Nitric oxide metabolites in the cisternal cerebral spinal fluid of patients with subarachnoid hemorrhage.

Abstract

To investigate nitric oxide (NO) metabolism after subarachnoid hemorrhage (SAH). We measured the concentrations of the NO metabolites, nitrite and nitrate, in cerebrospinal fluid (CSF) obtained from the cisternal drainage of patients with SAH. Studies were performed for 31 patients who had undergone surgical obliteration of bleeding aneurysms within 3 days of their hemorrhage. The concentrations of nitrite and nitrate in the CSF were measured for 14 days using a nitrate/nitrite kit and samples that were obtained on a daily basis from the cisternal drainage. Compared with the control values in the CSF (2.6 +/- 0.4 mumol/L, n = 14) obtained from patients with hemifacial spasm, trigeminal neuralgia, or nonruptured aneurysms, the concentrations of nitrite and nitrate in the CSF were significantly elevated in the acute stage of SAH and remained elevated. The concentration of NO metabolites may correlate with the amount of bleeding, inasmuch as the values in patients in Fisher Group 3 (n = 25) were higher than those in patients in Fisher Group 2 (n = 6). The concentration of nitrate was higher than that of nitrite, suggesting that NO in the subarachnoid space is mainly absorbed by hemoglobin and degraded to nitrate. No differences were demonstrated in patients treated with high doses of methylprednisolone (n = 17) compared with those treated with usual-dose steroids (n = 14). Steroids are known to prevent the formation of inducible NO synthase mediated by inflammatory cytokines. NO metabolism in the brain is stimulated after SAH. Nitrate is the dominant NO metabolite in CSF after SAH. The involvement of inducible NO synthase in the pathophysiology of NO metabolism after SAH was not clearly suggested based on the present data.