TY - JOUR
T1 - Alkalemia reduces recovery from global cerebral ischemia by NMDA receptor-mediated mechanism
AU - Hurn, Patricia D.
AU - Koehler, Raymond C.
AU - Traystman, Richard J.
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
KW - Carbicarb
KW - Magnetic resonance spectroscopy
KW - N-methyl-D-aspartate
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U2 - 10.1152/ajpheart.1997.272.6.h2557
DO - 10.1152/ajpheart.1997.272.6.h2557
M3 - Article
C2 - 9227531
AN - SCOPUS:33751263661
SN - 0363-6135
VL - 272
SP - H2557-H2562
JO - American Journal of Physiology - Heart and Circulatory Physiology
JF - American Journal of Physiology - Heart and Circulatory Physiology
IS - 6 41-6
ER -