Serum and urine nitrate and nitrite are not reliable indicators of intrathecal nitric oxide production in acute brain injury

This study examined the correlation between nitric oxide (NO) metabolites in the three major body fluid compartments and assessed performance of newly described vanadium-based assay for simultaneous detection of nitrite and nitrate (NO_x) in human samples. Vanadium reduces nitrate to nitrite, which can be measured after a colorimetric reaction with Griess reagents. Cisternal cerebro spinal fluid (CSF), serum and urine samples from 10 patients with acute brain injury (ABI) were compared to control subjects. Significantly higher CSF NO_x levels were found in brain injury patients compared to control patients (19.7±13.7 vs. 6.5±2.3 μM; p=0.01), which persisted for 10-day period of observation. The serum and urine levels of NO_x on admission were not statistically different (42.8±28.2 μM; 584.1±337.8 μmol/g Cr, respectively) from controls (36.8±14.8 μM; 819.7±356.0 μmol/g Cr), but tended to decrease during the disease course reaching the lowest level on day 6 (serum: 19.3±8.4 μM, urine: 300.4±111.9 μmol/g Cr). CSF levels of NO_x correlated moderately with those in serum (p=0.001, R=0.5). Serum NO_x concentrations correlated weakly with urine levels (p=0.04, R=0.3). There was no significant correlation between CSF NO_x and urine NO_x levels. In conclusion, patients suffering brain injury had increased NO_x concentrations in CSF, which remained independent from other body fluid compartments. Serum and urinary NO_x levels cannot be used as a reliable index to assess intrathecal NO production.