Hypoxia and ammonia toxicity

¹ Laboratory of Parasitic Diseases and Laboratory of Clinical Investigation National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland

Ammonia toxicity was strikingly potentiated by short periods of hypoxia. The toxicity (ld₅₀) of ammonium chloride administered intravenously to mice after 2 minutes in 15% oxygen was the same as that in 21% oxygen. However, its toxicity began to increase when they were exposed to 13% oxygen, and was markedly enhanced by each 2% decrement in oxygen concentration. The effect of a maximal lethal dose in 7% oxygen could be completely reversed in a matter of seconds by transferring the mice to 21% oxygen. Ninety-nine per cent oxygen did not alter the ld₅₀, but significantly prolonged life. Hypoxia had a relatively slight effect on Metrazol toxicity. Blood pH was unchanged by the short periods of hypoxia prior to ammonia injection. Furthermore, measurements of brain ammonia concentrations following a standard dose of ammonium chloride at 21, 11 and 7% oxygen revealed that hypoxia had no effect on ammonia uptake or detoxication by the brain. It appeared therefore, that hypoxia directly potentiated the toxic effect of ammonia on the brain.

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