Methionine-induced hepatic coma in dogs.

Oral methionine is noncomatogenic in normal dogs, but it is consistently comatogenic in dogs with portacaval shunts in the presence of elevated ammonia levels. Such action appears to be enhanced by the ammonia itself, since relatively small doses of oral methionine can induce coma when baseline levels of ammonia are above 1,000 mug/100 ml; much higher doses are nesessary for near normal ammonemia. The methionine-induced coma closely reproduces the clinical and electroencephalographic picture of coma in other canine models. Oral methionine does not significantly increase the ammonia levels, but its action is probably mediated by the release of methanethiol (and other less active compounds) from the bowel. Methanethiol levels tend to increase in proportion to the amount of methionine administered, and its comatogenic action may be amplified, up to one hundredfold, by high ammonia levels. Methanethiol levels in comatose patients and the concept of the synergistic effect with ammonia may lead to a clearer understanding of certain enterogenous and dietetic forms of hepatic encephalopathy in cirrhotic patients. The lowering of ammonia levels by hemodialysis or methanethiol levels by activated charcoal hemoperfusion, as attempts to reverse such forms of coma, warrants further investigation.