An improved model of galactosamine-induced fulminant hepatic failure in the pig.
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.
Kalpana
K
K
Department of General Surgery, Singapore General Hospital, Singapore, 169608.
Ong
H S
HS
Soo
K C
KC
Tan
S Y
SY
Prema Raj
J
J
D000818:Animals; D001780:Blood Coagulation Tests; D001921:Brain / Q000473:pathology; D004195:Disease Models, Animal; D005688:Galactosamine; D008099:Liver / Q000473:pathology / Q000503:physiopathology; D017093:Liver Failure / Q000097:blood / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D008297:Male; D013552:Swine
D005688:Galactosamine