title: Visualization of in vivo metabolic flows reveals accelerated utilization of glucose and lactate in penumbra of ischemic heart.
abstract: Acute ischemia produces dynamic changes in labile metabolites. To capture snapshots of such acute metabolic changes, we utilized focused microwave treatment to fix metabolic flow in vivo in hearts of mice 10 min after ligation of the left anterior descending artery. The left ventricle was subdivided into short-axis serial slices and the metabolites were analyzed by capillary electrophoresis mass spectrometry and matrix-assisted laser desorption/ionization imaging mass spectrometry. These techniques allowed us to determine the fate of exogenously administered (13)C6-glucose and (13)C3-lactate. The penumbra regions, which are adjacent to the ischemic core, exhibited the greatest adenine nucleotide energy charge and an adenosine overflow extending from the ischemic core, which can cause ischemic hyperemia. Imaging analysis of metabolic pathway flows revealed that the penumbra executes accelerated glucose oxidation, with remaining lactate utilization for tricarboxylic acid cycle for energy compensation, suggesting unexpected metabolic interplays of the penumbra with the ischemic core and normoxic regions.
authors: Department of Biochemistry, Keio University School of Medicine, Tokyo, 160-8582, Japan.|Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Tokyo, 102-0076, Japan.
authors: Yuki
authors: Y
authors: Sugiura
authors: Department of Cardiology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors: Yoshinori
authors: Y
authors: Katsumata
authors: Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency, Tokyo, 102-0076, Japan.|Department of Cardiology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors: Motoaki
authors: M
authors: Sano
authors: Department of Biochemistry, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors: Kurara
authors: K
authors: Honda
authors: Department of Biochemistry, Keio University School of Medicine, Tokyo, 160-8582, Japan.|Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology, Suematsu Gas Biology Project, Tokyo, 102-0076, Japan.
authors: Mayumi
authors: M
authors: Kajimura
authors: Department of Cardiology, Keio University School of Medicine, Tokyo, 160-8582, Japan.
authors: Keiichi
authors: K
authors: Fukuda
authors: Department of Biochemistry, Keio University School of Medicine, Tokyo, 160-8582, Japan.|Exploratory Research for Advanced Technology (ERATO), Japan Science and Technology, Suematsu Gas Biology Project, Tokyo, 102-0076, Japan.
authors: Makoto
authors: M
authors: Suematsu
mesh_terms: D000818:Animals; D002247:Carbon Isotopes; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D008810:Mice, Inbred C57BL; D008872:Microwaves; D017202:Myocardial Ischemia / Q000378:metabolism*
chemical_list: D002247:Carbon Isotopes; D019344:Lactic Acid; D018698:Glutamic Acid; D005947:Glucose