Fulminant hepatic failure is a serious condition with very high mortality. Development of new
therapies designed to bridge the patient through the acute period of their disease has been hampered by the lack of a large animal model that closely reproduces the changes in humans. We have established an improved model of
fulminant hepatic failure in the pig by administration of an aminosugar d-
galactosamine hydrochloride.
Galactosamine in a dose of 1.0 g/kg was dissolved in 5%
dextrose in water (D5W) and given intravenously to seven young pigs weighing 8 to 15 kg. Seven control pigs received an equal volume of D5W alone. Two days prior to injection, a baseline ultrasound-guided liver biopsy was done in each pig under
general anesthesia using isofluorane. Clinical data were recorded and blood for laboratory determinations was drawn at 0 h (baseline), 24 h, 48 h, and 72 h after infusion of
galactosamine or D5W alone, under
general anesthesia. Neurological data were recorded at the same intervals before inducing
anesthesia.
Galactosamine-treated animals showed 100% mortality. All of them died by 86 h after injection of
galactosamine, with death resulting from
fulminant hepatic failure characterized by marked increases in total
bilirubin, liver
enzymes,
ammonia, and
lactate; associated coagulopathy;
hypoglycemia; and
coma. Liver histology showed massive hepatocellular
necrosis in all seven
galactosamine-treated animals. This large and highly reproducible animal model appears promising for future evaluation of
bioartificial liver support systems designed to treat
fulminant hepatic failure in humans.