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J Proteome Res. 2019 May 3;18(5):2004-2011. doi: 10.1021/acs.jproteome.8b00774. Epub 2019 Apr 1.

Untargeted Metabolomics Differentiates l-Carnitine Treated Septic Shock 1-Year Survivors and Nonsurvivors.

Author information

1
Department of Emergency Medicine, Hennepin County Medical Center, and Department of Emergency Medicine, School of Medicine , University of Minnesota , Minneapolis , Minnesota 55455 , United States.
2
Department of Statistics, College of Literature, Science and Art , University of Michigan and the Informatics Institute University of Florida , Gainesville , Flordia 32611 , United States.
3
Emergency Medicine , University of Mississippi Medical Center , Jackson , Mississippi 39216 , United States.

Abstract

l-Carnitine is a candidate therapeutic for the treatment of septic shock, a condition that carries a ≥40% mortality. Responsiveness to l-carnitine may hinge on unique metabolic profiles that are not evident from the clinical phenotype. To define these profiles, we performed an untargeted metabolomic analysis of serum from 21 male sepsis patients enrolled in a placebo-controlled l-carnitine clinical trial. Although treatment with l-carnitine is known to induce changes in the sepsis metabolome, we found a distinct set of metabolites that differentiated 1-year survivors from nonsurvivors. Following feature alignment, we employed a new and innovative data reduction strategy followed by false discovery correction, and identified 63 metabolites that differentiated carnitine-treated 1-year survivors versus nonsurvivors. Following identification by MS/MS and database search, several metabolite markers of vascular inflammation were determined to be prominently elevated in the carnitine-treated nonsurvivor cohort, including fibrinopeptide A, allysine, and histamine. While preliminary, these results corroborate that metabolic profiles may be useful to differentiate l-carnitine treatment responsiveness. Furthermore, these data show that the metabolic signature of l-carnitine-treated nonsurvivors is associated with a severity of illness (e.g., vascular inflammation) that is not routinely clinically detected.

KEYWORDS:

liquid chromatography−mass spectroscopy; pharmacometabolomics; vascular inflammation

PMID:
30895797
PMCID:
PMC6501183
[Available on 2020-05-03]
DOI:
10.1021/acs.jproteome.8b00774

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