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The Journal of Neuroscience, July 1, 1999, 19(13):5506-5513
Brain Mechanisms of Propofol-Induced Loss of Consciousness in
Humans: a Positron Emission Tomographic Study
Pierre
Fiset1, 3,
Tomás
Paus2,
Thierry
Daloze1,
Gilles
Plourde1,
Pascal
Meuret1,
Vincent
Bonhomme1,
Nadine
Hajj-Ali4,
Steven B.
Backman1, 3, and
Alan C.
Evans2
Departments of 1 Anesthesiology and
2 Neurology and Neurosurgery and 3 McGill
University Health Center, McGill University, Montreal, Quebec, Canada,
H3A 1A1, and 4 Faculté de Pharmacie, Université
de Montréal, Montreal, Quebec, Canada H3C 3J7
In the present study, we used positron emission tomography to
investigate changes in regional cerebral blood flow (rCBF) during a
general anesthetic infusion set to produce a gradual transition from
the awake state to unconsciousness. Five right-handed human volunteers
participated in the study. They were given propofol with a
computer-controlled infusion pump to achieve three stable levels of
plasma concentrations corresponding to mild sedation, deep sedation,
and unconsciousness, the latter defined as unresponsiveness to verbal
commands. During awake baseline and each of the three levels of
sedation, two scans were acquired after injection of an
H215O bolus. Global as well as regional
CBF were determined and correlated with propofol concentrations. In
addition, blood flow changes in the thalamus were correlated with those
of the entire scanned volume to determine areas of coordinated changes.
In addition to a generalized decrease in global CBF, large regional
decreases in CBF occurred bilaterally in the medial thalamus, the
cuneus and precuneus, and the posterior cingulate, orbitofrontal, and
right angular gyri. Furthermore, a significant covariation between the
thalamic and midbrain blood flow changes was observed, suggesting a
close functional relationship between the two structures.
We suggest that, at the concentrations attained, propofol
preferentially decreases rCBF in brain regions previously implicated in
the regulation of arousal, performance of associative functions, and
autonomic control. Our data support the hypothesis that anesthetics induce behavioral changes via a preferential, concentration-dependent effect on specific neuronal networks rather than through a nonspecific, generalized effect on the brain.
Key words:
anesthesia; PET; arousal; consciousness; thalamus; reticular formation; cerebral blood flow; propofol
Copyright © 1999 Society for Neuroscience 0270-6474/99/19135506-08$05.00/0
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