Abstract 13805: Imaging Mass Spectrometry with Focus Microwave Treatment Reveals Heterogeneity in Directional Glucose Fluxes in and Around Ischemic Myocardium
Introduction: Matrix-assisted laser desorption/ionization (MALDI)-imaging-mass spectrometry (MS) combined with a focused microwave irradiation for rapidly fixing tissue metabolism allowed us to quantify and visualize many metabolites within heart tissues in a region-specific manner.
Hypothesis: We assessed the hypothesis that these techniques are applicable to visualization of regional changes in glucose metabolism of murine heart exposed to coronary ischemia.
Methods and Results: Heart-focused microwave irradiation (FMW) was found to be an optimal method to minimize postmortem changes in metabolites induced by ischemia as compared with traditional ways of sacrifice. After 10 min of myocardial ischemia by LAD ligation, quantitative imaging of various metabolites on the same section showed the highest levels of lactate, succinate, NADH in the ischemic core. Distribution of these metabolites was demarcated to that of ATP. Imaging of distinct metabolic fluxes from 13C6-glucose on the same section revealed that the anaerobic glycolytic pathway defined as production of 13C3-lactate is predominant in ischemic regions (white head arrows), while the concomitant conversion of 13C2-glutamate resulting from incorporation through Krebs cycle was predominant in non-ischemic regions (white arrows). Notably, non-ischemic regions adjacent to the ischemic core (white arrows) exhibited greater TCA cycling than those distal from the ischemic core (red arrows). In good agreement with these results, non-ischemic regions adjacent to the ischemic core displayed greater energy charges than those distal from the core (white arrows).
Conclusions: In conclusion, this study is the first to demonstrate usefulness of imaging MS combined with FMW to visualize regional metabolic flux of glucose oxidation, revealing compensatory responses of energy management in the marginal regions between the ischemic core and intact regions in mice.
Author Disclosures: Y. Katsumata: None. Y. Sugiura: None. K. Honda: None. M. Kajimura: None. K. Fukuda: None. M. Sano: None. M. Suematsu: None.
- © 2014 by American Heart Association, Inc.