Alkalemia reduces recovery from global cerebral ischemia by NMDA receptor-mediated mechanism

Patricia D. Hurn, Raymond C. Koehler, Richard J. Traystman

Research output: Contribution to journalArticle

Abstract

In vitro data suggest that low tissue pH reduces, whereas extracellular alkalosis potentiates, cerebral anoxic injury via excitotoxic mechanisms. We tested the hypothesis that in vivo metabolic alkalemia potentiates defects in energy metabolism after global incomplete cerebral ischemia (12 min) and reperfusion (180 min) by an N-methyl-D-aspartate (NMDA) receptor-mediated mechanism. Brain ATP, phosphocreatine, and intracellular pH (pH(i)) were measured by 31P magnetic resonance spectroscopy in anesthetized dogs treated with 1) preischemic intravenous carbicarb buffer (NaHCO3 + Na2CO3, Carb, n = 7); 2) carbicarb infusion plus NMDA receptor antagonist MK-801 (MK- 801 + Carb, n = 7); 3) an osmotically equivalent volume of 5% NaCl (NaCl, n = 8); or 4) equivalent volume of 0.9% NaCl (Sal, n = 3). Sagittal sinus pH was raised to 7.82 ± 0.04 before and 7.65 ± 0.03 during ischemia in Carb vs. 7.72 ± 0.01 and 7.60 ± 0.01 in MK-801 + Carb, 7.25 ± 0.02 and 7.15 ± 0.03 in NaCl, and 7.31 ± 0.00 and 7.26 ± 0.01 in Sal, respectively. Ischemic cerebral blood flow (CBF, radiolabeled microspheres), ph(i), and ATP reduction were similar among groups. By 180 min of reperfusion, recovery of ATP was greater in MK-801 + Carb (104 ± 6% of baseline), NaCl (93 ± 6%), and Sal (94 ± 6%) than in Carb (47 ± 6%). Intraischemic pH(i) was similar among groups, and pH(i) recovery did not vary among groups despite differences in sagittal sinus pH. In Carb, CBF was restored but with delayed hypoperfusion. We conclude that extracellular alkalosis is deleterious to postischemic CBF and energy metabolism, acting by NMDA receptor-mediated mechanisms.

Original languageEnglish (US)
Pages (from-to)H2557-H2562
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume272
Issue number6 41-6
StatePublished - Jul 30 1997

Keywords

  • Carbicarb
  • Magnetic resonance spectroscopy
  • N-methyl-D-aspartate

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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