TY - JOUR
T1 - Brain acidosis, cerebral blood flow, capillary bed density, and mitochondrial function in the ischemic penumbra
AU - Anderson, Robert E.
AU - Tan, William K.
AU - Meyer, Fredric B.
N1 - Funding Information:
During focal cerebral ischemia, there is a core region of dense ischemia or evolving infarction surrounded by a borderline region of reduced blood flow. This borderline region of moderate reductions in cerebral blood flow has been termed the ischemic penumbra. 1-3 Within this borderline region, there is a heterogeneous development of From the Thoralf M. Sundt Jr, MD Neurosurgical Research Laboratory, Mayo Clinic and Mayo Graduate School of Medicine, Rochester, MN. Received March 11,1999; accepted May 18,1999. Supported by National Institutes of Health RO1 25374. Address reprint requests to Robert E. Anderson, BS, Department of Neurosurgery, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. Copyright 9 1999 by National Stroke Association
PY - 1999/11
Y1 - 1999/11
N2 - Within the ischemic penumbra, there is a heterogeneous development of cortical intracellular acidosis that is associated with selective neuronal injury. This experiment, which used a rabbit model of moderate focal cerebral ischemia, examined the time course for changes in intracellular brain pH, cortical blood flow, capillary bed density, and mitochondrial function in the ischemic penumbra. After cortical annotation of regions of intracellular acidosis in the ischemic penumbra, the animals underwent transcardiac carbon black perfusion for measurement of capillary bed density. Analysis of variance and Pearson's correlation coefficients were used to determine the relationship between capillary bed density, brain intracellular pH, mitochondrial function, and cortical blood flow. Thirty minutes after the onset of ischemia, cortical blood flow declined from 46±2 to 22±1 mL/100gm/min (P<.01) in all groups. The overall cortical intracellular brain pH measured 6.78±.01 compared with a preischemic value of 6.98±.01 (P<.05). Within this moderately ischemic cortex, there were small regions (1,000 to 45,000 μm2) of increased acidosis, meauring 6.68±.01, not associated with focal changes in cortical blood flow, occurring within 15 minutes of ischemia and persisting throughout the ischemic period. Capillary bed density progressively declined with ongoing ischemia occurring after the development of acidosis. For example, capillary bed density in preischemic controls was 338±6/mm2, whereas after 1 hour of ischemia, it measured 147±12/mm2, at 3 hours 97±23/mm2, and at 6 hours 92±16/mm2. Mitochondrial function was reduced coinciding with the decrease in capillary bed density. These data support the hypothesis that cortical acidosis in the ischemic penumbra facilitates the development of perfusion defects that subsequently lead to mitochondrial dysfunction.
AB - Within the ischemic penumbra, there is a heterogeneous development of cortical intracellular acidosis that is associated with selective neuronal injury. This experiment, which used a rabbit model of moderate focal cerebral ischemia, examined the time course for changes in intracellular brain pH, cortical blood flow, capillary bed density, and mitochondrial function in the ischemic penumbra. After cortical annotation of regions of intracellular acidosis in the ischemic penumbra, the animals underwent transcardiac carbon black perfusion for measurement of capillary bed density. Analysis of variance and Pearson's correlation coefficients were used to determine the relationship between capillary bed density, brain intracellular pH, mitochondrial function, and cortical blood flow. Thirty minutes after the onset of ischemia, cortical blood flow declined from 46±2 to 22±1 mL/100gm/min (P<.01) in all groups. The overall cortical intracellular brain pH measured 6.78±.01 compared with a preischemic value of 6.98±.01 (P<.05). Within this moderately ischemic cortex, there were small regions (1,000 to 45,000 μm2) of increased acidosis, meauring 6.68±.01, not associated with focal changes in cortical blood flow, occurring within 15 minutes of ischemia and persisting throughout the ischemic period. Capillary bed density progressively declined with ongoing ischemia occurring after the development of acidosis. For example, capillary bed density in preischemic controls was 338±6/mm2, whereas after 1 hour of ischemia, it measured 147±12/mm2, at 3 hours 97±23/mm2, and at 6 hours 92±16/mm2. Mitochondrial function was reduced coinciding with the decrease in capillary bed density. These data support the hypothesis that cortical acidosis in the ischemic penumbra facilitates the development of perfusion defects that subsequently lead to mitochondrial dysfunction.
KW - Brain pH
KW - Cortical blood flow
KW - Ischemic penumbra
KW - Perfused capillary density
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U2 - 10.1016/S1052-3057(99)80044-5
DO - 10.1016/S1052-3057(99)80044-5
M3 - Article
C2 - 17895190
AN - SCOPUS:0004035239
SN - 1052-3057
VL - 8
SP - 368
EP - 379
JO - Journal of Stroke and Cerebrovascular Diseases
JF - Journal of Stroke and Cerebrovascular Diseases
IS - 6
ER -