| Intermittent Hypobaric Hypoxia Improves Post-ischemic Recovery of Myocardial Contractile Function via Redox Signaling during Early Reperfusion. | |
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MedLine Citation:
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PMID: 21821784 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Intermittent hypobaric hypoxia (IHH) protects hearts against ischemia/reperfusion (I/R) injury, but the underlying mechanisms are far from clear. Reactive oxygen species (ROS) are paradoxically regarded as a major cause of myocardial I/R injury and a trigger of cardioprotection. In the present study, we investigated whether the ROS generated during early reperfusion contribute to the IHH-induced cardioprotection. Using isolated perfused rat hearts, we found that IHH significantly improved the post-ischemic recovery of left ventricular (LV) contractile function with a concurrent reduction of lactate dehydrogenase (LDH) release and myocardial infarct size (20.5 ± 5.3% in IHH vs. 42.1 ± 3.8% in normoxic control, P < 0.01) after I/R. Meanwhile, IHH enhanced the production of protein carbonyls and malondialdehyde, respective products of protein oxidation and lipid peroxidation, in reperfused myocardium and the ROS generation in reperfused cardiomyocytes. Such effects were blocked by a mitochondrial ATP-sensitive potassium channel inhibitor 5-hydroxydecanoate. Moreover, the IHH-improved post-ischemic LV performance and the enhanced phosphorylation of protein kinase B (Akt/PKB), protein kinase Cε (PKCε) and glycogen synthase kinase-3β, as well as the translocation of PKCε were not affected by applying hydrogen peroxide (20 μmol/L) during early reperfusion but abolished by ROS scavengers, N-(2-mercaptopropionyl) glycine (MPG) and manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin. Furthermore, the IHH-reduced LDH release and infarct size were reversed by MPG. Consistently, inhibiting Akt with wortmannin and PKCε with εV1-2 abrogated the IHH-improved post-ischemic LV performance. These findings suggest that the IHH-induced cardioprotection depends on the elevated ROS production during early reperfusion. |
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Authors:
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Zhi-Hua Wang; Yi-Xiong Chen; Cai-Mei Zhang; Lan Wu; Zhuo Yu; Xiao-Long Cai; Yi Guan; Zhao-Nian Zhou; Huang-Tian Yang |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-8-5 |
Journal Detail:
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Title: American journal of physiology. Heart and circulatory physiology Volume: - ISSN: 1522-1539 ISO Abbreviation: - Publication Date: 2011 Aug |
Date Detail:
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Created Date: 2011-8-8 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 100901228 Medline TA: Am J Physiol Heart Circ Physiol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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