Encephalopathy from acute liver failure and from acute hyperammonemia in the rabbit. A clinical and biochemical study.
To study the molecular basis of ammonia toxicity, highly reproducible models of acute liver failure and acute hyperammonemia in the rabbit were developed. Acute liver failure was induced by two-stage liver devascularization, and acute hyperammonemia by prolonged ammonia infusion such that the plasma ammonia pattern found in acute liver failure was simulated. Clinical symptoms, spectral analysis of the EEG, biochemistry (blood gases, renal function, electrolytes and markers of hepatic injury) and the presence of cerebral edema were studied. During acute liver failure severe encephalopathy developed after 10.2 +/- 1.9 h (n = 6, mean +/- SEM). Other liver-failure-associated abnormalities were cerebral edema, lactic acidosis, renal dysfunction, hypothermia and septicemia. During acute hyperammonemia, severe encephalopathy developed after 18.2 +/- 0.4 h (n = 6, mean +/- SEM). Other abnormalities found were cerebral edema and lactic acidosis. In both animal models comparable EEG changes were observed (a decrease in mean dominant frequency and theta-activity, and an increase in delta activity). However, these changes were not statistically significant, and non-specific as they also occurred in control rabbits despite their clinical wellbeing. This study demonstrates in the rabbit the similarity between encephalopathy due to acute ischemic liver failure and that due to hyperammonemia. An observed difference in hyperammonemia-induced encephalopathy was pronounced ataxia, which did not occur during acute liver failure, whereas hypothermia, sepsis and renal failure occurred exclusively in acute liver failure. Our models appear satisfactory for the study of hepatic encephalopathy and ammonia toxicity.
de Knegt
R J
RJ
Department of Internal Medicine II, Erasmus University Rotterdam, The Netherlands.
Groeneweg
M
M
Schalm
S W
SW
Hekking-Weijma
I
I
D000641:Ammonia / Q000009:adverse effects / Q000097:blood*; D000818:Animals; D001929:Brain Edema / Q000209:etiology* / Q000378:metabolism; D004195:Disease Models, Animal; D004569:Electroencephalography; D006501:Hepatic Encephalopathy / Q000209:etiology* / Q000378:metabolism; D017114:Liver Failure, Acute / Q000209:etiology; D011817:Rabbits
D000641:Ammonia