The effect of acetazolamide on the changes of cerebral blood flow and oxygen metabolism during visual stimulation

Acetazolamide, a carbonic anhydrase inhibitor, has an anticonvulsant effect which may result from a decrease in the efficacy of synaptic transmission due to a decrease of pH. Our previous study showed that acetazolamide induced a significant increase in global and regional cerebral blood flow (CBF), but caused no significant change in the cerebral metabolic rate of oxygen (CMRO(2)). To investigate the effect of acetazolamide on the responses of CBF and CMRO(2) during neural stimulation, we used positron emission tomography to measure CBF and CMRO(2) in six normal volunteers at the fixation-only baseline visual state and during visual stimulation before and after administration of 1 g of acetazolamide. Visual stimulation induced a significant increase in CBF (33%) in the visual cortex compared with baseline values, but caused no significant change in CMRO(2), while no significant change in global CBF or CMRO(2) was found. During visual stimulation after acetazolamide administration, both global and visual cortical CBF and CMRO(2) showed similar changes compared with the respective baseline values (37 and 65% increases in CBF and 8 and 16% decreases in CMRO(2), respectively). When corrected by the global values, the magnitudes of the CBF and CMRO(2) responses to visual stimulation after acetazolamide administration were less than those before (20% vs 38% in CBF and -9% vs 3% in CMRO(2)). Considering our previous observation that the effect of acetazolamide was similar throughout cerebral cortical regions, we suggest that acetazolamide decreases the responses of both CBF and CMRO(2) during visual stimulation, which indicates that this drug may affect neuronal excitability.

[1]  K. Uğurbil,et al.  Effect of Basal Conditions on the Magnitude and Dynamics of the Blood Oxygenation Level-Dependent fMRI Response , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[2]  S. Ogawa Brain magnetic resonance imaging with contrast-dependent oxygenation , 1990 .

[3]  O B Paulson,et al.  Effect of acetazolamide on cerebral blood flow and cerebral metabolic rate for oxygen. , 1984, The Journal of clinical investigation.

[4]  T G Turkington,et al.  Performance characteristics of a whole-body PET scanner. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[5]  M. Moskowitz,et al.  Nitric Oxide Synthase Inhibition and Cerebrovascular Regulation , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[6]  Peter Herscovitch,et al.  Brain blood flow measured with intravenous H/sub 2//sup 15/O. I. Theory and error analysis , 1983 .

[7]  M. Raichle Behind the scenes of functional brain imaging: a historical and physiological perspective. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[8]  G. Glover,et al.  A FAIR Study of Motor Cortex Activation under Normo- and Hypercapnia Induced by Breath Challenge , 1999, NeuroImage.

[9]  F. Hyder,et al.  Total neuroenergetics support localized brain activity: Implications for the interpretation of fMRI , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[10]  M. Raichle,et al.  The effect of acetazolamide on cerebral blood flow and oxygen utilization in the rhesus monkey. , 1978, The Journal of clinical investigation.

[11]  Ravi S. Menon,et al.  Functional brain mapping by blood oxygenation level-dependent contrast magnetic resonance imaging. A comparison of signal characteristics with a biophysical model. , 1993, Biophysical journal.

[12]  F. Hyder,et al.  Stimulated changes in localized cerebral energy consumption under anesthesia. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[13]  J. Meyer,et al.  Interaction of cerebral hemodynamics and metabolism , 1961, Neurology.

[14]  H. Yamauchi,et al.  Effects of Acetazolamide on Cerebral Blood Flow, Blood Volume, and Oxygen Metabolism: A Positron Emission Tomography Study with Healthy Volunteers , 2001, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  I. Tracey,et al.  Prospects for Human Pharmacological Functional Magnetic Resonance Imaging (phMRI) , 2001, Journal of clinical pharmacology.

[16]  R G Shulman,et al.  Cerebral energetics and the glycogen shunt: Neurochemical basis of functional imaging , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[17]  G. Dienel,et al.  Generalized Sensory Stimulation of Conscious Rats Increases Labeling of Oxidative Pathways of Glucose Metabolism When the Brain Glucose–Oxygen Uptake Ratio Rises , 2002, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[18]  Alan C. Evans,et al.  Cerebral [15O]Water Clearance in Humans Determined by PET: I. Theory and Normal Values , 1996, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[19]  F. Plum,et al.  The toxic effects of carbon dioxide and acetazolamide in hepatic encephalopathy. , 1960, The Journal of clinical investigation.

[20]  M. Mintun,et al.  Brain blood flow measured with intravenous H2(15)O. II. Implementation and validation. , 1983, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[21]  Alan C. Evans,et al.  Frequency-Dependent Changes in Cerebral Metabolic Rate of Oxygen during Activation of Human Visual Cortex , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[22]  A. Gjedde,et al.  Model of Blood–Brain Transfer of Oxygen Explains Nonlinear Flow-Metabolism Coupling During Stimulation of Visual Cortex , 2000, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[23]  Jens Frahm,et al.  The Effect of Acetazolamide on Regional Cerebral Blood Oxygenation at Rest and under Stimulation as Assessed by MRI , 1994, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[24]  J. Votaw,et al.  Performance evaluation of the Pico-Count flow-through detector for use in cerebral blood flow PET studies. , 1998, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[25]  M. Raichle,et al.  Focal physiological uncoupling of cerebral blood flow and oxidative metabolism during somatosensory stimulation in human subjects. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[26]  C J Thompson,et al.  Oxygen Consumption of the Living Human Brain Measured after a Single Inhalation of Positron Emitting Oxygen , 1992, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[27]  I. Kanno,et al.  Photic Stimulation Study of Changing the Arterial Partial Pressure Level of Carbon Dioxide , 1995, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[28]  H. Kretschmann,et al.  Neuroanatomy and Cranial Computed Tomography , 1986 .

[29]  M. Mintun,et al.  Nonoxidative glucose consumption during focal physiologic neural activity. , 1988, Science.

[30]  G. Widman,et al.  Carbonic Anhydrase Inhibitor Sulthiame Reduces Intracellular pH and Epileptiform Activity of Hippocampal CA3 Neurons , 2002, Epilepsia.

[31]  H. Fukuyama,et al.  Hemodynamics in internal carotid artery occlusion examined by positron emission tomography. , 1990, Stroke.

[32]  D. Tank,et al.  Brain magnetic resonance imaging with contrast dependent on blood oxygenation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.