title: Pyruvate Dehydrogenase Activity Is Decreased in the Peripheral Blood Mononuclear Cells of Patients with Sepsis. A Prospective Observational Trial.
abstract: BACKGROUND
  Rodent studies have shown that pyruvate dehydrogenase (PDH) levels are low in sepsis. This may cause cells to shift to anaerobic metabolism, resulting in increased lactate production. Alterations in PDH during sepsis have never been studied in humans.
  
  
  OBJECTIVE
  The objective of this pilot study was to measure PDH activity and quantity in patients with severe sepsis.
  
  
  METHODS
  We conducted a pilot case-control study at a single urban tertiary care center. We compared PDH activity and quantity between patients with severe sepsis admitted to the intensive care unit and healthy control subjects. PDH activity and quantity were measured in isolated peripheral blood mononuclear cells. We measured PDH activity and quantity in control subjects at baseline and in patients with sepsis at 0 (baseline), 24, 48, and 72 hours.
  
  
  RESULTS
  We enrolled 56 patients with sepsis and 20 control subjects with at least one blood sample being drawn from each patient. PDH activity and quantity in the sepsis group were significantly lower than the control group (P < 0.001). In multivariable linear regression adjusting for age, race, sex, and assay plate, the difference remained significant. Patients with sepsis who died had significantly lower PDH activity compared with those who survived (P = 0.03).
  
  
  CONCLUSIONS
  PDH activity and quantity is decreased in peripheral blood mononuclear cells of humans with severe sepsis when compared with healthy control subjects, and may be associated with mortality. Whether decreased PDH activity plays a role in lactate metabolism or whether pharmacologic modification of PDH activity may improve outcomes remains unknown.
authors.affiliation: 1 Department of Internal Medicine.
authors.forename: Erin
authors.initials: E
authors.lastname: Nuzzo
authors.affiliation: 2 Division of Pulmonary, Critical Care, and Sleep, and.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Berg
authors.affiliation: 3 Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.|4 Department of Anesthesiology, Aarhus University Hospital, Aarhus, Denmark; and.
authors.forename: Lars W
authors.initials: LW
authors.lastname: Andersen
authors.affiliation: 3 Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Julia
authors.initials: J
authors.lastname: Balkema
authors.affiliation: 3 Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Sophia
authors.initials: S
authors.lastname: Montissol
authors.affiliation: 3 Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.|5 Anesthesia, and Critical Care, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Cocchi
authors.affiliation: 3 Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Liu
authors.affiliation: 2 Division of Pulmonary, Critical Care, and Sleep, and.|3 Department of Emergency Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Donnino
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D011768:Pyruvate Dehydrogenase Complex / Q000097:blood*; D018805:Sepsis / Q000201:enzymology*; D062606:Tertiary Care Centers
chemical_list: D011768:Pyruvate Dehydrogenase Complex
keywords: aerobic; lactate; metabolism; mitochondria; mortality