Abstract
The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halothane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Um) was used to estimate focal cortical blood flow (CBFu), whereas the ratio of the molecular to the ionic form of the molecule was used to concurrently calculate the local pHi. Resting pHi and flow in normocarbic animals was 7.116 ± 0.008 and 46 ± 8 ml/100 g/min, respectively. Respiratory induced alterations of Paco2 over a range of 20–60 torr revealed a correlated change in pHi from 7.39 ± 0.05 to 7.01 ± 0.03 and a monotonic increase in the rate of Um clearance (slope 0.89 ± 0.13 ml/100 g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid vasodilation (50% dilation = 1–3 s) of pial arterioles and venules and an increase in Um clearance. pHi showed no significant change until around 10 s. The maximum fall in pHi occurred by 30–60 s (6.85 ± 0.054). Longer intervals of stimulation (10 min) resulted in no further decline in pHi, but upon cessation of stimulation, pHi remained acidotic for poststimulation periods up to 10 min, with a mild but statistically significant acidosis being observed at 20 min. The absolute decline in pH observed following stimulation appeared to be closely regulated, as comparable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activation may be considered in three phases: (1) following the onset of activity, an initial acute regulation of pHi at control levels; (2) an intracellular acidosis of around 6.8, which is closely regulated and which can be readily reversed upon termination of stimulation; and (3) during continued stimulation, a change in state where in spite of no further change in pHi, the ability of the cortex to return to control pHi appears to be significantly impaired.