Molnar, Tihamer2; Pusch, Gabriella3; Papp, Viktoria3; Feher, Gergely3; Szapary, Laszlo3; Biri, Bernadett4; Nagy, Lajos4; Keki, Sandor4; Illes, Zsolt5
1 Neurology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU2 Department of Anesthesiology and Intensive Care, University of Pecs, Pecs, Hungary. Electronic address: firstname.lastname@example.org Department of Neurology, University of Pecs, Pecs, Hungary.4 Department of Applied Chemistry, University of Debrecen, Debrecen, Hungary.5 Neurology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU
Temporal Profiles and Association with Biomarkers and Outcome
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.
Journal of Stroke and Cerebrovascular Diseases, 2014, Vol 23, Issue 8