title: Effects of early and late intravenous norepinephrine infusion on cerebral perfusion, microcirculation, brain-tissue oxygenation, and edema formation in brain-injured rats.
abstract: OBJECTIVE
  Reduction of cerebral perfusion during the early phase after traumatic brain injury is followed by a later phase of normal to increased perfusion. Thus, pharmacologically elevating mean arterial blood pressure with the aim of improving cerebral perfusion may exert different time-dependent effects on cortical perfusion, microcirculation, tissue oxygenation and brain edema formation after traumatic brain injury.
  
  
  METHODS
  Randomized, placebo-controlled trial.
  
  
  METHODS
  Experimental laboratory at a university hospital.
  
  
  METHODS
  A total of 37 male Sprague-Dawley rats subjected to a focal cortical contusion.
  
  
  METHODS
  At 4 or 24 hrs after focal traumatic brain injury, mean arterial blood pressure was increased to 120 mm Hg for 90 mins by infusing norepinephrine. In rats receiving physiologic saline, mean arterial blood pressure remained unchanged. In the first series, pericontusional cortical perfusion was measured using the laser Doppler flowmetry scanning technique before injury and before, during, and after the infusion period. In a second series, intracranial and cerebral perfusion pressure and intraparenchymal perfusion and tissue oxygen measured within the contused and pericontusional cortex were recorded continuously before, during, and after norepinephrine infusion. Changes in cortical microcirculation were investigated by orthogonal polarization spectral imaging. At the end of each experiment, hemispheric swelling and water content were determined gravimetrically.
  
  
  RESULTS
  At 4 and 24 hrs after traumatic brain injury, intravenous norepinephrine significantly increased pericontusional cortical perfusion, which was also reflected by an increase in diameters and flow velocities of pericontusional arterioles and venules. Cerebral perfusion pressure and intraparenchymal perfusion and tissue oxygen were significantly increased during norepinephrine infusion at 4 and 24 hrs. Hemispheric swelling and water content showed no difference between the groups.
  
  
  CONCLUSIONS
  After cortical impact injury, early and late intravenous norepinephrine infusion pressure-dependently increased cerebral perfusion and tissue oxygenation without aggravating or reducing brain edema formation. Future studies are warranted to determine long-term changes of short and prolonged norepinephrine-induced increases in mean arterial blood pressure and cerebral perfusion pressure.
authors.affiliation: Department of Neurosurgery, Charité, Virchow Medical Center, Humboldt University, Berlin, Germany.
authors.forename: Stefan-Nikolaus
authors.initials: SN
authors.lastname: Kroppenstedt
authors.forename: Ulrich-Wilhelm
authors.initials: UW
authors.lastname: Thomale
authors.forename: Martin
authors.initials: M
authors.lastname: Griebenow
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Sakowitz
authors.forename: Klaus-Dieter
authors.initials: KD
authors.lastname: Schaser
authors.forename: Petra S
authors.initials: PS
authors.lastname: Mayr
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Unterberg
authors.forename: John F
authors.initials: JF
authors.lastname: Stover
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001786:Blood Glucose; D001929:Brain Edema / Q000378:metabolism*; D001930:Brain Injuries / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply* / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007262:Infusions, Intravenous; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009638:Norepinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D001786:Blood Glucose; D014662:Vasoconstrictor Agents; D009638:Norepinephrine