title: Norepinephrine-induced hyperglycemia does not increase cortical lactate in brain-injured rats.
abstract: OBJECTIVE
  Hyperglycemia aggravates ischemic brain damage. Since catecholamines increase hepatic gluconeogenesis, resulting in hyperglycemia, we investigated whether norepinephrine and dopamine elevate arterial blood glucose, thereby increasing pericontusional cortical glucose and lactate concentrations and brain edema in brain-injured rats.
  
  
  METHODS
  Prospective, randomized, controlled animal study.
  
  
  METHODS
  Male Sprague Dawley rats.
  
  
  METHODS
  Physiological saline solution, norepinephrine, or dopamine were infused intravenously for 90 min beginning 4.5 h after inducing a focal cortical contusion. Blood glucose, lactate, and pericontusional cortical extracellular glucose and lactate were determined before, during and up to 60 min after the infusion period. Thereafter brains were removed to assess hemispheric water content.
  
  
  RESULTS
  Continuous norepinephrine and dopamine infusion significantly increased pericontusional glucose concentrations, being mostly sustained by norepinephrine (NaCl: 1.3+/-0.2, dopamine: 2.7+/-0.2, norepinephrine: 4.8+/-1.1 mM). While arterial blood glucose was only significantly elevated in norepinephrine-treated rats from 8.6+/-0.6 to 12.6+/-1.6 mM, the extracellular to blood glucose ratio was significantly increased in dopamine- and norepinephrine-treated rats (0.28+/-0.01 and 0.38+/-0.05 vs. 0.17+/-0.01). Plasma and pericontusional lactate remained unchanged, and brain edema was similar in all groups.
  
  
  CONCLUSIONS
  Norepinephrine and dopamine significantly increased pericontusional glucose concentrations which did not elevate extracellular lactate and aggravate underlying posttraumatic edema formation. In addition to possibly increased facilitated endothelial glucose transport, the elevated extracellular to blood glucose ratio suggests a passive concentration- and pressure- dependent entry via a damaged blood-brain barrier. This might contribute to the observed reversible increase in extracellular glucose.
authors.affiliation: Department of Neurosurgery, Charité, Virchow Medical Center, Humboldt University Berlin, Germany. stover@mail.med.upenn.edu
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Sakowitz
authors.forename: Ulrich W
authors.initials: UW
authors.lastname: Thomale
authors.forename: Stefan N
authors.initials: SN
authors.lastname: Kroppenstedt
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Unterberg
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D006943:Hyperglycemia / Q000139:chemically induced*; D007773:Lactates / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000008:administration & dosage / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D007773:Lactates; D009638:Norepinephrine