title: Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis.
abstract: BACKGROUND
  Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelial dysfunction, but the role of ADMA in acute inflammatory states is less well defined.
  
  
  RESULTS
  In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digital microvascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2-4 days later. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baseline plasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45-103]) than in hospital controls (143 [123-166], p<0.0001) and correlated with microvascular reactivity (r = 0.34, R(2) = 0.12, p = 0.02). Baseline plasma ADMA was independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile (≥ 0.66 µmol/L) = 20.8 [2.2-195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase in ADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.
  
  
  CONCLUSIONS
  Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potential mechanism linking increased plasma ADMA with organ failure and death in sepsis.
authors.affiliation: International Health Division, Menzies School of Health Research and Charles Darwin University, Darwin, Northern Territory, Australia. Joshua.Davis@menzies.edu.au
authors.forename: Joshua S
authors.initials: JS
authors.lastname: Davis
authors.forename: Christabelle J
authors.initials: CJ
authors.lastname: Darcy
authors.forename: Tsin W
authors.initials: TW
authors.lastname: Yeo
authors.forename: Catherine
authors.initials: C
authors.lastname: Jones
authors.forename: Yvette R
authors.initials: YR
authors.lastname: McNeil
authors.forename: Dianne P
authors.initials: DP
authors.lastname: Stephens
authors.forename: David S
authors.initials: DS
authors.lastname: Celermajer
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Anstey
mesh_terms: D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000502:physiology; D001682:Biological Availability; D016022:Case-Control Studies; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood / Q000209:etiology / Q000401:mortality; D009569:Nitric Oxide / Q000097:blood / Q000493:pharmacokinetics*; D018805:Sepsis / Q000097:blood / Q000378:metabolism / Q000401:mortality*; D012720:Severity of Illness Index
chemical_list: D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine