Hypocapnic-hypoglycemic interactions on cerebral high-energy phosphates and pH in dogs

With a level of hypoglycemia (1-1.5 mM) that does not alter cerebral O₂ uptake and glucose uptake in dogs, induction of hypocapnia may cause severe electroencephalographic (EEG) abnormalities. The aim of this study was to determine the effect of hypoglycemia (blood glucose = 1.1 ± 0.1 mM) and hypocapnia (arterial PCO₂ = 15 ± 1 mmHg) on cerebral ATP, phosphocreatine, and intracellular pH (pH(i); ³¹P magnetic resonance spectroscopy), cerebral blood flow (CBF; radiolabeled microspheres), global O₂ uptake, and glucose uptake in anesthetized dogs. Neither hypoglycemia nor hypocapnia alone altered brain high-energy phosphates, pH(i), O₂ or glucose uptake or caused major EEG abnormalities. Hypocapnia alone decreased CBF to 62 ± 4% of control. The combination of hypoglycemia and hypocapnia did not decrease CBF (85 ± 6% of control), and O₂ and glucose uptake were unchanged. During hypocapnic hypoglycemia, isoelectric EEG was seen in 40% of animals, ATP and phosphocreatine decreased to 38 ± 12 and 43 ± 12% of control, respectively, while pH(i) increased from 7.13 ± 0.05 to 7.43 ± 0.09. The increase in pH(i) was related reciprocally to the decrease in venous PCO₂, indicating little change in intracellular bicarbonate concentration ([HCO₃/^-](i)). With normoglycemic hypocapnia, in contrast, estimated [HCO₃/^-](i) decreased 57 ± 1%. These data suggest that active regulation of pH(i) during normoglycemic hypocapnia is impaired during hypoglycemic hypocapnia associated with decreased ATP.