(Stroke. 1999;30:160-170.)
© 1999 American Heart Association, Inc.
Original Contributions |
Effects of Glucose and PaO2 Modulation on Cortical Intracellular Acidosis, NADH Redox State, and Infarction in the Ischemic Penumbra
From the Thoralf M. Sundt, Jr, Neurosurgical Research Laboratory, Mayo Clinic and Mayo Graduate School of Medicine, Rochester, Minn.
Background and Purpose—During focal cerebral ischemia, the ischemic penumbra or border-zone regions of moderate cortical blood flow reductions have a heterogeneous development of intracellular cortical acidosis. This experiment tested the hypotheses that (1) this acidosis is secondary to glucose utilization and (2) this intracellular acidosis leads to recruitment of potentially salvageable tissue into infarction.
Methods—Brain pHi, regional cortical blood flow, and
NADH redox state were measured by in vivo fluorescent imaging,
and infarct volume was assessed by
triphenyltetrazolium chloride histology.
Thirty fasted rabbits divided into 6 groups of 5 each were subjected to
4 hours of permanent focal ischemia in the presence of
hypoglycemia (
2.8 mmol/L), moderate hyperglycemia (11
mmol/L), and severe hyperglycemia (>28 mmol/L) under either
normoxia or moderate hypoxia (PaO2
50 mm Hg).
Results—Preischemic hyperglycemia led to a more pronounced intracellular acidosis and retardation of NADH regeneration than in the hypoglycemia groups under both normoxia and moderate hypoxia in the ischemic penumbra. For example, 4 hours after ischemia, brain pHi in the severe hyperglycemia/normoxia group measured 6.46, compared with 6.84 in the hypoglycemia/normoxia group (P<0.01), and NADH fluorescence measured 173% compared with 114%. Infarct volume in the severe hyperglycemia/normoxia group measured 35.1±6.9% of total hemispheric volume, compared with 13.5±4.2% in the hypoglycemia/normoxia group (P<0.01).
Conclusions—Hyperglycemia significantly worsened both cortical intracellular brain acidosis and mitochondrial function in the ischemic penumbra. This supports the hypothesis that the evolution of acidosis in the ischemic penumbra is related to glucose utilization. Furthermore, the observation that hypoglycemia significantly decreased infarct size supports the postulate that cortical acidosis leads to recruitment of ischemic penumbra into infarction.
Editorial Comment
Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland
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