Effect of L-Arginine Therapy on Vasospasm: Experimental Study in Rats

Akar, Ezgi; Emon, Selin Tural; Uslu, Serap; Orakdogen, Metin; Somay, Hakan

doi:10.1016/j.wneu.2019.08.119

Cited by 8 publications

(5 citation statements)

References 13 publications

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“…Indeed, a protective effect for L-arginine administration after experimental traumatic brain injury or vasospasm after subarachnoid hemorrhage has previously been reported. 40,41 L-Arginine substitution after brain injury has been shown to increase brain tissue NO levels and cerebral blood flow. 42 However, L-arginine supplementation in experimental ischemic stroke showed no benefit despite increased cortical blood flow whereas other NO donors reduced lesion volume.…”

Section: Impact Of Early Alterations In L-arginine Metabolism On Neurological Outcomementioning

confidence: 99%

Intrathecal and systemic alterations of L-arginine metabolism in patients after intracerebral hemorrhage

Mader

Böger

Appel

et al. 2021

J Cereb Blood Flow Metab

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Alterations in the concentration of nitric oxide (NO) and L-arginine metabolites have been associated with the pathophysiology of different vascular diseases. Here, we describe striking changes in L-arginine metabolism after hemorrhagic stroke. Blood and cerebrospinal fluid (CSF) samples of patients with intracerebral hemorrhage (ICH) and/or intraventricular hemorrhage were collected over a ten-day period. Liquid chromatography-tandem mass spectrometry was used to quantify key substrates and products of L-arginine metabolizing enzymes as well as asymmetric (ADMA) and symmetric dimethylarginine (SDMA). Changes in the plasma were limited to early reductions in L-ornithine, L-lysine, and L-citrulline concentrations. Intrathecally, we observed signs of early NO synthase (NOS) upregulation followed by a decrease back to baseline accompanied by a rise in the level of its endogenous NOS-inhibitor ADMA. SDMA demonstrated increased levels throughout the observation period. For arginase, a pattern of persistently elevated activity was measured and arginine:glycine amidinotransferase (AGAT) appeared to be reduced in its activity at later time points. An early reduction in CSF L-arginine concentration was an independent risk factor for poor outcome. Together, these findings further elucidate pathophysiological mechanisms after ICH potentially involved in secondary brain injury and may reveal novel therapeutic targets.

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Section: Impact Of Early Alterations In L-arginine Metabolism On Neurological Outcomementioning

confidence: 99%

Intrathecal and systemic alterations of L-arginine metabolism in patients after intracerebral hemorrhage

Mader

Böger

Appel

et al. 2021

J Cereb Blood Flow Metab

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“…Additionally, restoration of Arg/Orn by intrathecal application of L-arginine could be a promising approach to prevent CVS and DCI and improve clinical outcome in SAH patients with reduced Arg/Orn. Indeed, intracisternal or intraperitoneal injection of L-arginine reversed experimental vasospasm in dogs [43] and rats [44]. Intracarotid infusion of L-arginine led to a markedly increased regional cerebral blood flow, but did not influence the incidence of CVS in a primate model of SAH [45], possibly due to the short half-life of L-arginine.…”

Section: Discussionmentioning

confidence: 97%

Arginase-1 Released into CSF After Aneurysmal Subarachnoid Hemorrhage Decreases Arginine/Ornithine Ratio: a Novel Prognostic Biomarker

Zimmermann

Weller

Grub

et al. 2021

Transl. Stroke Res.

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We hypothesized that the enzyme arginase-1 is released into the cerebrospinal fluid (CSF) during red blood cell lysis and contributes to dysregulated metabolism of the nitric oxide (NO) precursor L-arginine during aneurysmal subarachnoid hemorrhage (SAH). This prospective case–control study included 43 patients with aneurysmal SAH and ventricular drainage for clinical reasons. Longitudinal CSF samples (99) were obtained in the course of SAH. Patients were dichotomized regarding the occurrence of cerebral vasospasm syndrome (CVS) (N = 19). Arginase-1 and the amino acids L-arginine and L-ornithine were quantified in CSF. Outcome assessments included delayed cerebral ischemia (DCI) and functional status after 3 months using the modified Rankin Scale (mRS). Arginase-1 was released into the CSF of SAH patients whereas this enzyme was undetectable in controls. Compared to patients without CVS, arginase-1 levels were higher in CVS patients until day 14 after clinical event. The well-known surrogate parameter for arginase acitivity, the L-arginine to L-ornithine ratio (Arg/Orn), correlated with CSF arginase-1 levels. Arg/Orn was reduced in patients with CVS from disease onset (days 1–3, p = 0.0009) until day 14. Logistic regression analysis of early Arg/Orn was predictive for CVS (p = 0.008) and DCI (p = 0.035), independent of age, Hunt and Hess grade, and intraventricular blood. Arg/Orn < 2.71 at disease onset predicted CVS with a sensitivity of 86.7% and specificity of 72.2%. Arg/Orn ≥ 2.71 predicted excellent functional outcome. We propose a novel mechanism contributing to NO deprivation during SAH: arginase-1 is released from erythrocytes into the CSF, leading to L-arginine consumption and reduced NO bioavailability. Furthermore, Arg/Orn is a robust predictor for occurrence of CVS, DCI, and functional outcome 3 months after aneurysmal SAH. Our data provide a novel prognostic biomarker and may contribute to the development of novel therapeutic strategies in SAH. Clinical Trial Registration-URL: http://www.drks.de. Unique identifier: DRKS00015293, date of registration: 13.09.2018.

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“…However, the exact mechanism of the occurrence and development of vasospasm has not been fully revealed. 7 - 9 It has been shown that the risk of vasospasm is significantly correlated with the amount of SAH, and erythrocyte degradation in the subarachnoid space synchronizes with the onset of vasospasm. 10 , 11 Thus, it is speculated that erythrocyte degradation products may be one of the inducing factors of vasospasm.…”

Section: Discussionmentioning

confidence: 99%

Analysis on efficacy of compound dextran combined with atorvastatin calcium in patients with CVS caused by SAH based on TCD blood flow indexes

Ma¹,

Gan²,

Su³

et al. 2022

Pak J Med Sci

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Objectives: To analyze the effects of compound dextran combined with atorvastatin calcium on blood flow indexes, peroxidase 2 (Prx2) and endothelin-1 (ET-1) in patients with cerebral vasospasm (CVS) caused by subarachnoid hemorrhage (SAH). Methods: One hundred patients with CVS caused by SAH treated in Baoding No.1 Central Hospital from January 2019 to December 2020 were divided into observation group and control group. The control group was treated with atorvastatin calcium tablets, while the observation group was additionally treated with compound dextran. The hospital stays, Glasgow Outcome Scale (GOS), hemoglobin (Hb) and hematocrit (Hct) levels before and five days after treatment were recorded. The hemodynamic parameters of the middle cerebral artery (MCA) and the serum levels of Prx2 and ET-1 were detected. Results: After treatment, GOS and Hct levels in the observation group were both higher than those in the control group (P < 0.05). After treatment, the mean and peak velocities of the MCA in the observation group were significantly lower than those in the control group (P < 0.05). After treatment, the serum levels of Prx2 and ET-1 in the observation group were significantly lower compared with those in the control group (P < 0.05). However, no significant differences were found in the incidences of adverse reactions between the two groups (P > 0.05). Conclusions: Compound dextran combined with atorvastatin calcium can effectively enhance clinical efficacy, improve cerebral blood flow and reduce serum Prx2 and ET-1 levels in patients with CVS caused by SAH. doi: https://doi.org/10.12669/pjms.38.8.5504 How to cite this:Zhang Y, Ma F, Gan N, Su F, Song Z. Analysis on efficacy of compound dextran combined with atorvastatin calcium in patients with CVS caused by SAH based on TCD blood flow indexes. Pak J Med Sci. 2022;38(8):---------. doi: https://doi.org/10.12669/pjms.38.8.5504 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Effect of L-Arginine Therapy on Vasospasm: Experimental Study in Rats

Cited by 8 publications

References 13 publications

Intrathecal and systemic alterations of L-arginine metabolism in patients after intracerebral hemorrhage

Intrathecal and systemic alterations of L-arginine metabolism in patients after intracerebral hemorrhage

Arginase-1 Released into CSF After Aneurysmal Subarachnoid Hemorrhage Decreases Arginine/Ornithine Ratio: a Novel Prognostic Biomarker

Analysis on efficacy of compound dextran combined with atorvastatin calcium in patients with CVS caused by SAH based on TCD blood flow indexes

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