CEREBROSPINAL-FLUID ADENOSINE CONCENTRATION AND UNCOUPLING OF CEREBRAL BLOOD-FLOW AND OXIDATIVE-METABOLISM AFTER SEVERE HEAD-INJURY IN HUMANS

OBJECTIVE: Uncoupling of cerebral blood flow (CBF) and oxidative metab olism is observed after severe head injury in comatose patients; howev er, the mechanism(s) involved remain undefined. Adenosine can produce cerebral vasodilation and reduce neuronal activity and is a possible m ediator of uncoupling. We hypothesized that cerebrospinal fluid (CSF) adenosine concentrations would be increased during uncoupling of CBF a nd oxidative metabolism, defined as a narrow arterio-jugular venous ox ygen difference [D(a-v)O-2 4 vol%] after head injury. METHODS: Adenosi ne concentrations were measured using fluorescent-based high-pressure liquid chromatography in 67 CSF samples obtained from 13 comatose (Gla sgow Coma Scale score 7) adult patients who sustained a severe closed head injury. At the time each sample was obtained, CBF was measured by the xenon-133 method, and blood samples were obtained for determinati on of D(a-v)O-2. RESULTS: CSF adenosine concentration was negatively a ssociated with D(a-v)O-2 (P < 0.05, generalized multivariate linear re gression model), In addition, CSF adenosine concentration was increase d when D(a-v)O-2 was 4 versus >4 vol% (38.5 [3.2-306.3] versus 14.0 [2 .7-795.5] nmol/L, respectively, median [range]; P < 0.025) and in pati ents who died versus survivors (40.1 [6.9-306.3] versus 12.9 [2.7-795. 5] nmol/L, respectively, median [range]; P < 0.001). CONCLUSION: The a ssociation between increased CSF adenosine concentration and a reducti on in global cross-brain extraction of oxygen supports a regulatory ro le for adenosine in the complex balance between CBF and oxidative and nonoxidative metabolism after severe head injury in humans.