In vivo Studies on Intracellular pH, Focal Flow, and Vessel Diameter in the Cat Cerebral Cortex: Effects of Altered CO₂ and Electrical Stimulation

Abstract

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.

Increased pH and Seizure Foci Inorganic Phosphate in Temporal Demonstrated by [31P]MRS

“…The changes of pH and Pi found in the epileptogenic temporal lobe could represent altered metdbolism caused by repeated seizures. In animal models, the high rate of energy expenditure has been repeatedly shown to be associated with seizures causes depletion of PCr and ATP, and increases of Pi, lactate, and H + (Young et al, 1985;Younkin et al, 1986;Yaksh and Anderson, 1987;Schnall et al, 1988). During seizures in cats, Yaksh and Anderson (1987) demonstrated a dramatic decrease in pH from 7.11 to 6.85, and the brain tissue remained acidotic for >20 min.…”

Mechanisms of Cerebrovascular O2 Sensitivity from Hyperoxia to Moderate Hypoxia in the Rat

“…In their study, however, while the measurements of brain tissue K + and P02 may be reliable, the pH electrodes with tip diameters of tOO f.Lm probably caused excessive tissue destruction, resulting in loss of autoregula tion and unacceptably high pH values of 7.3 to 7.4. Measurements made with microelectrodes with tip diameters of 1-5 f.Lm (Nemoto and Frinak, 1981;von Ardenne and Reitnauer, 1970;Urbanics et aI., 1978), 5,5-dimethyloxazolidine-2,4, dione (DMO) (Roos, 1971), and indicator (Sundt and Anderson, 1980;Yaksh and Anderson, 1987) have all reported values during normoxia of about 7.0 to 7.1. It is not surprising that traumatized brain responds to hyp oxia with a transient alkalosis due to the hyperper fusion that occurs with the increase in arterial blood pressure at the initiation of the hypoxia.…”

Preferential intracellular pH regulation: hypotheses and perspectives

“…Further support for this conclusion is the substantial evidence that mammals subjected to an acute respiratory acidosis display coupled pH regulation. Adult dog (Arieff et al, 1976) and cat (Yaksh and Anderson, 1987) pH e and pH i were reduced following exposure to ≥8 kPa P CO2 for 3 h and 10 min, respectively. In guinea pigs exposed to 15 kPa P CO2 , there was an uncompensated reduction in pH e and pH i of lung, kidney, heart and muscle between 2 and 8 h of exposure, but at 7 days, pH e and pH i exhibited compensation of 68% and 80-106%, respectively; a response indicative of coupled pH regulation (Wood and Schaefer, 1978).…”

“…Respiratory acidoses occur as a result of an increase in blood CO 2 , either from the environment (hypercarbia; see Glossary) or by retention of metabolically produced CO 2 (hypercapnia; see Glossary); typical arterial values of partial pressure of CO (P CO2 ) for adult water-breathing and bimodally breathing fishes, and reptiles and mammals are 0.1-0.5 (Ultsch, 1996), 0.5-3.5 Brauner, 2014), 1.8-4.3 (Ultsch, 1996) and 4.5-5.6 kPa P CO2 (Arieff et al, 1976;Malan et al, 1985;Wood and Schaefer, 1978;Yaksh and Anderson, 1987), respectively. Any increase in P CO2 beyond those values shifts the equilibrium of the CO 2 hydration reaction (CO 2 +H 2 O↔H + +HCO 3 − ), promoting the formation of H + and HCO 3 − and lowering pH, resulting in acidosis.…”