The Deleterious Effect of Excessive Tissue Lactic Acidosis in Brain Ischemia

Abstract

The understanding of the basic series of events leading to brain cell damage and failure of postischemic neurological recovery is essential for the possibilities of taking adequate measures for brain protection in patients that run the risk of critical cerebral ischemia. Although extensively studied both clinically and experimentally (for literature see Siesjö, 1978; Rehncrona and Siesjö, 1981), the exact knowledge of those biochemical mechanisms that are directly responsible for the development of irreversible injury is relatively meagre. A mild to moderate decrease in tissue oxygen supply induces functional changes that are unrelated to any detectable deterioration of the cerebral energy state and most probably represent reversible changes in intercellular transmission. The more severe insults, leading to irreversible damage and cell death, have in common that energy production fails to keep pace with tissue energy demands, which results in a fast depletion of energy stores and energy failure. As a consequence of the lack of available energy (in the form of ATP) for the ionic pumps, ionic homeostasis is disrupted with loss of cellular K⁺ and increase in intracellular Na⁺, Cl^- and $C{a^{{2^ + }}}$ concentrations, often depicted as “membrane failure”. Certainly these events are important for the development of cellular injury, but since they occur and are almost completed already within the first 2–4 minutes of complete ischemia, i.e. within a time period that is compatible with full neurological restitution, their exact relationship to irreversible damage is somewhat uncertain. Therefore other mechanisms operating either alone or in concert must also be considered.