Rabbit hemorrhagic viral disease Characterization of a new animal model of fulminant liver failure》.pdf

Rabbit hemorrhagic viral disease: Characterization of a new animal model of fulminant liver failure MARIA J. TUNON, SONIA SANCHEZ-CAMPOS, JAVIER GARCIA-FERRERAS, MARCELINO ALVAREZ, FRANCISCO JORQUERA, and JAVIER GONZALEZ-GALLEGO LEON, SPAIN In this study we sought to characterize a novel model of fulminant liver failure (FLF) by means of experimental infection of rabbits with the rabbit hemorrhagic disease virus (RHDV). Thirty-seven 9-week-old rabbits were injected intramuscularly with 2 4 10 hemagglutination units of an RHDV isolate. Eighty-five percent of rabbits died 36 to 54 hours after infection. From 36 hours after infection we noted marked increases in transaminases, lactate dehydrogenase, and total bilirubin. The rabbits exhibited hypoglycemia and coagulation abnormalities, with a significant decrease in factor V, factor VII, and prothrombin. Plasma aromatic amino acids and taurine showed progressive increases, and the Fischer index was significantly reduced. Expression of hepatocyte growth factor messenger RNA was inhibited from 36 hours after infection. Prostration and side recumbency were present at later stages, and neu- rologic symptoms rapidly progressed to coma. Onset of brain death was associated with a significant increase in intracranial pressure and blood ammonia. RHDV infection reproduces clinical, biochemical, and histologic features of the FLF syn- drome and satisfies criteria for a suitable ani