title: Persistently Altered Brain Mitochondrial Bioenergetics After Apparently Successful Resuscitation From Cardiac Arrest.
abstract: BACKGROUND
  Although advances in cardiopulmonary resuscitation have improved survival from cardiac arrest (CA), neurologic injury persists and impaired mitochondrial bioenergetics may be critical for targeted neuroresuscitation. The authors sought to determine if excellent cardiopulmonary resuscitation and postresuscitation care and good traditional survival rates result in persistently disordered cerebral mitochondrial bioenergetics in a porcine pediatric model of asphyxia-associated ventricular fibrillation CA.
  
  
  RESULTS
  After 7 minutes of asphyxia, followed by ventricular fibrillation, 5 female 1-month-old swine (4 sham) received blood pressure-targeted care: titration of compression depth to systolic blood pressure of 90 mm Hg and vasopressor administration to a coronary perfusion pressure >20 mm Hg. All animals received protocol-based vasopressor support after return of spontaneous circulation for 4 hours before they were killed. The primary outcome was integrated mitochondrial electron transport system (ETS) function. CA animals displayed significantly decreased maximal, coupled oxidative phosphorylating respiration (OXPHOSCI + CII) in cortex (P<0.02) and hippocampus (P<0.02), as well as decreased phosphorylation and coupling efficiency (cortex, P<0.05; hippocampus, P<0.05). Complex I- and complex II-driven respiration were both significantly decreased after CA (cortex: OXPHOSCI P<0.01, ETSCII P<0.05; hippocampus: OXPHOSCI P<0.03, ETSCII P<0.01). In the hippocampus, there was a significant decrease in maximal uncoupled, nonphosphorylating respiration (ETSCI + CII), as well as a 30% reduction in citrate synthase activity (P<0.04).
  
  
  CONCLUSIONS
  Mitochondria in both the cortex and hippocampus displayed significant alterations in respiratory function after CA despite excellent cardiopulmonary resuscitation and postresuscitation care in asphyxia-associated ventricular fibrillation CA. Analysis of integrated ETS function identifies mitochondrial bioenergetic failure as a target for goal-directed neuroresuscitation after CA. IACUC Protocol: IAC 13-001023.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (T.J.K., R.M.S., M.Y.N., R.W.M., G.B., V.M.N., R.A.B.).
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Kilbaugh
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (T.J.K., R.M.S., M.Y.N., R.W.M., G.B., V.M.N., R.A.B.).
authors.forename: Robert M
authors.initials: RM
authors.lastname: Sutton
authors.affiliation: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden (M.K., M.J.H.).
authors.forename: Michael
authors.initials: M
authors.lastname: Karlsson
authors.affiliation: Mitochondrial Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden (M.K., M.J.H.).
authors.forename: Magnus J
authors.initials: MJ
authors.lastname: Hansson
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (T.J.K., R.M.S., M.Y.N., R.W.M., G.B., V.M.N., R.A.B.).
authors.forename: Maryam Y
authors.initials: MY
authors.lastname: Naim
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (T.J.K., R.M.S., M.Y.N., R.W.M., G.B., V.M.N., R.A.B.).
authors.forename: Ryan W
authors.initials: RW
authors.lastname: Morgan
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (T.J.K., R.M.S., M.Y.N., R.W.M., G.B., V.M.N., R.A.B.).
authors.forename: George
authors.initials: G
authors.lastname: Bratinov
authors.affiliation: Department of Emergency Medicine, The Hospital of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (J.W.L., L.B.B.).
authors.forename: Joshua W
authors.initials: JW
authors.lastname: Lampe
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (T.J.K., R.M.S., M.Y.N., R.W.M., G.B., V.M.N., R.A.B.).
authors.forename: Vinay M
authors.initials: VM
authors.lastname: Nadkarni
authors.affiliation: Department of Emergency Medicine, The Hospital of the University of Pennsylvania, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (J.W.L., L.B.B.).
authors.forename: Lance B
authors.initials: LB
authors.lastname: Becker
authors.affiliation: Department of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA (S.S.M.).
authors.forename: Susan S
authors.initials: SS
authors.lastname: Margulies
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA (T.J.K., R.M.S., M.Y.N., R.W.M., G.B., V.M.N., R.A.B.).
authors.forename: Robert A
authors.initials: RA
authors.lastname: Berg
mesh_terms: D000818:Animals; D001237:Asphyxia / Q000150:complications; D019069:Cell Respiration; D002540:Cerebral Cortex / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D045222:Electron Transport Chain Complex Proteins / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006323:Heart Arrest / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D006439:Hemodynamics; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism*; D010766:Phosphorylation; D012151:Resuscitation; D013552:Swine; D013997:Time Factors; D014693:Ventricular Fibrillation / Q000150:complications
chemical_list: D045222:Electron Transport Chain Complex Proteins
keywords: acute brain injury; brain; cardiac arrest; electron transport system; mitochondria; neuroprotection