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(Stroke. 1997;28:2045-2052.)
© 1997 American Heart Association, Inc.
Articles |
Early Detection of Irreversibly Damaged Ischemic Tissue by Flumazenil Positron Emission Tomography in Cats
From the Max-Planck-Institut für neurologische Forschung, Köln, Germany.
Correspondence to W.-D. Heiss, MD, Max-Planck-Institut für neurologische Forschung, Gleueler Str 50, D-50931 Köln, Germany.
Background and Purpose Ligands for cerebral benzodiazepine receptors were used in the past to indicate the intactness of cortical neurons in subacute to chronic states after stroke and thus to differentiate among brain regions with complete or incomplete infarction and with functional deactivation. For planning acute interventional therapy, however, a marker of irreversible damage in early ischemia is needed. We studied the applicability of [11C]flumazenil (FMZ) for differentiation between tissue with and without potential of recovery in the first hours after focal experimental ischemia.
Methods In 11 cats, cerebral blood flow, cerebral
metabolic rate for oxygen, oxygen extraction fraction, and
FMZ binding were studied repeatedly by positron emission tomography
before, during, and up to 12 hours after transient middle cerebral
artery occlusion (MCAO) (30 minutes in 2, 60 minutes in 7, and 120
minutes in 2 cats, respectively). Development of the defects in energy
metabolism were compared with the defects in FMZ binding (2
to 3 hours and 8 to 9 hours after MCAO), with the pattern of disturbed
glucose metabolism (determined 12 hours after MCAO), and
with the size of the infarcts (determined 
15 hours after MCAO).
Results Irrespective of the level of reperfusion, defects in FMZ binding (2 to 3 hours after MCAO) were closely related to areas with severely depressed oxygen consumption and predicted the size of the final infarcts, whereas preserved FMZ binding indicated intact cortex. Depression of glucose metabolism was in all animals larger than the defects in FMZ binding and the infarcts, indicating functional deactivation of brain areas beyond the permanent morphological damage. In addition, FMZ distribution within 2 minutes after injection was significantly correlated to flow and yielded reliable perfusion images.
Conclusions The reduction of FMZ binding early after focal ischemia reflects irreversible neuronal damage that otherwise only can be detected by multitracer studies. Our experimental data and first clinical applications suggest that FMZ has potential as an indicator of developing infarction. Since FMZ distribution additionally images perfusion, this tracer might be useful for the selection of patients who would benefit from acute therapeutic intervention.
Key Words: cerebral blood flow • cerebral ischemia, focal • flumazenil • neuronal damage • positron emission tomography • receptors, benzodiazepine • cats
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