ALKALEMIA REDUCES RECOVERY FROM GLOBAL CEREBRAL-ISCHEMIA BY NMDA RECEPTOR-MEDIATED MECHANISM

In vitro data suggest that low tissue pH reduces, whereas extracellula r alkalosis potentiates, cerebral anoxic injury via excitotoxic mechan isms. We tested the hypothesis that in vivo metabolic alkalemia potent iates defects in energy metabolism after global incomplete cerebral is chemia (12 min) and reperfusion (180 min) by an N-methyl-D-aspartate ( NMDA) receptor-mediated mechanism. Brain ATP, phosphocreatine, and int racellular pH (pH(i)) were measured by P-31 magnetic resonance spectro scopy in anesthetized dogs treated with 1) preischemic intravenous car bicarb buffer (NaHCO3 + Na2CO3, Carb, n = 7); 2) carbicarb infusion pl us NMDA receptor antagonist MK-801 (MK-801 + Carb, n = 7); 3) an osmot ically equivalent volume of 5% NaCl (NaCl, n = 8); or 4) equivalent vo lume 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. 1.72 +/- 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%). Int raischemic pill was similar among groups, and pH(i) recovery did not v ary among groups despite differences in sagittal sinus pH. In Carb, CB F was restored but with delayed hypoperfusion. We conclude that extrac ellular alkalosis is deleterious to postischemic CBF and energy metabo lism, acting by NMDA receptor-mediated mechanisms.