Effect of acetazolamide on rate of CO2 uptake in the perfused rat brain

The accumulation of acid-labile CO2 was measured in the rat brain at early times after exposure to 30% CO2 in oxygen. In particular, the effect on CO2 accumulation of inhibiting brain carbonic anhydrase with acetazolamide was studied. For 57 rats, a rat head perfusion technique was used which permits control and rapid alteration of arterial acid-base conditions. At a paCO2 of 35 mm Hg, total carbon dioxide of the whole brain remained at a normal mean value of 13.4 +/- 0.6 (S.E.) mM/kg during perfusions 209-160 min long. On 30% CO2, brain CO2 increased rapidly to a mean of 24 mM/kg at 5 min and then much more slowly. The latter curve agreed well with values obtained in intact animals. Pretreatment with acetazolamide had no inhibitory effect on CO2 accumulation at 1-5 min. At 5 min, control brain CO2 was 23.9 +/- 0.6 (n = 10) and acetazolamide-pretreated brain CO2 was 24.4 +/- 0.7 (n = 9). Terminal venous pCO2s were 164-180 and 167-172 mm Hg, respectively. Thirty-one unperfused rats were also investigated with similar results. Acetazolamide-pretreated rats had the same CO2 uptake as controls after 15 min exposure to CO2, rather than lower uptake as would be expected if carbonic anhydrase were rate-limiting. The results suggest the need for reinterpretation of some concepts about the role of carbonic anhydrase in CO2 accumulation in the brain.