Abstract
The purpose of our study was to characterize a novel model of FHF by experimental infection of rabbits with the rabbit hemorrhagic disease virus (RHDV). Thirty two 9-week-old rabbits were injected intramuscularly with 2x104 haemagglutination units of RHDV isolate Ast/89. About 85% of rabbits died after 36 to 54 h postinfection (pi). From 36 h pi there was a significant and marked increase in transaminases, LDH and total bilirubin. The rabbits developed hypoglycemia and coagulation abnormalities, with a significant decrease in factor V, factor VII and prothrombin levels. Plasma aromatic amino acids and taurine showed a progressive increase and the Fisher index was significantly reduced. Expression of hepatocyte growth factor messenger RNA in the liver was inhibited from 36 h pi. Liver biopsy specimens showed multiple areas of necrosis associated with haemorrhage and influx of neutrophils. Prostration and side recumbency were present at later stages and neurologic symptoms rapidly progressed to coma. Onset of brain death was found to be associated with a significant increase in intracraneal pressure and blood ammonia. In conclusion, RHDV infection reproduces a number of clinical, biochemical and histological features of the FHF syndrome and satisfies criteria for a suitable animal model of FHF.

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