All animals are equal but some animals are more equal than others: Plasma lactate and succinate in hemorrhagic shock: A comparison in rodents, swine, non-human primates and injured patients.

Background: Plasma levels of lactate and succinate are predictors of mortality in critically injured patients in military and civilian settings. In relative terms, these metabolic derangements have been recapitulated in rodent, swine and non-human primate models of severe hemorrhage. However, no direct absolute quantitative comparison has been evaluated across these species. Methods: Ultra-high pressure liquid chromatography-mass spectrometry with stable isotope standards was used to determine absolute concentrations of baseline and post-shock levels of lactate and succinate in rats, pigs, macaques, and injured patients. ResultsBaseline levels of lactate and succinate were most comparable to humans in macaques, followed by pigs and rats. Baseline levels of lactate in pigs and baseline and post-shock levels of lactate and succinate in rats were significantly higher than those measured in macaques and humans. Post-shock levels of lactate and succinate in pigs and macaques, respectively, were directly comparable to measurements in critically injured patients. Conclusions: Acknowledging the caveats associated with the variable degrees of shock in the clinical cohort, our data indicates that larger mammals represent a better model than rodents when investigating metabolic derangements secondary to severe hemorrhage. (C) 2017 Lippincott Williams & Wilkins, Inc.

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