Significance of acid base status, respiration, Na⁺-and K⁺-concentrations and plasma glucose for acute toxicity of TRIS (hydroxymethyl-)aminomethane in rats

Abstract

The mechanism of acute toxicity of TRIS-buffer was investigated in pentobarbital-anaesthetized Wistar-rats. An infusion of 0.5 mmol/kg · min TRIS, either pH 10.9 or pH 7.4, was tolerated for 60–70 min before death. TRIS concentration in plasma increased linearly to 53.7±9.09 mmol/l after 60 min (¯x±s_x), indicating slow uptake of the drug into tissues. Blood pressure, heart rate, ECG and Na⁺- and K⁺-concentrations in plasma and erythrocytes were not influenced by TRIS. A small rise of plasma osmolarity by 39±4.7 mosmol/l after 30 min seemed unimportant for toxicity. With alkaline TRIS a metabolic alkalosis developed and the compensatory arrest of ventilation caused a sudden drop of arterial pO₂ to 48±9 mm Hg after 50 min. A similar, though more gradual, decline of pO₂ was observed with neutralized TRIS without concomitant changes of acid-base status. Artificially ventilated rats, with constant arterial pO₂, tolerated an infusion of neutralized TRIS for at least 90 min. With TRIS of either pH plasma glucose concentration was nearly halved after 30 min. Addition of glucose (50 mg/ml) to the infusion neither prevented this effect nor increased the survival time. From these results we conclude that the main lethal action of TRIS is a depression of ventilation that, in the case of neutralized TRIS, may be related to an intracellular alkalosis.