Malignant infarction in cats after prolonged middle cerebral artery occlusion: glutamate elevation related to decrease of cerebral perfusion pressure.
OBJECTIVE
To study the putative role and predictive significance of glutamate elevation in space-occupying ischemic stroke, we investigated the correlation between perfusional disturbances and glutamate alterations in a transient ischemia model in cats that is susceptible to secondary deterioration after reperfusion.


METHODS
In 10 halothane-anesthetized cats, the left middle cerebral artery was occluded for 3 hours, followed by 6 hours of reperfusion. Laser-Doppler flowmetry (LDF) probes, microdialysis/high-performance liquid chromatography, and pressure sensors measured simultaneously regional cerebral blood flow (CBF), extracellular amino acids, mean arterial blood pressure, and intracranial pressure, respectively. Cerebral perfusion pressure (CPP) was calculated. In complementary experiments (n=2), regional CBF was assessed by sequential positron emission tomography.


RESULTS
Middle cerebral artery occlusion reduced LDF-measured CBF in all animals to <25% of control. In 5 of 10 cats, glutamate rose approximately 30-fold during ischemia. LDF-measured CBF and glutamate primarily recovered after reperfusion. Glutamate rose again in the late reperfusion phase, when CPP decreased to <60 mm Hg, and symptoms of transtentorial herniation were recognized. Positron emission tomography revealed ischemic thresholds of 15 to 20 mL/100 g per minute for secondary deterioration. In the other 5 cats, ischemic elevation of glutamate was significantly smaller, and signs of secondary deterioration were not recognized.


CONCLUSIONS
Glutamate determinations during ischemia predict fatal outcome, as do intracranial pressure and CPP measurements during early reperfusion. Secondary amino acid elevation during reperfusion is presumably caused by a drastic decrease of CPP to <50 mm Hg in the final stage of space-occupying, malignant focal ischemia. At this stage, a further progression of injury due to increased glutamate may be irrelevant with respect to fatal outcome.
Toyota
Shingo
S
Max-Planck Institut für neurologische Forschung, Köln, Germany.
Graf
Rudolf
R
Valentino
Mario
M
Yoshimine
Toshiki
T
Heiss
Wolf-Dieter
WD
D000818:Animals; D001783:Blood Flow Velocity; D001794:Blood Pressure; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000503:physiopathology*; D001929:Brain Edema / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology; D002415:Cats; D002544:Cerebral Infarction / Q000000981:diagnostic imaging / Q000209:etiology / Q000503:physiopathology*; D002560:Cerebrovascular Circulation; D004195:Disease Models, Animal; D018450:Disease Progression; D018698:Glutamic Acid / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007427:Intracranial Pressure; D017078:Laser-Doppler Flowmetry; D017551:Microdialysis; D011237:Predictive Value of Tests; D014055:Tomography, Emission-Computed
D018698:Glutamic Acid