Summary:The objective of the present study was to discover whether or not intracellular alkalosis develops in the brain in the recovery period following transient ischemia, Forebrain ischemia of IS-min duration was in duced by four-vessel occlusion in rats, with recovery periods of IS, 60, and 180 min. Intracellular pH was derived both by the HC03--H2C03 method and from the creatine kinase equilibrium. The ischemia was associated with energy failure and marked accumulation of lactic acid in the cerebral cortex. Recirculation brought about rapid rephosphorylation of adenine nucleotides and graIt has been repeatedly observed that metabolic re covery following a period of transient brain ischemia often includes an increase above control levels of the phosphocreatine/creatine ratio (Ljunggren et a!., 1974a;Marshall et a!., 1975;Levy and Duffy, 1977; Nordstrom et a!., 1978a,b;Rehncrona et a!., 1981). Theoretically, such an increase may reflect either a change in the equilibrium constant of the creatine kinase (CK) reaction, e.g., due to an altered intracellular Mg 2 + concentration, or it may be due to intracellular alkalosis (see Ljunggren et al., 197 4a, b; Nordstrom et al., 1978a). The latter possibility de rives from the fact that the equilibrium of the CK re action is pH-dependent and that the reaction may, therefore, be used to estimate changes in intraceIIu lar pH (Kuby and Noltmann, 1962;Rose, 1968). This assumption was substantiated by experiments in which changes in intracellular pH (pHi) in the brain Dr. Mabe is on leave of absence from Department of Neurosurgery, Nagoya City University, Nagoya, Japan.Address correspondence and reprint requests to Professor Siesjo at Laboratory for Brain Research, Floor EA-5, Lund Hospital, S-221 85 Lund, Sweden.Abbreviations used: CK, Creatine kinase; Cr, creatine; ECF, extracellular fluid; PCr, phosphocreatine; pH;, intracellular pH; PtCOz, tissue CO2 tension.
109dual normalization of lactic acid levels. After 15 min of recovery, the HC03 --H2C03 method indicated per sisting acidosis, but the creatine kinase reaction did not. After 60 min, a shift of pH in the alkaline direction was demonstrated in both methods. This alkalosis had dis appeared after 3 h of recovery. It is concluded that re sumption of ATP production after ischemia is followed by a rapid rise in intracellular pH, which transiently in creases above normal.