Abstract
Introduction
Energy deficiency is a cause for myocardial dysfunction during septic shock. In rodents, septic shock decreases the oxidation of long-chain fatty acids and glucose in the myocardium causing energy deficiency. However, the effect of septic shock on myocardial energy metabolites in large animals and human is unknown.
Objectives
Investigate the effects of septic shock on myocardial energy metabolites in domestic pigs.
Methods
Seventeen female pigs divided into control and lipopolysaccharide (LPS)-induced septic shock groups. Myocardial metabolites were analyzed ex vivo by 1H nuclear magnetic resonance spectroscopy and liquid chromatography-tandem mass spectrometry. Gene and protein expression analysis were analyzed by real-time PCR and western blot.
Results
Septic shock was associated with an increase in myocardial levels of short- and medium-chain acylcarnitines, lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression. COX-2 and prostaglandin E4 receptor gene expression also increased in the septic myocardium, although the only elevated eicosanoid in the septic animals was thromboxane B2. Myocardial levels of niacin, taurine, glutamate, glutamine, and glutathione were higher, and hypoxanthine levels lower in septic pigs than controls.
Conclusions
In pigs, septic shock induced by LPS caused myocardial changes directed to decrease the oxidation of medium- and short-chain fatty acid without an effect on long-chain fatty acid oxidation. The increase in myocardial levels of lactate, alanine, and pyruvate dehydrogenase kinase 4 gene expression suggest that septic shock decreases pyruvate dehydrogenase complex activity and glucose oxidation. Homeostasis of niacin, taurine, glutamate, glutamine, glutathione, hypoxanthine and thromboxane B2 is also affected in the septic myocardium.
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Data availability statement
The metabolomics and metadata reported in this paper are available via Mendeley, https://data.mendeley.com/datasets/nddgfyft7d/1
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Funding
This work was supported by CH Foundation (J LA), Texas Tech University Health Sciences Center-School of Medicine Clinical and Basic Science Cardiology Seed Grant Program (J LA), European Community’s Seventh Framework Programme (FP7/2007–2013) under Grant agreement No. 281854—the ObERStress project (ML); Xunta de Galicia (M.: 2015-CP079); CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII.–
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JLA conceived, designed, obtained funds and coordinated the project. He performed the animal studies and wrote the manuscript. NMS performed the protein and enzyme analysis and contributed to the writing and editing the manuscript. JAC and MLCP performed the acylcarnitine study, obtained research funds and contributed to writing and editing the manuscript. MMP performed the nuclear magnetic resonance spectroscopy based metabolite profile, obtained research funds and contributed to writing and editing the manuscript. ICP performed the animal studies and the gene expression analysis. AKS performed de malonyl-CoA assays. ML performed the protein and enzyme assays, edited the manuscript and obtained research funds to support the project. All authors read and approved the manuscript.
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Lado-Abeal, J., Martinez-Sánchez, N., Cocho, J.A. et al. Lipopolysaccharide (LPS)-induced septic shock causes profound changes in myocardial energy metabolites in pigs. Metabolomics 14, 131 (2018). https://doi.org/10.1007/s11306-018-1433-x
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DOI: https://doi.org/10.1007/s11306-018-1433-x