Sviri Gill E, Shik V, Raz B, Soustiel J F
Department of Neurosurgery, Rambam Medical Center and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa, Israel.
Acta Neurochir (Wien). 2003 Oct;145(10):851-60; discussion 860. doi: 10.1007/s00701-003-0101-7.
Brain natriuretic peptide (BNP) is a potent natriuretic factor responsible for hyponatremia observed in patients with SAH. Through its systemic effects (reduction of blood volume and blood pressure) BNP may augment cerebral blood flow reduction and ischemia secondary to vasospasm. The purpose of the present study was to evaluate the relationship between BNP plasma concentration during the first 12 days following SAH and the development of cerebral vasospasm (CVS). The authors propose a hypothesis for the role played by natriuretic peptides in the pathophysiology of cerebral vasospasm based on the present findings and review the literature.
Thirty eight patients with spontaneous SAH were prospectively included in the present study. BNP plasma concentrations were assessed at four different time periods following SAH (day 1-3, 4-6, 7-9, 10-12). TCD evidence of CVS was found in 26 patients (68.5%), fourteen patients (36.8%) had delayed ischemic neurological deficits (DIND).
Initial BNP plasma concentrations were significantly more elevated in patients who eventually did not develop DIND (95.07+/-107.65 pg/ml vs. 25.81+/-22.57 pg/ml, p=0.0053). However, in patients with DIND, the BNP plasma concentration increased by 3.69 ( p<0.05), 5.89 ( p<0.001) and 4.54 fold ( p<0.001) between days 1-3 to days 4-6, 7-9 and 10-12 respectively (day 1 was regarded as the day of hemorrhage). In patients without CVS or asymptomatic CVS the BNP plasma concentration decreased between days 1-3 to day 10-12. A similar trend in BNP plasma concentration was found in patients with severe SAH (Fisher's score 3-4) as compared with patients with non visible or moderate SAH (BNP concentration ratio day 7-9/1-3: 4.37 vs. 0.75, p=0.015; day 10-12/1-3: 3.37 vs. 0.3, p=0.0144). The trend in BNP plasma concentration between day 1-3 to day 7-9 was found to correlate with CVS severity with an average increase of 2.01, 3.8 and 5.44 fold for mild, moderate and severe VS respectively ( p<0.01, r=0.4174).
These results suggest that BNP secretion in SAH patients is closely related to the bleeding intensity and vasospasm severity as well as to development of DIND with a progressive and marked increase during the clinical course in patients who eventually develop cerebral ischemia. Taken together the local and systemic effects of BNP on CBF suggest that BNP might play a role in the pathophysiology of CVS through its systemic effects on blood pressure and plasma volume BNP leading to an aggravation of brain ischemia secondary to vasospasm.
脑钠肽（BNP）是一种强效利钠因子，可导致蛛网膜下腔出血（SAH）患者出现低钠血症。通过其全身效应（减少血容量和血压），BNP可能会加剧因血管痉挛继发的脑血流量减少和缺血。本研究的目的是评估SAH后前12天内血浆BNP浓度与脑血管痉挛（CVS）发生之间的关系。作者基于目前的研究结果，提出了关于利钠肽在脑血管痉挛病理生理学中所起作用的假设，并对相关文献进行了综述。
本研究前瞻性纳入了38例自发性SAH患者。在SAH后的四个不同时间段（第1 - 3天、4 - 6天、7 - 9天、10 - 12天）评估血浆BNP浓度。26例患者（68.5%）有CVS的经颅多普勒（TCD）证据，14例患者（36.8%）出现了迟发性缺血性神经功能缺损（DIND）。
最终未发生DIND的患者初始血浆BNP浓度显著更高（95.07±107.65 pg/ml对25.81±22.57 pg/ml，p = 0.0053）。然而，在发生DIND的患者中，血浆BNP浓度在第1 - 3天至第4 - 6天、7 - 9天和10 - 12天分别增加了3.69倍（p < 0.05）、5.89倍（p < 0.001）和4.54倍（p < 0.001）（第1天视为出血日）。在没有CVS或无症状CVS的患者中，血浆BNP浓度在第1 - 3天至第10 - 12天有所下降。与非可见或中度SAH患者相比，重度SAH（Fisher评分3 - 4）患者的血浆BNP浓度也有类似趋势（第7 - 9天/第1 - 3天的BNP浓度比值：4.37对0.75，p = 0.015；第10 - 12天/第1 - 3天：3.37对0.3，p = 0.0144）。发现第1 - 3天至第7 - 9天血浆BNP浓度的变化趋势与CVS严重程度相关，轻度、中度和重度血管痉挛（VS）时平均分别增加2.01倍、3.8倍和5.44倍（p < 0.01，r = 0.4174）。
这些结果表明，SAH患者的BNP分泌与出血强度、血管痉挛严重程度以及DIND的发生密切相关，在最终发生脑缺血的患者临床过程中呈进行性且显著增加。综合BNP对脑血流量的局部和全身效应表明，BNP可能通过其对血压和血浆容量的全身效应在CVS的病理生理学中发挥作用，导致血管痉挛继发脑缺血加重。
