title: Characterization of mitochondrial injury after cardiac arrest (COMICA).
abstract: Mitochondrial injury post-cardiac arrest has been described in pre-clinical settings but the extent to which this injury occurs in humans remains largely unknown. We hypothesized that increased levels of mitochondrial biomarkers would be associated with mortality and neurological morbidity in post-cardiac arrest subjects.
  
  
  
  We performed a prospective multicenter study of post-cardiac arrest subjects. Inclusion criteria were comatose adults who suffered an out-of-hospital cardiac arrest. Mitochondrial biomarkers were measured at 0, 12, 24, 36 and 48h after return of spontaneous circulation as well as in healthy controls.
  
  
  
  Out of 111 subjects enrolled, 102 had evaluable samples at 0h. Cardiac arrest subjects had higher baseline cytochrome c levels compared to controls (2.18ng/mL [0.74, 7.74] vs. 0.16ng/mL [0.03, 0.91], p<0.001), and subjects who died had higher 0h cytochrome c levels compared to survivors (3.66ng/mL [1.40, 14.9] vs. 1.27ng/mL [0.16, 2.37], p<0.001). There were significantly higher Ribonuclease P (RNaseP) (3.3 [1.2, 5.7] vs. 1.2 [0.8, 1.2], p<0.001) and Beta-2microglobulin (B2M) (12.0 [1.0, 22.9], vs. 0.6 [0.6, 1.3], p<0.001) levels in cardiac arrest subjects at baseline compared to the control subjects. There were no differences between survivors and non-survivors for mitochondrial DNA, nuclear DNA, or cell free DNA.
  
  
  
  Cytochrome c was increased in post- cardiac arrest subjects compared to controls, and in post-cardiac arrest non-survivors compared to survivors. Nuclear DNA and cell free DNA was increased in plasma of post-cardiac arrest subjects. There were no differences in mitochondrial DNA, nuclear DNA, or cell free DNA between survivors and non-survivors. Mitochondrial injury markers showed mixed results in the post-cardiac arrest period. Future research needs to investigate these differences.
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Emergency Medicine, Boston, MA, United States; Beth Israel Deaconess Medical Center, Department of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Boston, MA, United States. Electronic address: mdonnino@bidmc.harvard.edu.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Donnino
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Emergency Medicine, Boston, MA, United States.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Emergency Medicine, Boston, MA, United States; Aarhus University Hospital, Research Center for Emergency Medicine, Aarhus, Denmark; Aarhus University Hospital, Department of Anesthesiology,, Aarhus, Denmark.
authors.forename: Lars W
authors.initials: LW
authors.lastname: Andersen
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors.forename: Jon C
authors.initials: JC
authors.lastname: Rittenberger
authors.affiliation: University of Pennsylvania, Center for Resuscitation Science, Philadelphia, PA, United States.
authors.forename: Benjamin S
authors.initials: BS
authors.lastname: Abella
authors.affiliation: Thomas Jefferson University Hospital, Department of Emergency Medicine, Philadelphia, PA, United States.
authors.forename: David F
authors.initials: DF
authors.lastname: Gaieski
authors.affiliation: Virginia Commonwealth University, Department of Emergency Medicine, Richmond, VA, United States.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Ornato
authors.affiliation: Rosalind Franklin University of Medicine and Science, Resuscitation Institute and Division of Critical Care Medicine, North Chicago, IL, United States.
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Gazmuri
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Emergency Medicine, Boston, MA, United States.
authors.forename: Anne V
authors.initials: AV
authors.lastname: Grossestreuer
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Emergency Medicine, Boston, MA, United States; Beth Israel Deaconess Medical Center, Department of Anesthesia Critical Care, Division of Critical Care, Boston, MA, United States.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Cocchi
authors.affiliation: Virginia Commonwealth University, Department of Internal Medicine, Richmond, VA, United States.
authors.forename: Antonio
authors.initials: A
authors.lastname: Abbate
authors.affiliation: Beth Israel Deaconess Medical Center, Department of Emergency Medicine, Boston, MA, United States.
authors.forename: Amy
authors.initials: A
authors.lastname: Uber
authors.affiliation: Virginia Commonwealth University, Department of Internal Medicine, Richmond, VA, United States.
authors.forename: John
authors.initials: J
authors.lastname: Clore
authors.affiliation: Virginia Commonwealth University, Department of Internal Medicine and Emergency Medicine, Richmond, VA, United States.
authors.forename: Mary Anne
authors.initials: MA
authors.lastname: Peberdy
authors.affiliation: University of Pittsburgh School of Medicine, Pittsburgh, United States.
authors.forename: Clifton W
authors.initials: CW
authors.lastname: Callaway
mesh_terms: D000368:Aged; D016887:Cardiopulmonary Resuscitation / Q000379:methods; D003128:Coma / Q000175:diagnosis / Q000209:etiology / Q000378:metabolism; D045304:Cytochromes c / Q000097:blood*; D004272:DNA, Mitochondrial / Q000097:blood*; D005260:Female; D006323:Heart Arrest / Q000150:complications / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009422:Nervous System Diseases / Q000209:etiology / Q000378:metabolism; D043262:Ribonuclease P / Q000097:blood; D013223:Statistics as Topic; D016019:Survival Analysis; D017741:Survivors
chemical_list: D004272:DNA, Mitochondrial; D045304:Cytochromes c; D043262:Ribonuclease P
keywords: Cardiac arrest; Cytochrome c; DNA; Mitochondria; Mortality; Post-cardiac arrest