[Establishment of a porcine model of acute hepatic failure by intraportal injection of D-galactosamine and lipopolysaccharide].

ABSTRACT

OBJECTIVE: To develop a clinically relevant porcine model of acute hepatic failure (AHF). METHODS: Twenty-two healthy pigs were randomly divided into 5 groups group I (n = 3, intraportally administered with normal saline), group II [n = 5, intraportally administered with 1 microg/kg of lipopolysaccharide (LPS)], group III [n = 5, intraportally administered with 0.5 g/kg of D-galactosamine (D-Gal)], group IV (n = 6, intraportally administered with 0.5 g/kg of D-Gal plus 1 microg/kg LPS), and group V [n = 3, intraportally administered with 0.5 g/kg of D-Gal plus 1 microg/kg LPS and then receiving auxiliary partial orthotopic liver transplantation (APOLT)], Blood samples were collected to examine the arpartate transaminase (AST), total bilirubin, lactic acid, blood ammonia, prothrombin time (PT), blood sugar, and creatine at different time points. Autopsy was performed on the dead animals. Eight days after the APOLT laparotomy was performed again on the surviving pigs to take specimens of the original and transplanted liver to undergo pathological examination. RESULTS: All the pigs in the groups I and II survived with minimal changes in liver function tests. Two of the 5 pigs in the group III died (40%), 5 pigs in the group IV (5/6, 83%) died within 120 h, with a significant increase in aspartate transaminase 48 h after (4912 U/L +/- 759 U/L). In comparison with those of the group 1 and 2, the TBIL, blood ammonia, lactic acid, and PT 48 h after of the group 4 were all significantly higher and the blood sugar was significantly lower (all P < 0.05). Reversal of AHF in the pigs in the group V following APOLT was observed and the liver function returned near to normal level on the 7th postoperative day and regeneration of the native liver was confirmed histologically. CONCLUSION: The porcine model of AHF induced by a combination of D-gal (0.5 g/kg) and LPS (1 microg/kg) will be of much use in the development of APOLT for AHF.