The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis: 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.