Asymmetric and Symmetric Dimethylarginines are Markers of Delayed Cerebral Ischemia and Neurological Outcome in Patients with Subarachnoid Hemorrhage
Asymmetric and Symmetric Dimethylarginines are Markers of Delayed Cerebral Ischemia and Neurological Outcome in Patients with Subarachnoid Hemorrhage
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DOI：
10.1007/s12028-018-0520-1
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发表时间：
2018-08-01
影响因子：
3.5
通讯作者：
Hannemann, Juliane
中科院分区：
文献类型：
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作者：
Appel, Daniel;Seeberger, Miriam;Hannemann, Juliane
迟发性脑缺血（DCI）是原发性蛛网膜下腔出血（SAH）后患者死亡和神经元损伤的主要原因。不对称和对称二甲基精氨酸（ADMA和SDMA）通过不同的机制抑制L-精氨酸产生一氧化氮。ADMA水平升高与SAH后血管痉挛相关。我们的目的是研究血浆和脑室脑脊液（CSF）中ADMA和SDMA的时间过程及其与DCI和outcome.We测定ADMA和SDMA在34 SAH患者与脑室外引流在入院时和第3，6，8，12，15天，并随访他们的临床状态和神经功能的结果，直到出院后30天。DCI定义为脑计算机断层扫描或磁共振成像上出现新的梗死灶。基线时，DCI患者（N = 14; 41%）和非DCI患者的ADMA和SDMA血浆浓度无显著差异;然而，DCI患者的血浆ADMA在出血后第8天和第15天达到峰值（0.81-0.91 A μ mol/l）。基线血浆l-精氨酸/ADMA比率在患有DCI的患者中显著较低（57.1 [34.3; 70.8] vs. 68.7 [55.7; 96.2]; p < 0.05）。DCI患者CSF中ADMA和SDMA浓度显著高于无DCI患者。在多变量校正线性回归模型中，CSF ADMA与DCI的发生率呈负相关（OR 0.03 [0.02-0.70]; p = 0.04），而出血当天的CSF SDMA预测出院后30天内神经功能结局较差（OR 22.4 [1.21-416.02]; p = 0.04）。我们的研究表明ADMA和l-精氨酸/ADMA比值与SAH后DCI的发生率相关。相比之下，SDMA与SAH后的初始神经元损伤和不良神经功能结局相关。这些数据支持ADMA和l-精氨酸影响SAH后脑缺血的病理生理学的假设，而SDMA是SAH后神经学结果的生物标志物。
Delayed cerebral ischemia (DCI) is the major cause of lethality and neuronal damage in patients who survived the primary subarachnoid hemorrhage (SAH). Asymmetric and symmetric dimethylarginines (ADMA and SDMA) inhibit nitric oxide production from l-arginine via distinct mechanisms. Elevated ADMA levels are associated with vasospasm after SAH. We aimed to study the time course of ADMA and SDMA in plasma and ventricular cerebrospinal fluid (CSF) and their associations with DCI and outcome.We measured ADMA and SDMA in 34 SAH patients with an external ventricular drain at admission and on days 3, 6, 8, 12, and 15 and followed them up for clinical status and neurological outcome until 30 days post-discharge. DCI was defined as the appearance of new infarctions on cerebral computed tomography or magnetic resonance imaging.ADMA and SDMA plasma concentrations did not differ significantly at baseline between patients who suffered DCI (N = 14; 41%) and not; however, plasma ADMA reached a peak on days 8 and 15 after hemorrhage in patients with DCI (0.81-0.91 A mu mol/l). Baseline plasma l-arginine/ADMA ratio was significantly lower in patients with DCI (57.1 [34.3; 70.8] vs. 68.7 [55.7; 96.2]; p < 0.05). ADMA and SDMA concentrations in CSF were significantly higher in patients with DCI than without. In multivariable-adjusted linear regression models, CSF ADMA was negatively associated with the incidence of DCI (OR 0.03 [0.02-0.70]; p = 0.04), whereas CSF SDMA on the day of hemorrhage predicted poor neurological outcome until 30 days after discharge (OR 22.4 [1.21-416.02]; p = 0.04).Our study shows that ADMA and the l-arginine/ADMA ratio are associated with the incidence of DCI after SAH. By contrast, SDMA was associated with initial neuronal damage and poor neurological outcome after SAH. These data support the hypothesis that ADMA and l-arginine affect the pathophysiology of cerebral ischemia after SAH, while SDMA is a biomarker of neurological outcome after SAH.