Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra

Robert E. Anderson, William K. Tan, Heidi S. Martin, Fredric B. Meyer

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

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 pH(i), 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 pH(i) 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.

Original languageEnglish (US)
Pages (from-to)160-170
Number of pages11
JournalStroke
Volume30
Issue number1
StatePublished - Jan 1999

Fingerprint

Acidosis
NAD
Infarction
Oxidation-Reduction
Hyperglycemia
Hypoglycemia
Glucose
Brain Ischemia
Regional Blood Flow
Brain
Regeneration
Histology
Ischemia
Fluorescence
Rabbits

Keywords

  • Acidosis
  • Cerebral infarction
  • Cerebral ischemia, focal
  • Glucose
  • Rabbits
  • Redox, NADH

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. / Anderson, Robert E.; Tan, William K.; Martin, Heidi S.; Meyer, Fredric B.

In: Stroke, Vol. 30, No. 1, 01.1999, p. 160-170.

Research output: Contribution to journalArticle

Anderson, Robert E. ; Tan, William K. ; Martin, Heidi S. ; Meyer, Fredric B. / Effects of glucose and PaO2 modulation on cortical intracellular acidosis, NADH redox state, and infarction in the ischemic penumbra. In: Stroke. 1999 ; Vol. 30, No. 1. pp. 160-170.
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abstract = "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 pH(i), 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 pH(i) 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.",
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AU - Meyer, Fredric B.

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N2 - 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 pH(i), 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 pH(i) 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.

AB - 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 pH(i), 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 pH(i) 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.

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KW - Cerebral infarction

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KW - Rabbits

KW - Redox, NADH

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