TY - JOUR T1 - SYNERGISM BETWEEN AMMONIA AND FATTY ACIDS IN THE PRODUCTION OF COMA: IMPLICATIONS FOR HEPATIC COMA JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 10 LP - 16 VL - 191 IS - 1 AU - Franklin J. Zieve AU - Leslie Zieve AU - William M. Doizaki AU - Robert B. Gilsdorf Y1 - 1974/10/01 UR - http://jpet.aspetjournals.org/content/191/1/10.abstract N2 - The dose-response curves for the production of coma in normal rats by single injections of ammonium salts were shifted to the left (increased responses to smaller doses) by the presence of a subcoma dose of a fatty acid, and conversely. The incidence of coma rose from 0 to 100% when the maximum subcoma doses of NH4+ and sodium octanoate were given simultaneously and the average blood NH3, increased from 1042 to 2585 µg/100 ml. A similar increase in blood NH3, was demonstrated when octanoate was replaced by hexanoate, decanoate or oleate. The blood levels of NH3, and plasma levels of free fatty acids (octanoate) at which coma occurred in normal rats were lowered substantially when both were administered simultaneously. Blood ammonias in the comatose animals varied between 50 and 2700 µg/100 ml. When the ammonium salt alone was injected, coma only occurred if the blood ammonia exceeded 2200 µg/100 ml. In 25 rats and cats in hepatic coma after acute massive liver necrosis, blood ammonias varied between 900 and 2500 µg/100 ml, and three-fourths of the animals had values below 1500 µg/100 ml. A high curvilinear correlation was observed between blood ammonia and plasma free acids in four-fifths of the animals, and with few exceptions one could predict the presence of coma from knowledge of the position of an animal about the hyperbolic line relating the two variables. The data suggest that in addition to ammonia, fatty acids probably play a significant role as a toxic factor in experimental hepatic coma. © 1974 by The Williams & Wilkins Company ER -