Effect of superhypercapnia on cortical pH(i) and cortical blood flow

In vivo panoramic imaging of regional cortical blood flow and intracellular brain pH with umbelliferone fluorescence was performed in fasted New Zealand White rabbits (n = 30) subjected to constant or stepwise increases in arterial PCO₂ (Pa(CO₂)) up to 160 mmHg under 1.0% halothane anesthesia. At a Pa(CO₂) of 40 mmHg, baseline brain pH(i) measured 7.03 ± 0.04, while regional cortical blood flow was 47.0 ± 4.3 ml · 100 g^-1 · min^-1. With an immediate but constant exposure to a Pa(CO₂) of 60, 80, or 120 mmHg, at 15 min pH(i) fell to 6.94 ± 0.03, 6.89 ± 0.03, and 6.90 ± 0.03 and recovered over 20, 80, and 120 min, respectively. At 160 mmHg Pa(CO₂), pH(i) fell to 6.68 ± 0.04 and remained acidotic. With stepwise increases in Pa(CO₂) up to 80 mmHg, brain pH(i) decreased from 7.01 ± 0.02 to 6.99 ± 0.02, not significantly different despite a severe systemic acidosis of 7.022 ± 0.034. At a Pa(CO₂) of 120 and 160 mmHg, pH(i) dropped to 6.97 ± 0.02 and 6.93 ± 0.02, respectively. The difference in brain pH(i) between an immediate and stepwise exposure to a Pa(CO₂) of 160 mmHg was significant (P < 0.005). These results demonstrate that brain pH(i) is tightly regulated across the cortical surface and resistant to profound changes in extracellular pH. The difference in pH(i) between the constant and incremental increases in Pa(CO₂) suggests that there is upregulation of pH homeostatic mechanisms.