Nitric oxide and subarachnoid hemorrhage: Elevated levels in cerebrospinal fluid and their implications

OBJECTIVE: Nitric oxide (NO) plays an important role in the pathogenesis of neuronal injury after brain ischemia, and decreased levels of NO have been implicated in the pathogenesis of vasospasm after subarachnoid hemorrhage (SAH). In this study, we measured the ventricular cerebrospinal fluid (CSF) NO levels in patients with SAH and correlated the levels with clinical grade and middle cerebral artery velocities measured with transcranial Doppler ultrasound. METHODS: All patients with spontaneous SAH documented on computed tomography and with an external ventricular drain inserted within 24 hours of hemorrhage were included in the study. A total of 16 patients were studied between August 1999 and August 2000. CSF was collected serially at the time of surgery and subsequently at daily intervals. it was collected during the time that the external ventricular drain remained patent and in situ. NO levels were measured by photometric analysis by using a nitrite/nitrate assay kit (Cayman Chemical, Ann Arbor, MI). RESULTS: The peak NO level in patients with SAH ranged from 9.96 to 168.16 mu mol, with a median of 36.93 mu mol. The levels were significantly elevated as compared with the control group (5.16 mu mol, P < 0.05). The median NO level in patients with poor-grade SAH was 67.14 <mu>mol as compared with 27.42 mu mol in patients with good-grade hemorrhage (P < 0.05). No correlation was seen between CSF NO levels and middle cerebral artery velocities. The median NO level was 33.2 <mu>mol in patients with a poor outcome as compared with 30.25 mu mol in patients with a good outcome (P > 0.05). CONCLUSION: This study showed that NO levels are elevated after spontaneous SAH, and the degree of elevation is higher in patients with poor-grade SAH.