title: Cerebrospinal fluid adenosine concentration and uncoupling of cerebral blood flow and oxidative metabolism after severe head injury in humans.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, Safar Center for Resuscitation Research, University of Pittsburgh, Pennsylvania, USA.
authors.forename: R S
authors.initials: RS
authors.lastname: Clark
authors.forename: J A
authors.initials: JA
authors.lastname: Carcillo
authors.forename: P M
authors.initials: PM
authors.lastname: Kochanek
authors.forename: W D
authors.initials: WD
authors.lastname: Obrist
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
authors.forename: Z
authors.initials: Z
authors.lastname: Mi
authors.forename: S R
authors.initials: SR
authors.lastname: Wisneiwski
authors.forename: M J
authors.initials: MJ
authors.lastname: Bell
authors.forename: D W
authors.initials: DW
authors.lastname: Marion
mesh_terms: D000241:Adenosine / Q000134:cerebrospinal fluid*; D000293:Adolescent; D000328:Adult; D001158:Arteries; D002560:Cerebrovascular Circulation / Q000502:physiology*; D002851:Chromatography, High Pressure Liquid; D003128:Coma / Q000209:etiology; D006259:Craniocerebral Trauma / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007601:Jugular Veins; D019344:Lactic Acid / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D010100:Oxygen / Q000097:blood*
chemical_list: D019344:Lactic Acid; D000242:Cyclic AMP; D000241:Adenosine; D010100:Oxygen