Summary:The time course of changes in cortical tissue pH (pHi) and blood flow during cortical seizures in halo thane-anesthetized cats was examined. The clearance of the molecular form of umbelliferone (Urn) 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/IOO glmin, respectively. Respiratory in duced alterations of PaC02 over a range of 20-60 torr re vealed a correlated change in pHi from 7.39 ± 0.05 to 7.01 ± 0. 03 and a monotonic increase in the rate of Urn clearance (slope 0.89 ± 0.13 mllIOO g/min/torr). Focal electrical stimulation of the cortex resulted in a rapid va sodilation (50% dilation = 1-3 s) of pial arterioles and venules and an increase in Urn clearance. pHi showed no significant change until around \0 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 Intracellular pH (pHi) reflects the equilibrium be tween the generation of acidic (notably lactic acid and a variety of lipidic acids) and alkaloidic (such as NH 3 ) products of cellular metabolism (Siesj6, 1984) and the processes that counter their pres ence, including the passive buffering capacity of the cell (e. g., diffusion, chemical buffering, utilization of H+ in enzymatic reaction) (Siesj6 and Messeter. 1971) and the processes of active extrusion (e. g .. H+ IHC0 3 -, H + INa + exchange systems) (Roos and Boron, 1981; Fencl, 1986). Changes in brain pHi will become apparent only if the generation of Abbreviations used: CBFu, focal cortical blood flow; pH e, ex tracellular pH ; pH i, intracellular pH ; Ui, ionized umbelliferone; Urn, molecular umbelliferone.
332pHi, but upon cessation of stimulation, pHi remained acidotic for post stimulation periods up to \0 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 compa rable levels following stimulation were observed during hypocarbia and hypercarbia. These observations thus suggest that pHi regulation during intense cortical activa tion may be considered in three phases: (1) following the onset of activity, an initial acute regulation of pHi at con trol levels; (2) an intracellular acidosis of around 6.8, which is closely regulated and which can be readily re versed 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 re turn to control pHi appears to be significantly impaired.