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

Using dose-response 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 sham-operated 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.