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

Temporal Profiles and Association with Biomarkers and Outcome

Tihamer Molnar, Gabriella Pusch, Viktoria Papp, Gergely Feher, Laszlo Szapary, Bernadett Biri, Lajos Nagy, Sandor Keki, Zsolt Illes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftJournal of Stroke & Cerebrovascular Diseases
Vol/bind23
Udgave nummer8
Sider (fra-til)2206–2214
ISSN1052-3057
DOI
StatusUdgivet - 10. jul. 2014

Fingeraftryk

Carotid Stenosis
Nitric Oxide
N,N'-dimethylarginine

Citer dette

Molnar, Tihamer ; Pusch, Gabriella ; Papp, Viktoria ; Feher, Gergely ; Szapary, Laszlo ; Biri, Bernadett ; Nagy, Lajos ; Keki, Sandor ; Illes, Zsolt. / The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis : Temporal Profiles and Association with Biomarkers and Outcome. I: Journal of Stroke & Cerebrovascular Diseases. 2014 ; Bind 23, Nr. 8. s. 2206–2214.
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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.",
author = "Tihamer Molnar and Gabriella Pusch and Viktoria Papp and Gergely Feher and Laszlo Szapary and Bernadett Biri and Lajos Nagy and Sandor Keki and Zsolt Illes",
note = "Copyright {\circledC} 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.",
year = "2014",
month = "7",
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doi = "10.1016/j.jstrokecerebrovasdis.2014.05.002",
language = "English",
volume = "23",
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The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis : Temporal Profiles and Association with Biomarkers and Outcome. / Molnar, Tihamer; Pusch, Gabriella; Papp, Viktoria; Feher, Gergely; Szapary, Laszlo; Biri, Bernadett; Nagy, Lajos; Keki, Sandor; Illes, Zsolt.

I: Journal of Stroke & Cerebrovascular Diseases, Bind 23, Nr. 8, 10.07.2014, s. 2206–2214.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - The L-arginine Pathway in Acute Ischemic Stroke and Severe Carotid Stenosis

T2 - Temporal Profiles and Association with Biomarkers and Outcome

AU - Molnar, Tihamer

AU - Pusch, Gabriella

AU - Papp, Viktoria

AU - Feher, Gergely

AU - Szapary, Laszlo

AU - Biri, Bernadett

AU - Nagy, Lajos

AU - Keki, Sandor

AU - Illes, Zsolt

N1 - Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.

PY - 2014/7/10

Y1 - 2014/7/10

N2 - 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.

AB - 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.

U2 - 10.1016/j.jstrokecerebrovasdis.2014.05.002

DO - 10.1016/j.jstrokecerebrovasdis.2014.05.002

M3 - Journal article

VL - 23

SP - 2206

EP - 2214

JO - Journal of Stroke & Cerebrovascular Diseases

JF - Journal of Stroke & Cerebrovascular Diseases

SN - 1052-3057

IS - 8

ER -