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 acu te 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 o f 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 eq ual volume of D5W alone. Two days prior to injection, a baseline ultrasound -guided liver biopsy was done in each pig under general anesthesia using is ofluorane. Clinical data were recorded and blood for laboratory determinati ons was drawn at 0 h (baseline), 24 h, 48 h, and 72 h after infusion of gal actosamine or D5W alone, under general anesthesia. Neurological data were r ecorded at the same intervals before inducing anesthesia. Galactosamine-tre ated animals showed 100% mortality. All of them died by 86 h after injectio n of galactosamine, with death resulting from fulminant hepatic failure cha racterized by marked increases in total bilirubin, liver enzymes, ammonia, and lactate; associated coagulopathy; hypoglycemia; and coma. Liver histolo gy showed massive hepatocellular necrosis in all seven galactosamine-treate d animals. This large and highly reproducible animal model appears promisin g for future evaluation of bioartificial liver support systems designed to treat fulminant hepatic failure in humans. (C) 1999 Academic Press.