Rabbit hemorrhagic viral disease: characterization of a new animal model of fulminant liver failure.
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 x 10(4) 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 neurologic 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 syndrome and satisfies criteria for a suitable animal model. Rabbit hemorrhagic viral disease could provide a useful tool for the study of FLF and the evaluation of new liver-support technologies in human subjects.
Tunon
Maria J
MJ
Department of Physiology, University of León, Hospital of León, 24071 León, Spain.
Sanchez-Campos
Sonia
S
Garcia-Ferreras
Javier
J
Alvarez
Marcelino
M
Jorquera
Francisco
F
Gonzalez-Gallego
Javier
J
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001663:Bilirubin / Q000097:blood; D001774:Blood Chemical Analysis; D017250:Caliciviridae Infections / Q000097:blood / Q000473:pathology*; D004195:Disease Models, Animal; D017929:Hemorrhagic Disease Virus, Rabbit / Q000472:pathogenicity*; D017228:Hepatocyte Growth Factor / Q000235:genetics / Q000378:metabolism; D007427:Intracranial Pressure; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D017093:Liver Failure / Q000097:blood / Q000401:mortality / Q000473:pathology* / Q000821:virology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D015996:Survival Rate
D012333:RNA, Messenger; D017228:Hepatocyte Growth Factor; D007770:L-Lactate Dehydrogenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D001663:Bilirubin