Cerebrospinal Fluid Adenosine Concentration and Uncoupling of Cerebral Blood Flow and Oxidative Metabolism after Severe Head Injury in Humans

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Abstract
Uncoupling of cerebral blood flow (CBF) and oxidative metabolism is observed after severe head injury in comatose patients; however, the mechanism(s) involved remain undefined. Adenosine can produce cerebral vasodilation and reduce neuronal activity and is a possible mediator of uncoupling. We hypothesized that cerebrospinal fluid (CSF) adenosine concentrations would be increased during uncoupling of CBF and oxidative metabolism, defined as a narrow arterio-jugular venous oxygen difference [D (a - v)02 4 vol%] after head injury. Adenosine concentrations were measured using fluorescent-based high-pressure liquid chromatography in 67 CSF samples obtained from 13 comatose (Glasgow 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 determination of D (a-v)O2. CSF adenosine concentration was negatively associated with D (a - v)02 (P 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 patients 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). The association between increased CSF adenosine concentration and a reduction in global crossbrain extraction of oxygen supports a regulatory role for adenosine in the complex balance between CBF and oxidative and nonoxidative metabolism after severe head injury in humans.