title: Changes in energy metabolism due to acute rotenone-induced mitochondrial complex I dysfunction - An in vivo large animal model.
abstract: Metabolic crisis is a clinical condition primarily affecting patients with inherent mitochondrial dysfunction in situations of augmented energy demand. To model this, ten pigs received an infusion of rotenone, a mitochondrial complex I inhibitor, or vehicle. Clinical parameters, blood gases, continuous indirect calorimetry, in vivo muscle oxygen tension, ex vivo mitochondrial respiration and metabolomics were assessed. Rotenone induced a progressive increase in blood lactate which was paralleled by an increase in oxygen tension in venous blood and skeletal muscle. There was an initial decrease in whole body oxygen utilization, and there was a trend towards inhibited mitochondrial respiration in platelets. While levels of succinate were decreased, other intermediates of glycolysis and the TCA cycle were increased. This model may be suited for evaluating pharmaceutical interventions aimed at counteracting metabolic changes due to complex I dysfunction.
authors: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden; NeuroVive Pharmaceutical AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden. Electronic address: michael.karlsson@med.lu.se.
authors: Michael
authors: M
authors: Karlsson
authors: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden; NeuroVive Pharmaceutical AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden. Electronic address: johannes.ehinger@med.lu.se.
authors: Johannes K
authors: JK
authors: Ehinger
authors: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden; NeuroVive Pharmaceutical AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden. Electronic address: sarah.piel@med.lu.se.
authors: Sarah
authors: S
authors: Piel
authors: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden. Electronic address: fredrik.sjovall@med.lu.se.
authors: Fredrik
authors: F
authors: Sjövall
authors: Adlego Biomedical AB, P.O. Box 42, SE-751 03 Uppsala, Sweden. Electronic address: johanna.henriksnas@adlego.se.
authors: Johanna
authors: J
authors: Henriksnäs
authors: Adlego Biomedical AB, P.O. Box 42, SE-751 03 Uppsala, Sweden. Electronic address: urban.hoglund@adlego.se.
authors: Urban
authors: U
authors: Höglund
authors: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden; NeuroVive Pharmaceutical AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden. Electronic address: magnus.hansson@med.lu.se.
authors: Magnus J
authors: MJ
authors: Hansson
authors: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden; NeuroVive Pharmaceutical AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden. Electronic address: eskil.elmer@med.lu.se.
authors: Eskil
authors: E
authors: Elmér
mesh_terms: D000818:Animals; D042967:Electron Transport Complex I / Q000378:metabolism*; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006019:Glycolysis; D007773:Lactates / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D023421:Models, Animal; D010101:Oxygen Consumption / Q000502:physiology; D012402:Rotenone / Q000378:metabolism*; D013552:Swine; D014475:Uncoupling Agents / Q000378:metabolism*
chemical_list: D007773:Lactates; D014475:Uncoupling Agents; D012402:Rotenone; D042967:Electron Transport Complex I
keywords: Animal model; Complex I; Energy metabolism; Metabolic crisis; Mitochondria