title: Cerebral vasoreactivity assessed with transcranial Doppler and regional cerebral blood flow measurements. Dose, serum concentration, and time course of the response to acetazolamide.
abstract: OBJECTIVE
  To improve the assessment of cerebral vasoreactivity using acetazolamide (ACZ), we studied the time course of the response and the relationship between dose, response, and serum concentration.
  
  
  METHODS
  Blood flow velocities were measured with the use of transcranial Doppler ultrasonography in one of the middle cerebral arteries of 48 healthy subjects after the intravenous administration of 1 to 1.6 g ACZ. In 34 subjects (group 1), velocities were measured every second minute to detect the maximum middle cerebral artery velocity increase. We also measured regional cerebral blood flow using single-photon emission computed tomography in 27 of the subjects in group 1 before and approximately 15 to 20 minutes after the ACZ injection. The serum concentration of ACZ was measured in 15 subjects. In the remaining 14 subjects (group 2), middle cerebral artery velocity measurements were made 10, 25, 30, and 45 minutes after ACZ administration to obtain information regarding the late time course of the response.
  
  
  RESULTS
  In group 1 the plateau phase of the velocity response was reached 8 to 15 minutes after ACZ administration. A large range of velocity increase was observed, and a significant correlation was found between the maximum velocity increase and the dose and serum concentration of ACZ. In group 2 subjects, maximum velocities were maintained 30 minutes after the injection, but after 45 minutes velocities had decreased to 68% of their highest level. No significant relationship was found between dose or serum concentration of ACZ and the regional cerebral blood flow increase. The velocity increase after ACZ was similar in both older and younger subjects.
  
  
  CONCLUSIONS
  This study shows that cerebral vasoreactivity is best assessed 10 to 30 minutes after ACZ administration and that the dose should probably exceed 15 mg/kg if a maximum vasodilatory response in the cerebral circulation is to be obtained.
mesh_terms: D000086:Acetazolamide / Q000493:pharmacokinetics / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D001783:Blood Flow Velocity / Q000187:drug effects; D002257:Carbonic Anhydrase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D017585:Ultrasonography, Doppler, Transcranial
chemical_list: D002257:Carbonic Anhydrase Inhibitors; D000086:Acetazolamide