title: Metabolic spectroscopy of inflammation in a bleomycin-induced lung injury model using hyperpolarized 1-(13) C pyruvate.
abstract: Metabolic activity in the lung is known to change in response to external insults, inflammation, and cancer. We report measurements of metabolism in the isolated, perfused rat lung of healthy controls and in diseased lungs undergoing acute inflammation using hyperpolarized 1-(13) C-labeled pyruvate. The overall apparent activity of lactate dehydrogenase is shown to increase significantly (on average by a factor of 3.3) at the 7 day acute stage and to revert substantially to baseline at 21 days, while other markers indicating monocarboxylate uptake and transamination rate are unchanged. Elevated lung lactate signal levels correlate well with phosphodiester levels as determined with (31) P spectroscopy and with the presence of neutrophils as determined by histology, consistent with a relationship between intracellular lactate pool labeling and the density and type of inflammatory cells present. We discuss several alternate hypotheses, and conclude that the most probable source of the observed signal increase is direct uptake and metabolism of pyruvate by inflammatory cells and primarily neutrophils. This signal is seen in high contrast to the low baseline activity of the lung.
authors.affiliation: Department of Radiology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Hoora
authors.initials: H
authors.lastname: Shaghaghi
authors.forename: Stephen
authors.initials: S
authors.lastname: Kadlecek
authors.forename: Charuhas
authors.initials: C
authors.lastname: Deshpande
authors.forename: Sarmad
authors.initials: S
authors.lastname: Siddiqui
authors.forename: Daniel
authors.initials: D
authors.lastname: Martinez
authors.forename: Mehrdad
authors.initials: M
authors.lastname: Pourfathi
authors.forename: Hooman
authors.initials: H
authors.lastname: Hamedani
authors.forename: Masaru
authors.initials: M
authors.lastname: Ishii
authors.forename: Harrilla
authors.initials: H
authors.lastname: Profka
authors.forename: Rahim
authors.initials: R
authors.lastname: Rizi
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001761:Bleomycin; D002247:Carbon Isotopes; D004195:Disease Models, Animal; D007249:Inflammation / Q000378:metabolism* / Q000473:pathology*; D019344:Lactic Acid / Q000378:metabolism; D055370:Lung Injury / Q000378:metabolism* / Q000473:pathology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D019289:Pyruvic Acid / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D001761:Bleomycin; D019344:Lactic Acid; D019289:Pyruvic Acid
keywords: hyperpolarized; inflammation; lung; macrophage; metabolism; neutrophil