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This study was conducted to investigate the relative contributions of inflammation and hypoxia to the lung's metabolic shift to glycolysis in an experimental animal model of ARDS using hyperpolarized (HP) <jats:sup>13<\/jats:sup>C MRI. Fifty\u2010three intubated and mechanically ventilated male rats were imaged using HP <jats:sup>13<\/jats:sup>C MRI before, and 1, 2.5 and 4 hours after saline (sham) or hydrochloric acid (HCl; 0.5 ml\/kg) instillation in the trachea, followed by protective and nonprotective mechanical ventilation (HCl\u2010PEEP and HCl\u2010ZEEP) or the start of moderate or severe hypoxia (Hyp90 and Hyp75 groups). Pulmonary and cardiac HP lactate\u2010to\u2010pyruvate ratios were compared among groups for different time points. Postmortem histology and immunofluorescence were used to assess lung injury severity and quantify the expression of innate inflammatory markers and local tissue hypoxia. HP pulmonary lactate\u2010to\u2010pyruvate ratio progressively increased in rats with lung injury and moderate hypoxia (HCl\u2010ZEEP), with no significant change in pulmonary lactate\u2010to\u2010pyruvate ratio in noninjured but moderately hypoxic rats (Hyp90). Pulmonary lactate\u2010to\u2010pyruvate ratio was elevated in otherwise healthy lung tissue only in severe systemic hypoxia (Hyp75 group). ex vivo histological and immunopathological assessment further confirmed the link between elevated glycolysis and the recruitment into and presence of activated neutrophils in injured lungs. HP lactate\u2010to\u2010pyruvate ratio is elevated in injured lungs predominantly as a result of increased glycolysis in activated inflammatory cells, but can also increase due to severe inflammation\u2010induced hypoxia.<\/jats:p>","DOI":"10.1002\/nbm.4380","type":"journal-article","created":{"date-parts":[[2020,7,18]],"date-time":"2020-07-18T05:31:00Z","timestamp":1595050260000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Pulmonary pyruvate metabolism as an index of inflammation and injury in a rat model of acute respiratory distress syndrome"],"prefix":"10.1002","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9145-6438","authenticated-orcid":false,"given":"Mehrdad","family":"Pourfathi","sequence":"first","affiliation":[{"name":"Department of Radiology University of Pennsylvania  Philadelphia Pennsylvania 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