title: The L-arginine pathway in acute ischemic stroke and severe carotid stenosis: temporal profiles and association with biomarkers and outcome.
abstract: BACKGROUND
  Endothelial dysfunction is associated with increased levels of asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) resulting in a decreased production of nitric oxide, which regulates the vascular tone.
  
  
  METHODS
  Patients with acute ischemic stroke (AIS, n = 55) and asymptomatic significant carotid stenosis (AsCS, n = 44) were prospectively investigated. L-arginine, ADMA, SDMA, S100 B, and high-sensitivity C-reactive protein (hsCRP) were serially measured within 6 hours after the onset of stroke, at 24 and 72 poststroke hours. All markers were compared with healthy subjects (n = 45). The severity of AIS was daily assessed by National Institute of Health Stroke Scale scoring.
  
  
  RESULTS
  Even within 6 hours after the onset of stroke, L-arginine, ADMA, and SDMA were significantly higher in patients with AIS compared with both AsCS and healthy subjects. S100 B reflecting infarct size, positively correlated with the level of SDMA at 72 poststroke hours; changes in concentration of S100 B positively correlated with changes in the concentration of ADMA by 72 hours. Change in concentration of both ADMA and SDMA correlated with the change in concentration of hsCRP. Concentrations of L-arginine and hsCRP at 72 poststroke hours, respectively, were independent predictors of poststroke infection. S100 B level measured within 6 hours after the onset of AIS and hsCRP at 72 poststroke hours were independent predictors of death.
  
  
  CONCLUSIONS
  Metabolites of the L-arginine pathway were elevated in the very acute phase of ischemic stroke indicating a more pronounced endothelial dysfunction compared with AsCS. An increased basal L-arginine level in patients with AIS might be an adaptive mechanism; such transient elevation of the L-arginine/ADMA ratio at 24 poststroke hours may suggest that a temporary increase of L-arginine along with decrease of ADMA might be related to the protective role of L-arginine. Changes in the L-arginine pathway are predictive of poststroke infections.
authors.affiliation: Department of Anesthesiology and Intensive Care, University of Pecs, Pecs, Hungary. Electronic address: tihamermolnar@yahoo.com.
authors.forename: Tihamer
authors.initials: T
authors.lastname: Molnar
authors.affiliation: Department of Neurology, University of Pecs, Pecs, Hungary.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Pusch
authors.affiliation: Department of Neurology, University of Pecs, Pecs, Hungary.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Papp
authors.affiliation: Department of Neurology, University of Pecs, Pecs, Hungary.
authors.forename: Gergely
authors.initials: G
authors.lastname: Feher
authors.affiliation: Department of Neurology, University of Pecs, Pecs, Hungary.
authors.forename: Laszlo
authors.initials: L
authors.lastname: Szapary
authors.affiliation: Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary.
authors.forename: Bernadett
authors.initials: B
authors.lastname: Biri
authors.affiliation: Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary.
authors.forename: Lajos
authors.initials: L
authors.lastname: Nagy
authors.affiliation: Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary.
authors.forename: Sandor
authors.initials: S
authors.lastname: Keki
authors.affiliation: Department of Neurology, Odense University Hospital, Odense, Denmark; Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Illes
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D015415:Biomarkers / Q000097:blood*; D002097:C-Reactive Protein / Q000032:analysis; D016893:Carotid Stenosis / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D015897:Comorbidity; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D064568:S100 Calcium Binding Protein beta Subunit / Q000097:blood; D020521:Stroke / Q000097:blood* / Q000453:epidemiology / Q000209:etiology
chemical_list: D015415:Biomarkers; D064568:S100 Calcium Binding Protein beta Subunit; C579160:S100B protein, human; C487735:dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine
keywords: L-arginine; asymmetric and symmetric dimethylarginine; carotid stenosis; stroke