Cerebrospinal fluid adenosine concentration and uncoupling of cerebral blood flow and oxidative metabolism after severe head injury in humans |
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Authors: | RS Clark JA Carcillo PM Kochanek WD Obrist EK Jackson Z Mi SR Wisneiwski MJ Bell DW Marion |
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Affiliation: | Department of Anesthesiology, Safar Center for Resuscitation Research, University of Pittsburgh, Pennsylvania, USA. |
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Abstract: | OBJECTIVE: 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)O2 4 vol%] after head injury. METHODS: 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. RESULTS: CSF adenosine concentration was negatively associated with D(a-v)O2 (P < 0.05, generalized multivariate linear regression model). In addition, CSF adenosine concentration was increased when D(a-v)O2 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 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). CONCLUSION: The association between increased CSF adenosine concentration and a reduction in global cross-brain extraction of oxygen supports a regulatory role for adenosine in the complex balance between CBF and oxidative and nonoxidative metabolism severe head injury in humans. |
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