Acetaminophen-induced acute hepatic failure in pigs: controversical results to other animal models.
To prove the function of isolated transplanted hepatocytes in acute liver failure we tried to establish a hepatic failure model in pigs which correlates to a clinical situation. In 12 pigs we administered 500-2000 mg acetaminophen/kg b.wt. after enzyme induction with pentobarbital. Seven animals receiving 500-1000 mg/kg survived the intoxication. Five animals receiving 1000-2000 mg/kg acetaminophen died within 6.5 h after intoxication because of methemoglobinemia. A close correlation between administered dosage of the drug, acetaminophen blood levels, and methemoglobinemia was found. Histology of surviving animals showed a dosage-dependent cell necrosis. A standardized hepatic failure model could not be established in pigs by acetaminophen intoxication because dosages of less than 1000 mg/kg were survived. In dosages higher than 1000 mg/kg a side-effect of the acetaminophen intoxication, i.e., methemoglobinemia, limited the life of the animals. Therefore, acetaminophen cannot be used to induce acute hepatic failure in pigs.
Henne-Bruns
D
D
Dept. of Surgery, University of Hamburg, Federal Republic of Germany.
Artwohl
J
J
Broelsch
C
C
Kremer
B
B
D000082:Acetaminophen / Q000008:administration & dosage / Q000633:toxicity*; D000208:Acute Disease; D000758:Anesthesia; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000473:pathology; D008297:Male; D008706:Methemoglobin / Q000032:analysis; D013552:Swine / Q000502:physiology*
D000082:Acetaminophen; D008706:Methemoglobin