Joaquin Lado-Abeal1,2,3, Noelia Martinez-Sánchez4,5, Jose Angel Cocho6, Manuel Martín-Pastor7, Isabel Castro-Piedras8, M Luz Couce-Pico6, Asish K Saha9, Miguel López4. 1. Division of Endocrinology, Department of Internal Medicine, Texas Tech University Health Sciences Center-School of Medicine, Lubbock, TX, USA. josejoaquin.lado-abeal@tmcmed.org. 2. Unidade de Enfermedades Tiroideas e Metabolicas (UETeM), Department of Medicine, University of Santiago de Compostela, Santiago de Compostela, Spain. josejoaquin.lado-abeal@tmcmed.org. 3. Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine Truman Medical Centers, University of Missouri-Kansas City School of Medicine, 2301 Holmes Street, Kansas City, MO, 64108, USA. josejoaquin.lado-abeal@tmcmed.org. 4. NeurObesity Group, Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain. 5. CIBER Fisiopatologia de la Obesidad y Nutricion (CIBERobn), Santiago de Compostela, 15706, Spain. 6. Unidad de Diagnóstico y Tratamiento de las Enfermedades Metabólicas, Complexo Hospitalario Universitario de Santiago de Compostela, Santiago de Compostela, Spain. 7. Unidade de Resonancia Magnética (RIAIDT), Edif, CACTUS, University of Santiago de Compostela, Santiago de Compostela, 15782, Spain. 8. Division of Endocrinology, Department of Internal Medicine, Texas Tech University Health Sciences Center-School of Medicine, Lubbock, TX, USA. 9. Division of Endocrinology, Diabetes and Nutrition, Boston University Medical Center, Boston, MA, USA.
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.
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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