Low Plasma Arginine:Asymmetric Dimethyl Arginine Ratios Predict Mortality After Intracranial Aneurysm Rupture

Staalsø, Jonatan Myrup; Bergström, Anita; Edsen, Troels; Weikop, Pia; Romner, Bertil; Olsen, Niels Vidiendal

doi:10.1161/strokeaha.111.000605

Cited by 27 publications

(21 citation statements)

References 51 publications

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“…A study by Staalso et al, found that low arginine:ADMA ratio in the first week after SAH is predictive of mortality during the first thirty days (37). Interestingly, high ADMA levels are associated to increased mortality in cardiac pathologies, such as coronary artery disease, chronic heart failure, and peripheral artery disease.…”

Section: Hormones/enzymesmentioning

confidence: 99%

“…Finally, another investigation, carried on in 111 patients, reported that a low arginine/ADMA (asymmetric dimethylarginine) ratio in the first week after SAH is predictive of mortality during the first 30 days and that inversely correlates with nitrite/nitrate levels (37).…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

“…ADMA is an inhibitor of NOS, which can lead to endothelial dysfunction associated with vasospasm (37). However, since arginine:ADMA ratio remain stable over time after SAH, it is not clear whether changes in ADMA levels have a role in endothelial dysfunction or are a consequence of vascular damage (37). Noticeably, the same author showed that middle cerebral artery velocity inversely correlated with nitrite/nitrate levels, but not with ADMA and arginine:ADMA levels, suggesting that nitrite/nitrate ratio is more important than the arginine pathway in regulating blood flow after SAH (37).…”

Section: Hormones/enzymesmentioning

confidence: 99%

“…Unfortunately, eighty-five to ninety percent of unruptured aneurysms are asymptomatic (16). Genetic and environmental factors, such as hypertension, smoking, alcohol consumption, female gender, and age >50 years, have been associated with an increased chance of harboring an IA (2,8,16,19,23,33,37,42); however, even in the presence of such risk factors, IA formation and rupture is extremely hard to predict and stage because the pathogenesis of IA is unclear. Therefore, the analysis of biomarkers can help us understand IA formation and progression which can be crucial to help prevent the devastating consequences of rupture and improve patient management (2,20,31).…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Search for Biomarkers of Intracranial Aneurysms: A Systematic Review

et al. 2015

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Section: Hormones/enzymesmentioning

confidence: 99%

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

Section: Hormones/enzymesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Search for Biomarkers of Intracranial Aneurysms: A Systematic Review

et al. 2015

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“…We read with great interest the article by Staalsø et al 1 pertaining to the relationship between asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, and survival in patients with aneurysmal subarachnoid hemorrhage. The results of their study demonstrated that a low arginine:ADMA ratio in the first week after subarachnoid hemorrhage predicted mortality rate in the first 30 days.…”

Section: To the Editormentioning

confidence: 99%

Letter by Tsuda Regarding Article, “Low Plasma Arginine:Asymmetric Dimethyl Arginine Ratios Predict Mortality After Intracranial Aneurysm Rupture”

Tsuda

2013

Stroke

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We read with great interest the article by Staalsø et al 1 pertaining to the relationship between asymmetrical dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, and survival in patients with aneurysmal subarachnoid hemorrhage. The results of their study demonstrated that a low arginine:ADMA ratio in the first week after subarachnoid hemorrhage predicted mortality rate in the first 30 days. The arginine:ADMA ratio was negatively correlated with the serum NO-metabolite levels. In addition, the arginine:ADMA ratio was higher in good grade patients, but did not change significantly overtime. The authors proposed that plasma arginine:ADMA ratio might be associated with the pathophysiology in the subacute phase after subarachnoid hemorrhage, affecting the mortality rate possibly through modulation of cerebral blood flow.Evidence indicates that NO may actively participate in neuroprotection in cerebral ischemia. In a study presented previously, we investigated the relationship between NO and membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells by means of an electron spin resonance method.2,3 Reduced membrane fluidity of red blood cells might cause a disturbance in the blood rheological behavior and microcirculation, which could contribute, at least in part, to the pathophysiology of circulatory disorders. We demonstrated that an NO donor increased membrane fluidity of red blood cells and improved the rigidity of cell membranes in hypertensive and normotensive subjects.2 In the separate series of the study, we reported that reduced membrane fluidity of red blood cells was associated with decreased NO-metabolites and increased ADMA levels in plasma. 3 The findings might support the hypothesis that NO would be a defense against vascular complications in circulatory disorders, which would be in accordance with the present result of Staalsø et al.Recently, it has been shown that not only ADMA, but also its analogue symmetrical dimethylarginine (SDMA) might have a pivotal role in the progression of stroke. It was reported that higher SDMA levels in the cerebrospinal fluid were correlated with a poor outcome at 3 months after stroke onset. 4 Worthmann et al 5 demonstrated that an increase of both plasma ADMA and SDMA levels within the first 72 hours after the onset of ischemic stroke may predict a poor outcome. In this context, it is strongly suggested that both ADMA and SDMA could be the biomarkers referring to endothelial dysfunction and disturbed cerebrovascular circulation. Therefore, we would like to know whether SDMA alone, or in combination with ADMA and arginine, might have a predictive value for the outcome of subarachnoid hemorrhage in the study of Staalsø et al. It would be important to assess more precisely the relationships between endogenous NO synthase inhibitors and circulatory dysfunction in the brain, and their role in determining the outcome of cerebrovascular disorders. DisclosuresNone.

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A novel mass spectrometry‐based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l‐arginine and l‐citrulline optimized for LC‐MS‐TOF and LC‐MS/MS

Wiśniewski

Fleszar

Piechowicz

et al. 2017

Biomedical Chromatography

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Nitric oxide (NO) is a regulatory molecule involved in many biological processes. NO is produced by nitric oxide synthase by conversion of l-arginine to l-citrulline. l-Arginine methylated derivatives, asymmetric and symmetric dimethylarginines (asymmetric dimethylarginine, ADMA, and symmetric dimethylarginine, SDMA), regulate l-arginine availability and the activity of nitric oxide synthase. As such, they have been frequently investigated as potential biomarkers in pathologies associated with dysfunctions in NO synthesis. Here, we present a new multistep analytical methodology based on liquid chromatography combined with mass spectrometry for the accurate identification of l-arginine, l-citrulline, ADMA and SDMA. Compounds are measured as stable 2,3,4,5,6-pentafluorobenzoyl chloride derivatives, which allows for simultaneous analysis of all compounds through chromatographic separation of ADMA and SDMA using a reverse-phase column. Serum aliquots (100 μL) were spiked with isotope-labeled internal standards and sodium carbonate buffer. The derivatization process was carried out at 25°C for 10 minu using pentafluorobenzoyl chloride as derivatization reagent. Calibration demonstrated good linearity (R = 0.9966-0.9986) for all derivatized compounds. Good accuracy (94.67-99.91%) and precision (1.92-11.8%) were observed for the quality control samples. The applicability of the method was evaluated in a cohort of angiological patients and healthy volunteers. The method discerned significantly lower l-arginine and l-citrulline in angiologic patients. This robust and fast LC-ESI-MS method may be a useful tool in quantitative analysis of l-arginine, ADMA, SDMA and l-citrulline.

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Low Plasma Arginine:Asymmetric Dimethyl Arginine Ratios Predict Mortality After Intracranial Aneurysm Rupture

Cited by 27 publications

References 51 publications

Search for Biomarkers of Intracranial Aneurysms: A Systematic Review

Search for Biomarkers of Intracranial Aneurysms: A Systematic Review

Letter by Tsuda Regarding Article, “Low Plasma Arginine:Asymmetric Dimethyl Arginine Ratios Predict Mortality After Intracranial Aneurysm Rupture”

A novel mass spectrometry‐based method for simultaneous determination of asymmetric and symmetric dimethylarginine, l‐arginine and l‐citrulline optimized for LC‐MS‐TOF and LC‐MS/MS

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