title: Thiamine as a neuroprotective agent after cardiac arrest.
abstract: Reduction of pyruvate dehydrogenase (PDH) activity in the brain is associated with neurological deficits in animals resuscitated from cardiac arrest. Thiamine is an essential co-factor of PDH. The objective of this study was to examine whether administration of thiamine improves outcomes after cardiac arrest in mice. Secondarily, we aimed to characterize the impact of cardiac arrest on PDH activity in mice and humans.
  
  
  
  Animal study: Adult mice were subjected to cardiac arrest whereupon cardiopulmonary resuscitation was performed. Thiamine or vehicle was administered 2min before resuscitation and daily thereafter. Mortality, neurological outcome, and metabolic markers were evaluated. Human study: In a convenience sample of post-cardiac arrest patients, we measured serial PDH activity from peripheral blood mononuclear cells and compared them to healthy controls.
  
  
  
  Animal study: Mice treated with thiamine had increased 10-day survival (48% versus 17%, P<0.01) and improved neurological function when compared to vehicle-treated mice. In addition, thiamine markedly improved histological brain injury compared to vehicle. The beneficial effects of thiamine were accompanied by improved oxygen consumption in mitochondria, restored thiamine pyrophosphate levels, and increased PDH activity in the brain at 10 days. Human study: Post-cardiac arrest patients had lower PDH activity in mononuclear cells than did healthy volunteers (estimated difference: -5.8O.D./min/mg protein, P<0.001).
  
  
  
  The provision of thiamine after cardiac arrest improved neurological outcome and 10-day survival in mice. PDH activity was markedly depressed in post-cardiac arrest patients suggesting that this pathway may represent a therapeutic target.
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kohei
authors.initials: K
authors.lastname: Ikeda
authors.affiliation: Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kida
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Eizo
authors.initials: E
authors.lastname: Marutani
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hirai
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Sakaguchi
authors.affiliation: Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Anaesthesiology, Aarhus University Hospital, Aarhus, Denmark; Research Center for Emergency Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lars W
authors.initials: LW
authors.lastname: Andersen
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Aranya
authors.initials: A
authors.lastname: Bagchi
authors.affiliation: Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Anesthesia Critical Care, Beth Israel Deaconess Medical Center, Boston, MA, USA.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Cocchi
authors.affiliation: Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, MA, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Berg
authors.affiliation: Anesthesia Center for Critical Care Research of the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, USA. Electronic address: fichinose@mgh.harvard.edu.
authors.forename: Fumito
authors.initials: F
authors.lastname: Ichinose
authors.affiliation: Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, MA, USA. Electronic address: mdonnino@bidmc.harvard.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Donnino
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D016887:Cardiopulmonary Resuscitation; D016022:Case-Control Studies; D002540:Cerebral Cortex / Q000187:drug effects; D004195:Disease Models, Animal; D006323:Heart Arrest / Q000188:drug therapy* / Q000401:mortality; D006624:Hippocampus / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D011768:Pyruvate Dehydrogenase Complex / Q000097:blood / Q000378:metabolism*; D011897:Random Allocation; D015996:Survival Rate; D013831:Thiamine / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D015415:Biomarkers; D018696:Neuroprotective Agents; D011768:Pyruvate Dehydrogenase Complex; D013831:Thiamine
keywords: Cardiopulmonary resuscitation; Heart arrest; Mitochondria; Neurological function; Pyruvate dehydrogenase; Thiamine