A reproducible large animal model of fulminant hepatic failure was developed in the anesthetized dog by the administration of the amino sugar D-galactosamine. Galactosamine in 5% dextrose in water (D5W), was given as an intravenous bolus to 10 young male dogs weighing 27 to 30 kg. Three dogs that received an equal volume of D5W alone served as controls. Galactosamine at 0.5 g/ kg (n = 5) produced significant biochemical evidence of liver injury with 100% survival at 48 hours. Galactosamine 1.0 g/kg (n = 5) yielded in 100% 48-hour mortality resulting from fulminant liver failure characterized by a progressive increase in liver enzymes, total bilirubin, ammonia, and lactate and associated coagulopathy, hypoglycemia, coma, and increased intracranial pressure. Necropsy showed liver pallor, ascites, and brain swelling. Liver histology showed significant hepatocellular necrosis. This clinically relevant large animal model will enable the quantitative evaluation of new technologies, such as the bioartificial liver, for the support of hepatic failure in humans.
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Abbreviations: FHF, fulminant hepatic failure; IV, intravenous. From the Departments of 1Surgery, 2Medicine, and 4Chemical Engineering and Materials Sciences, University of Minnesota, Minneapolis; and 3Cellex Biosciences, Coon Rapids, MN. Received January 10, 1994; accepted October 4, 1994. Supported by a grant from Cellex Biosciences, Coon Rapids, MN. Address reprint requests to: Frank B. Cerra, MD, Professor of Surgery, Department of Surgery, University of Minnesota Hospitals and Clinic, Box 42, Minneapolis, MN 55455. Copyright © 1995 by the American Association for the Study of Liver Diseases. 0270-9139/95/2103-002853.00/0