PROTECTION BY TRIS(HYDROXYMETHYL)-AMINOMETHANE AGAINST BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF HYPOXIA

Pretreatment of mice with the buffer tris(hydroxymethyl)aminomethane (THAM) at alkaline but not acid pH protected against effects of anemic and histotoxic hypoxia. THAM delayed the loss of the righting reflex (from 20.3 .+-. 0.9 to 27.4 .+-. 2.0 min, P < 0.01) and death (from 24 .+-. 4 to 32 .+-. 2 min, P < 0.01) in animals with anemic hypoxia (induced with NaNO2). Alkaline THAM reduced the number of animals who lost the righting reflex after the induction of histoxic hypoxia by injection of 4 mg/kg of KCN (from 10 of 12 to 2 of 12, P < 0.01). Pretreatment with alkaline THAM also prevented the fall in acetylcholine levels and the rise in cyclic GMP induced by anemic hypoxia, and ameliorated the reduction in acetylcholine synthesis from labeled precursors in anemic (NaNO2-induced) hypoxia. Although the detailed molecular mechanisms by which THAM acts remain to be clarified, these observations may have direct clinical relevance for the care of the large number of patients in whom brain dysfunction results from conditions in which the supply of O2 to the brain is impaired but not abolished.