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Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis

Davis, Joshua S., Darcy, Christabelle J., Yeo, Tsin W., Jones, Catherine, McNeil, Yvette R., Stephens, Dianne P., Celermajer, David S. and Anstey, Nicholas M. (2011). Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis. PLoS ONE,6(2):e17260.

Document type: Journal Article
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Title Asymmetric dimethylarginine, endothelial nitric oxide bioavailability and mortality in sepsis
Author Davis, Joshua S.
Darcy, Christabelle J.
Yeo, Tsin W.
Jones, Catherine
McNeil, Yvette R.
Stephens, Dianne P.
Celermajer, David S.
Anstey, Nicholas M.
Journal Name PLoS ONE
Publication Date 2011
Volume Number 6
Issue Number 2
ISSN 1932-6203   (check CDU catalogue open catalogue search in new window)
Start Page e17260
Total Pages 6
Place of Publication United States
Publisher Public Library of Science
HERDC Category C1 - Journal Article (DEST)
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.

Methods and 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, R2 = 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 mmol/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.

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.
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