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The tolerance of low intracellular pH (pH i ) was examined in vivo in rats by imposing severe, prolonged respiratory acidosis. Rats were intubated and ventilated for 10 min with 20% CO 2 , for 75 min with 50% CO 2 , and for 10 min with 20% CO 2 . The maximum P a co 2  was 320 mm Hg. Cerebral intracellular lactate, pH i , and high-energy phosphate metabolites were monitored in vivo with  31 P and  1 H nuclear magnetic resonance (NMR) spectroscopy, using a 4.7-T horizontal instrument. Within 6 min after the administration of 50% CO 2 , pH i  fell by 0.57 ± 0.03 unit, phosphocreatine decreased by ∼20%, and P i  increased by ∼100%. These values were stable throughout the remainder of the hypercapnic period. Cerebral intracellular lactate, visible with  1 H NMR spectroscopy in the hyperoxic state, decreased during hypercapnia, suggesting either a favorable change in oxygen availability (decreased lactate production) or an increase in lactate clearance or both. All hypercapnic animals awakened and behaved normally after CO 2  was discontinued. Histological examination of cortical and hippocampal areas, prepared using a hematoxylin and eosin stain, showed no areas of necrosis and no glial infiltrates. However, isolated, scattered, dark-staining, shrunken neurons were detected both in control animals (no exposure to hypercapnia) and in animals that had been hypercapnic. This subtle histological change could represent an artifact resulting from imperfect perfusion-fixation, or it could represent subtle neurologic injury during the hypercapnia protocol. In summary, extreme hypercapnia and low pH i  (∼6.5) are well tolerated in rats for periods up to 75 min if adequate oxygenation is maintained. The prolonged stability of metabolite concentrations during hypercapnia makes its use convenient for in vivo animal studies of the relevance of pH i  to brain injury.

Stability of Brain Intracellular Lactate and 3P-Metabolite Levels at Reduced Intracellular pH during Prolonged Hypercapnia in Rats

Stability of Brain Intracellular Lactate and ³P-Metabolite Levels at Reduced Intracellular pH during Prolonged Hypercapnia in Rats