title: Platelet cytochrome c oxidase activity and quantity in septic patients.
abstract: OBJECTIVE
  The cytopathic hypoxia theory proposes that there is an impaired cellular oxygen utilization during sepsis. Respiratory complex IV, or cytochrome c oxidase, was only previously studied in muscle biopsies of 16 surviving and 12 nonsurviving septic patients. We hypothesized that higher activities and quantities of this enzyme complex could be associated with septic patient survival. The objective was to evaluate the relationship between cytochrome c oxidase activities and quantities and 6-month survival in a larger series of septic patients using a less invasive method (circulating platelets).
  
  
  METHODS
  Prospective, multicenter, observational study.
  
  
  METHODS
  The study was carried out in six Spanish intensive care units.
  
  
  METHODS
  We included 96 septic patients.
  
  
  METHODS
  We determined the cytochrome c oxidase activity per citrate synthase activity ratio and cytochrome c oxidase quantity per citrate synthase activity ratio in circulating platelets at the time of diagnosis and related them to 6-month survival. The written informed consent from the family members was obtained.
  
  
  RESULTS
  Survivor patients (n = 54) showed higher cytochrome c oxidase activity per citrate synthase activity ratio (p = .04) and cytochrome c oxidase quantity per citrate synthase activity ratio (p = .006) than nonsurvivors (n = 42). Logistic regression analyses confirmed that the cytochrome c oxidase activity per citrate synthase activity ratio (p = .04) and cytochrome c oxidase quantity per citrate synthase activity ratio (p = .02) were independent predictors of 6-month survival. The area under the curve to predict 6-month survival was 0.62 (95% confidence interval 0.51-0.74; p = .04) for the cytochrome c oxidase activity per citrate synthase activity ratio and 0.67 (95% confidence interval 0.56-0.76; p = .003) for the cytochrome c oxidase quantity per citrate synthase activity ratio. A negative correlation was found between the cytochrome c oxidase quantity per citrate synthase activity ratio and Sepsis-Related Organ Failure Assessment score (p = .04).
  
  
  CONCLUSIONS
  Platelet cytochrome c oxidase activity and quantity were independent predictors of 6-month survival and could be used as biomarkers of sepsis mortality. This is a rapid, easy, and less invasive protocol to assess mitochondrial function. Patients with lower cytochrome c oxidase activity and quantity could benefit from drugs that improve mitochondrial function.
authors.affiliation: Intensive Care Unit, Hospital Universitario de Canarias, La Laguna, Santa Cruz de Tenerife, Spain. lorentemartin@msn.com
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lorente
authors.forename: María M
authors.initials: MM
authors.lastname: Martín
authors.forename: Esther
authors.initials: E
authors.lastname: López-Gallardo
authors.forename: Ruth
authors.initials: R
authors.lastname: Iceta
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.forename: José
authors.initials: J
authors.lastname: Blanquer
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Labarta
authors.forename: César
authors.initials: C
authors.lastname: Díaz
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
authors.forename: Noelia
authors.initials: N
authors.lastname: Lafuente
authors.forename: Miriram
authors.initials: M
authors.lastname: Hernández
authors.forename: Froilán
authors.initials: F
authors.lastname: Méndez
authors.forename: Nuria
authors.initials: N
authors.lastname: Medina
authors.forename: José M
authors.initials: JM
authors.lastname: Ferrer-Agüero
authors.forename: José
authors.initials: J
authors.lastname: Ferreres
authors.forename: Maria C
authors.initials: MC
authors.lastname: LLimiñana
authors.forename: María L
authors.initials: ML
authors.lastname: Mora
authors.forename: Santiago
authors.initials: S
authors.lastname: Lubillo
authors.forename: Manuel
authors.initials: M
authors.lastname: Sánchez-Palacios
authors.forename: Julio
authors.initials: J
authors.lastname: Montoya
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ruiz-Pesini
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000201:enzymology; D002950:Citrate (si)-Synthase / Q000378:metabolism; D015331:Cohort Studies; D003576:Electron Transport Complex IV / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D018805:Sepsis / Q000201:enzymology* / Q000401:mortality*; D015996:Survival Rate
chemical_list: D015415:Biomarkers; D003576:Electron Transport Complex IV; D002950:Citrate (si)-Synthase