Changes in extracellular acid-base homeostasis in cerebral ischemia

Abstract

The purpose of this study was to examine the changes in extracellular CO32- and lactate concentration produced by ischemia, especially in relation to the occurrence of anoxic depolarization, and how some of these changes are altered by the inhibition of organic acid transport systems with probenecid. These data demonstrate that (i) the transmembrane mechanisms contributing to intracellular acid-base regulation (Na+/H+ and HCO3-/Cl- exchanges, and lactate/H+ cotransport) are markedly activated during ischemia; (ii) the efficacy of these mechanisms is abolished 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 reuptake with reperfusion, mainly occur via a transporter. These findings imply that residual cellular acid-base homeostasis persists as long as cell depolarization does not occur, and strengthen the concept that anoxic depolarization is a critical event for cell survival during ischemia.