title: Cytochrome C in Patients with Septic Shock.
abstract: OBJECTIVE
  Cytochrome c is an essential component of the electron transport chain, and circulating cytochrome c might be an indicator of mitochondrial injury. The objective of this study was to determine whether cytochrome c levels are elevated in septic patients, whether there is an association between cytochrome c levels and lactate/inflammatory markers, and whether elevated levels of cytochrome c are associated with poor outcomes.
  
  
  METHODS
  This was a single-center, prospective, observational, pilot study within a randomized, placebo-controlled trial. We enrolled adult patients in septic shock and with an elevated lactate (>3 mmol/L). Blood was collected at enrollment and at 12 and 24  h thereafter. Cytochrome c was measured in plasma using an electrochemiluminescence immunoassay.
  
  
  RESULTS
  We included 77 patients. Plasma cytochrome c levels were significantly higher in septic patients than in healthy controls (0.70  ng/mL [quartiles: 0.06, 1.99] vs. 0.19  ng/mL [quartiles: 0.03, 1.32], P = 0.008). Cytochrome c levels at enrollment were positively correlated with lactate levels (r(s) = 0.40, P < 0.001) but not with inflammatory markers. Patients who died before hospital discharge had significantly higher cytochrome c levels than survivors (0.99  ng/mL [quartiles: 0.36, 4.09] vs. 0.58  ng/mL [quartiles: 0.03, 1.64], P = 0.01). When analyzed over time, the difference between survivors and nonsurvivors remained significant (P < 0.001).
  
  
  CONCLUSIONS
  Cytochrome c levels are higher in septic patients than in controls. In unadjusted analysis, septic nonsurvivors had higher cytochrome c levels than survivors.
authors.affiliation: *Center for Resuscitation Science, Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts †Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark ‡Research Center for Emergency Medicine, Aarhus University Hospital, Aarhus, Denmark §Department of Anesthesia Critical Care, Division of Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts ¶Resuscitation Institute at Rosalind Franklin University of Medicine and Science, North Chicago, Illinois ||Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Lars W
authors.initials: LW
authors.lastname: Andersen
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.forename: Sophia
authors.initials: S
authors.lastname: Montissol
authors.forename: Mathias J
authors.initials: MJ
authors.lastname: Holmberg
authors.forename: Christopher
authors.initials: C
authors.lastname: Sulmonte
authors.forename: Julia L
authors.initials: JL
authors.lastname: Balkema
authors.forename: Michael N
authors.initials: MN
authors.lastname: Cocchi
authors.forename: Raúl J
authors.initials: RJ
authors.lastname: Gazmuri
authors.forename: Kathrine M
authors.initials: KM
authors.lastname: Berg
authors.forename: Maureen
authors.initials: M
authors.lastname: Chase
authors.forename: Michael W
authors.initials: MW
authors.lastname: Donnino
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045304:Cytochromes c / Q000097:blood*; D016207:Cytokines / Q000097:blood; D005260:Female; D006801:Humans; D007376:Interleukin-2 / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D018805:Sepsis; D012772:Shock, Septic / Q000097:blood* / Q000401:mortality / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D016207:Cytokines; D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D019344:Lactic Acid; D045304:Cytochromes c