Alkalemia reduces recovery from global cerebral ischemia by nmda
receptor-mediated mechanism.
Hurn, Patricia D., Raymond C. Koehler, and Richard J. Traystman.
Department of Anesthesiology/Critical Care Medicine, The Johns
Hopkins Medical Institutions. Baltimore, MD 21287-4961
APStracts 3:0538H, 1996.
In vitro data suggest that low tissue pH reduces, while 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 a NMDA
receptor-mediated mechanism. Brain ATP, phosphocreatine and
intracellular pH (pHi) were measured by 31P magnetic resonance
spectroscopy in anesthetized dogs treated with either: 1) pre
-ischemic intravenous Carbicarb buffer (NaHCO3 +Na2CO3, CARB, n=7); 2)
Carbicarb infusion plus NMDA receptor antagonist MK801 (MK801+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 MK801+CARB, 7.25+0.02 and 7.15+0.03 in
NaCl, and 7.31+0.00 and 7.26+0.01 in SAL. Ischemic cerebral blood
flow (CBF, radiolabelled microspheres), pHi, and ATP reduction were
similar among groups. By 180 min of reperfusion, recovery of ATP was
greater in MK801+CARB (104+6% of baseline), NaCl (93+6%), and SAL
(94+6%) than in CARB (47+6%). Intra-ischemic pHi was similar among
groups, and pHi recovery did not vary among groups in spite of
differences in sagittal sinus pH. In CARB, CBF was restored but with
delayed hypoperfusion. We conclude that extracellular alkalosis is
deleterious to post-ischemic CBF and energy metabolism, acting by
NMDA-receptor mediated mechanisms.
Received 24 September 1996; accepted in final form 6 December
1996.
APS Manuscript Number H859-6.
Article publication pending Am. J. Physiol. (Heart Circ. Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996