Hypoxia and ammonia toxicity

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Abstract
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.