.5 +/- 0.4% vs. 33.3 +/- 0.6%, p<0.05). SIGNIFICANCE: Thus, LPC preserved mitochondrial oxygen metabolism, attenuated post-ischemic myocardial tissue hyperoxygenation, and reduced I/R injury. CI - Copyright (c) 2010 Elsevier Inc. All rights reserved. FAU - Li, Yuanjing AU - Li Y AD - The Center for Biomedical EPR Spectroscopy and Imaging, Davis Heart and Lung Research Institute and Division of Cardiovascular Medicine, Department of Internal Medicine, The Ohio State University College of Medicine, Columbus, OH 43210, USA. FAU - Cai, Ming AU - Cai M FAU - Xu, Yi AU - Xu Y FAU - Swartz, Harold M AU - Swartz HM FAU - He, Guanglong AU - He G LA - eng GR - R01 HL081630-04/HL/NHLBI NIH HHS/United States GR - HL081630/HL/NHLBI NIH HHS/United States GR - R01 HL081630/HL/NHLBI NIH HHS/United States GR - R01 HL081630-02/HL/NHLBI NIH HHS/United States GR - R01 HL081630-03/HL/NHLBI NIH HHS/United States GR - R01 HL081630-04S1/HL/NHLBI NIH HHS/United States GR - P01 EB002180/EB/NIBIB NIH HHS/United States GR - R01 HL081630-01/HL/NHLBI NIH HHS/United States GR - P01EB2180/EB/NIBIB NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20101102 PL - Netherlands TA - Life Sci JT - Life sciences JID - 0375521 RN - EC 1.- (Succinate Cytochrome c Oxidoreductase) RN - EC 1.6.99.3 (NADH Dehydrogenase) RN - EC 1.9.3.1 (Electron Transport Complex IV) RN - S88TT14065 (Oxygen) SB - IM MH - Animals MH - Blotting, Western MH - Electron Spin Resonance Spectroscopy MH - Electron Transport Complex IV/metabolism MH - *Ischemic Preconditioning, Myocardial MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Mitochondria, Heart/*metabolism/physiology MH - Myocardial Infarction/enzymology/metabolism/physiopathology MH - Myocardial Reperfusion Injury/metabolism/physiopathology/*prevention & control MH - Myocardium/enzymology/metabolism MH - NADH Dehydrogenase/metabolism MH - Oxidation-Reduction MH - Oxygen/metabolism MH - Regional Blood Flow/physiology MH - Succinate Cytochrome c Oxidoreductase/metabolism PMC - PMC3026613 MID - NIHMS250506 EDAT- 2010/11/06 06:00 MHDA- 2011/01/22 06:00 PMCR- 2012/01/03 CRDT- 2010/11/06 06:00 PHST- 2010/07/27 00:00 [received] PHST- 2010/10/01 00:00 [revised] PHST- 2010/10/19 00:00 [accepted] PHST- 2010/11/06 06:00 [entrez] PHST- 2010/11/06 06:00 [pubmed] PHST- 2011/01/22 06:00 [medline] PHST- 2012/01/03 00:00 [pmc-release] AID - S0024-3205(10)00483-2 [pii] AID - 10.1016/j.lfs.2010.10.022 [doi] PST - ppublish SO - Life Sci. 2011 Jan 3;88(1-2):57-64. doi: 10.1016/j.lfs.2010.10.022. Epub 2010 Nov 2.