Extra‐ and Intracellular pH During Near‐Complete Forebrain Ischemia in the Rat

Abstract

The objective of the present study was to estimate extracellular pH (pH_e) and intracellular pH (pH_i) 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 pH_e and pH_i 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 pH_e 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 · g^0-, 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.