Studies of ammonia loading: Effects of rate of delivery and enhanced removal of NH₄ on blood levels of ammonia and coma induction

Abstract

Using dose-responce curves, the dose of NH₄Ac inducing coma in one-half of the animals was increased by 60 to 80% after 1 mmol of arginine. The larger increase occurred in larger rats but was not proportional to the increase in weight. Incremental subcoma doses of NH₄ raised the amount of NH₄ required for inducing coma and the brain level of ammonia at the point of coma. After a portacaval shunt the results were similar, although lower doses of NH₄ were required from the beginning. Blood ammonias after a loading dose (1.25 mmol) of NH₄ were influenced by the duration of a preinfusion of NH₄ and by the preinjection of various amino acids involved in the disposal of NH₄ in the urea cycle. The amount of reduction in blood ammonia by ornithine and arginine compounds was less the longer the preinfusion of NH₄. Blood ammonia was not lowered by glutamate at any time but was increased with longer preinfusion periods. Hepatectomy (Hx) reduced the removal of an NH₄ load. After a modest load (0.85 mmol) of NH₄, blood ammonia increased 5-fold, over that of shamoperated rats, with 70% Hx and 15-fold with 90% Hx. Ornithine reduced these blood ammonias by about 50%. Arginine had no effect. These studies indicate ways of reducing toxicity of NH₄ and factors that predispose to or enhance toxicity.