AJP - Heart and Circulatory Physiology, Vol 272, Issue 6 2557-H2562, Copyright © 1997 by American Physiological Society
Alkalemia reduces recovery from global cerebral ischemia by NMDA receptor-mediated mechanism
P. D. Hurn, R. C. Koehler and R. J. Traystman
Department of Anesthesiology/Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287-4961, USA.
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 (pHi) 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), pHi, 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 pHi was similar among groups, and
pHi 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.
