Response of the human brain to a hypercapnic acid load in vivo.

1. The aim of this investigation was to measure the change in intracellular pH of human brain in vivo in response to hypercapnia. 2. Five healthy male subjects inspired air for 20 min and then 5% CO2/95% O2 for 30 min, of which the first 10 min was used to achieve a steady-state end-tidal CO2 measurement. 3. 31P nuclear magnetic resonance spectroscopy was used to measure intracellular pH while breathing air and during hypercapnia. Simultaneous localization between superficial and deep brain was achieved by using the phase-modulated rotating frame imaging technique. One subject volunteered to breath air for a further phase-modulated rotating frame imaging study while recovering from hypercapnia. 4. End-tidal CO2 increased when breathing 5% CO2/95% O2 (on air, 5.57 +/- 0.21%; on 5% CO2/95% O2, 6.41 +/- 0.16%; rise = +0.84 +/- 0.09%; means +/- SEM) causing a reduction in brain intracellular pH, which was more pronounced in deep brain (5 cm = mainly white matter, from 7.02 +/- 0.006 pH units to 6.96 +/- 0.001 pH units, mean +/- SEM) than in superficial brain (2 cm = mainly grey matter, from 7.02 +/- 0.006 pH units to 7.00 +/- 0.006 pH units, mean +/- SEM). 5. The white matter responded to hypercapnia with a greater fall in intracellular pH than the grey matter. This could either be due to differences in blood flow between grey and white matter in response to hypercapnia or to differences in intracellular pH regulation/buffering between these two tissues.