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Notes: Abstract: The objective of the present study was to estimate extracellular pH (pHe) and intracellular pH (pHi) during near-complete forebrain ischemia in the rat, and to evaluate the relative importance of lactic acidosis and rise in tissue Pco2, (Ptco2) in causing pHe and pHi to fall. The animals, which were ventilated, normoxic, normocapnic, and normothermic, were subjected to 15 min of ischemia, either without or with 30–60 min of recirculation. Ptco, was measured with a tissue electrode, pH, with a double-barrel liquid ion-exchanger microelectrode, changes in extracellular fluid (ECF) volume by impedance measurements, tissue CO, content by a microdiffusion technique, and labile tissue metabolites by enzymatic fluorometric methods. Ischemia caused Ptco2 to rise to between 95 and 190 mm Hg (mean 149 mm Hg), and pH, to fall by 0.45–1.05 units (mean 0.70 units). During recovery, Ptco, normalized within 5 min and pHe after 15–30 min. During ischemia, high-energy phosphates were depleted and tissue lactate content increased to 15 μmol · g−1. The total CO2 content (Tco2) was minimally or moderately reduced (normal, 11.9 μmol · g−1; range of ischemic values, 7.9–12.1 μmol · g0-, this range probably reflecting variable amounts of remaining blood flow. Impedance measurements demonstrated that ECF volume during ischemia was reduced to 55% of control, with gradual normalization during the first 15–30 min of recirculation. From values for Ptco2, Tco2, [HCO3−]e, and ECF volume, [HCO3−]i, and pH, could be calculated. These values pertain to an idealized homogeneous intracellular compartment, and the methods used cannot detect whether different intracellular compartments diverge in their acid-base responses. Ischemia caused pH, to fall from 7.05 to a mean of 6.15 (range 5.9–6.4). Previous data, and those obtained at present, suggest that pH, normalizes after 15 min of recirculation, with a subsequent, secondary alkalosis. Calculations indicate that about half of the pH, change was due to the hypercapnia. In intracellular fluid, though, the hypercapnia must play a minor role in reducing pH, the predominate cause of the acidosis being lactic acid production.

Notes: Abstract: The objective of the present study was to assess metabolic changes in the neocortex and hippocampus of well-oxygenated or moderately hypoxic rats in which fluorothyl-induced seizures were sustained for 5 or 20 min, or which were allowed recovery periods of 5, 15, or 45 min following cessation of 20-min seizure activity by withdrawal of the convulsant gas. Sustained fluorothyl-induced seizures were found to cause metabolic alterations qualitatively and quantitatively similar to those previously observed with other commonly used convulsants. Thus, although the phosphorylation state of the adenine nucleotide pool remained only moderately perturbed, if at all, there were decreases in tissue concentrations of phosphocreatine and glycogen, and increases in those of cyclic AMP, lactate, and pyruvate, with a calculated fall in intracellular pH of about 0.15 units and a rise in the cytoplasmic NADH/NAD+ ratio. The enhanced metabolic rate was reflected in a marked reduction in the tissue-to-plasma glucose concentration ratio. Induced moderate hypoxia (arterial Po2 40–50 mm Hg) had no metabolic effect after 5 min of seizures but moderately increased lactate concentrations after 20 min (from about 10 to about 15 μmol ± g−1). On cessation of seizure discharge cyclic AMP and phosphocreatine concentrations normalized already within 5 min, whereas glycogen and lactate concentrations normalized more slowly. In the neocortex (but not the hippocampus) postepileptic tissue-to-plasma glucose concentration ratios rose above control, probably reflecting metabolic depression. The results suggest that intracellular pH promptly returned to control, and that postepileptic alkalosis developed. They also suggest that some elevation of the NADH/NAD+ ratio persisted even after 45 min of recovery.