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Filtering by: Creator Stringer, Kathleen Remove constraint Creator: Stringer, Kathleen Keyword biomarker discovery Remove constraint Keyword: biomarker discovery

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  • Data for Early Sepsis-Mediated Metabolic Changes in Blood, Kidney, and Liver Precede Clinical Evidence of Organ Dysfunction

    work
    Creator:
    Stringer, Kathleen
    Description:
    Organ-specific metabolic pathways, including those related to mitochondrial metabolism, could provide insight to mechanisms underlying sepsis-induced organ dysfunction. However, it remains unclear if metabolic changes precede or if they result from organ dysfunction. We determined if blood levels of the mitochondrial metabolites acetylcarnitine and L-carnitine correlate with organ-specific signals of sepsis-induced dysfunction. To achieve this goal, we performed a series of translational analyses of two cohorts of human sepsis and experiments using a murine model of polymicrobial sepsis. We evaluated the association between mitochondrial metabolites and clinical indices of organ function. We found that in the blood of patients with sepsis or septic shock, metabolic indices of dysfunctional mitochondrial beta-oxidation that were correlated with clinical measures of renal and liver dysfunction. The relevance of these findings was corroborated in an experimental model that showed distinct patterns of change in organ metabolism that correlated with the blood acetylcarnitine to L-carnitine ratio. In addition, sepsis-induced changes in organ metabolism were distinct in the liver and kidney highlighting the unique energy economies of each organ. Importantly, these metabolic changes preceded histological evidence of cellular apoptosis. In conclusion, sepsis-induced disruption in blood levels of specific metabolites could serve as more reliable indicators of early organ dysfunction than those we presently use. These early metabolite signals provide mechanistic insights to altered metabolism that may hold the key to timely identification of impending organ dysfunction. This could lead to strategies directed at the prevention of sepsis-induced organ failure.
    Keyword:
    sepsis, organ dysfunction, and biomarker discovery
    Citation to related publication:
    pending
    Discipline:
    Science