Relation of Cerebral Energy Metabolism and Extracellular Nitrite and Nitrate Concentrations in Patients after Aneurysmal Subarachnoid Hemorrhage

Abstract

In a prospective clinical investigation on neurochemical intensive care monitoring, the authors' aim was to elucidate the temporal profile of nitric oxide metabolite concentrations—that is, nitrite and nitrate (NOx)—and compounds related to energy-metabolism in the cerebral interstitium of patients after aneurysmal subarachnoid hemorrhage (SAH). During aneurysm surgery, microdialysis probes were implanted in cerebral white matter of the vascular territory most likely affected by vasospasm. Temporal profiles of NOx were analyzed in a subset of 10 patients (7 female, 3 male, mean age = 47 ± 14 years). Microdialysis was performed for 152 ± 63 hours. Extracellular metabolites (glucose, lactate, pyruvate, glutamate) were recovered from the extracellular fluid of the cerebral parenchyma. NOx was measured using a fluorometric assay. After early surgery, SAH patients revealed characteristic decreases of NOx from initial values of 46.2 ± 34.8 μmol/L to 23.5 ± 9.0 μmol/L on day 7 after SAH ( P < 0.05). Decreases in NOx were seen regardless of development of delayed ischemia (DIND). Overall NOx correlated intraindividually with glucose, lactate, and glutamate ( r = 0.58, P < 0.05; r = 0.32, P < 0.05; r = 0.28, P < 0.05; respectively). After SAH, cerebral extracellular concentrations of NO metabolites decrease over time and are associated with concomitant alterations in energy-or damage-related compounds. This could be related to reduced NO availability, potentially leading to an imbalance of vasodilatory and vasoconstrictive factors. On the basis of the current findings, however, subsequent development of DIND cannot be explained by a lack of vasodilatory NO alone.