Blood ammonia elevation and toxicity from intravenous L-amino acid administration to dogs: the protective role of L-arginine.

Abstract

A nontoxic intravenous l-amino acid mixture became markedly toxic when l-arginine and l-histidine were deleted from the mixture and was capable of producing convulsions and death in dogs. Associated with these infusions was a marked increase in blood ammonia levels that coincided with the signs of toxicity. Similar toxicity was produced by infusion of ammonium salts. Administration of l-arginine·HCl prior to or with the infused amino acid mixture prevented the toxicity and the blood ammonia rise. Subsequent injection of l-arginine·HCl produced a prompt fall in blood ammonia to normal levels. l-Ornithine·HCl or l-citrulline·HCl were similarly effective. d-Arginine·HCl and l-histidine·HCl were ineffectual. Urea production was more rapid when l-arginine was added to the infused amino acid mixture. The results suggest that the Krebs-Henseleit cycle is a functioning metabolic pathway that normally is a major deterrent to the accumulation of excessive blood ammonia when large amounts of amino acids are infused.