Nitric oxide (NO) has been shown in vitro to play an important role in the regulation of oxygen consumption on the mitochondrial respiratory chain. Our preliminary data demonstrated that oxygen consumption in the postischemic in vivo mouse heart was suppressed and the suppression showed a reversible and an irreversible phase. Whether NO can regulate mitochondrial respiration in vivo and whether this regulation plays a protective role in the postischemic myocardium still remains an important unresolved question. In order to determine the in vivo regulatory role of NO on mitochondrial respiration, real-time myocardial tissue oxygen consumption and tissue injury need to be assessed. However, until recently it was impossible to measure these critical parameters in the beating heart due to the lack of in vivo techniques. Recently, electron paramagnetic resonance (EPR) oximetry and imaging techniques have been developed using a novel surface coil resonator (SCR) with automatic tuning control (ATC), automatic coupling control (ACC), and cardiac gating capability. By employing these techniques, we are able to perform oximetry and imaging measurements on the in vivo mouse heart to determine: (1) real-time variations in tissue oxygen tension and blood flow for the assessment of oxygen consumption during and after regional ischemia and reperfusiion; (2) regulation of oxygen consumption in the postischemic myocardium by eNOS-derived NO and its derivative peroxynitrite; (3) real-time alterations in postischemic myocardial injury and thereby determine the protective role of NO via the suppression of oxygen consumption. Overall, we will utilize the unique capabilities of in vivo EPR spectroscopy and imaging to provide direct and noninvasive measurement and imaging of myocardial tissue pO2, tissue oxygen consumption, redox status, and viability. Critical information will be obtained regarding the regulatory role of endothelium-derived NO on myocardial oxygen consumption, redox alterations, and postichemic myocardial injury and protection in cardiac physiology and disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL081630-04
Application #
7479877
Study Section
Myocardial Ischemia and Metabolism Study Section (MIM)
Program Officer
Evans, Frank
Project Start
2005-09-01
Project End
2010-08-31
Budget Start
2008-09-01
Budget End
2010-08-31
Support Year
4
Fiscal Year
2008
Total Cost
$318,945
Indirect Cost
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Li, Yuanjing; Cai, Ming; Sun, Qinghua et al. (2013) Hyperoxia and transforming growth factor ?1 signaling in the post-ischemic mouse heart. Life Sci 92:547-54
Li, Yuanjing; Cai, Ming; Xu, Yi et al. (2011) Late phase ischemic preconditioning preserves mitochondrial oxygen metabolism and attenuates post-ischemic myocardial tissue hyperoxygenation. Life Sci 88:57-64
Cai, Ming; Li, Yuanjing; Xu, Yi et al. (2011) Endothelial NOS activity and myocardial oxygen metabolism define the salvageable ischemic time window for ischemic postconditioning. Am J Physiol Heart Circ Physiol 300:H1069-77
Liu, Bin; Zhu, Xuehai; Chen, Chwen-Lih et al. (2010) Opening of the mitoKATP channel and decoupling of mitochondrial complex II and III contribute to the suppression of myocardial reperfusion hyperoxygenation. Mol Cell Biochem 337:25-38
Liu, Bin; Tewari, Arun K; Zhang, Liwen et al. (2009) Proteomic analysis of protein tyrosine nitration after ischemia reperfusion injury: mitochondria as the major target. Biochim Biophys Acta 1794:476-85
Xu, Yi; Liu, Bin; Zweier, Jay L et al. (2008) Formation of hydrogen peroxide and reduction of peroxynitrite via dismutation of superoxide at reperfusion enhances myocardial blood flow and oxygen consumption in postischemic mouse heart. J Pharmacol Exp Ther 327:402-10
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He, Guanglong; Dumitrescu, Cristian; Petryakov, Sergey et al. (2007) Transverse oriented electric field re-entrant resonator (TERR) with automatic tuning and coupling control for EPR spectroscopy and imaging of the beating heart. J Magn Reson 187:57-65

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