CHANGES IN EXTRACELLULAR ACID-BASE HOMEOSTASIS IN CEREBRAL-ISCHEMIA

The purpose of this study was to examine the changes in extracellular CO32- and lactate concentration produced by ischemia, especially in re lation to the occurrence of anoxic depolarization, and how some of the se changes are altered by the inhibition of organic acid transport sys tems with probenecid. These data demonstrate that (i) the transmembran e mechanisms contributing to intracellular acid-base regulation (Na+/H + and HCO3-/Cl- exchanges, and lactate/H+ cotransport) are markedly ac tivated during ischemia; (ii) the efficacy of these mechanisms is abol ished as the cellular membrane permeability to ions, including H+ and pH-changing anions, suddenly increases with anoxic depolarization; and (iii) efflux of intracellular lactate during ischemia, and its reupta ke with reperfusion, mainly occur via a transporter. These findings im ply that residual cellular acid-base homeostasis persists as long as c ell depolarization does not occur, and strengthen the concept that ano xic depolarization is a critical event for cell survival during ischem ia.