J Korean Med Sci.  2005 Jun;20(3):427-432. 10.3346/jkms.2005.20.3.427.

An Experimental Animal Model of Fulminant Hepatic Failure in Pigs

• Lee KU
• Zheng LX
• Cho YB
• Kim KH
• Ha J
• Suh KS
• Jung SE

• KMID: 1778501
• DOI: http://doi.org/10.3346/jkms.2005.20.3.427

Abstract

The objective of this study was to develop an experimental animal model of fulminant hepatic failure to test the efficacy of the bioartificial liver system. The portal vein and the hepatic artery were clamped intermittently and then the hepatic artery was ligated (ligation group, n=5). Pigs whose hepatic arteries were not ligated after clamping were assigned to the non-ligation group (n=5). The biochemical changes in blood, histologic alterations of the liver and neurologic examination for pigs were checked up. All animals died within 17 hr in the ligation group. On the other hand, all animals survived more than 7 days in the non-ligation group. In the ligation group, the levels of ammonia, lactic acid and creatinine showed a progressively increasing pattern. Prothrombin time was also prolonged gradually. Cytoplasmic condensation and nuclear pyknosis of hepatocytes were detected histologically at autopsy. Neurologic findings such as decreased pain sensation, tachypnea and no light reflex of pupils were observed. The findings shown in the ligation group are similar to the clinical features of fulminant hepatic failure in human and this animal model is reproducible. Therefore, this can be a suitable animal model to evaluate the efficacy of the bioartificial liver system for treating fulminant hepatic failure.

Keyword

Models, Animal; Liver Failure, Acute; Hepatic Artery; Hepatic Encephalopathy

MeSH Terms

Acidosis/etiology/prevention & control
Ammonia/blood
Animals
Aspartate Aminotransferases/blood
Bilirubin/blood
Blood Glucose/metabolism
Blood Urea Nitrogen
Comparative Study
Creatinine/blood
*Disease Models, Animal
Female
Hepatic Artery/surgery
Lactic Acid/blood
Ligation/adverse effects
Liver Failure, Acute/blood/*pathology
Portal Vein/surgery
Potassium/blood
Prothrombin Time
Research Support, Non-U.S. Gov't
Sodium Bicarbonate/pharmacology
Swine

Figure

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  Fig. 1 Evolution of ammonia and lactic acid (mean±SD) before clamping, after 4 hr and 7 hr since the first clamping, and before death (in non-ligation group, 20 hr after clamping).

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  Fig. 2 Evolution of total bilirubin, AST, and ALT (mean±SD) before clamping, after 4 hr and 7 hr since the first clamping, and before death (in non-ligation group, 20 hr after clamping).

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  Fig. 3 Evolution of BUN, creatinine, and potassium (mean±SD) before clamping, after 4 hr and 7 hr since the first clamping, and before death (in non-ligation group, 20 hr after clamping).

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  Fig. 4 Evolution of glucose and PT (mean±SD) before clamping, after 4 hr and 7 hr since the first clamping, and before death (in non-ligation group, 20 hr after clamping). The PT was not checked in the third measure after the clamping, that is, in the time when it has passed 7 hr since the first clamping.

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  Fig. 5 (A) Hematoxylin-eosin-stained specimen before clamping the portal triad in pigs (×100). Image shows normal portal tract in the pig liver. (B) Specimen after 4 hr since the first clamping in the non-ligation group (×100). Widened portal spaces with infiltration of a few inflammatory cells and ischemic changes of hepatocytes in porto-to portal space are shown but there are no necrotic hepatocytes. The sinusoidal spaces are dilated. (C) Specimen after 20 hr since the first clamping in the non-ligation group (×100). There are no histologic differences from those of (B).

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  Fig. 6 Hematoxylin-eosin-stained specimen after 4 hr since ligating the hepatic artery in pigs (×100). The findings are similar to those of the non-ligation group but, cytoplasmic condensation and unclear pyknosis in focal areas are found.

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  Fig. 7 Hematoxylin-eosin-stained specimens at autopsy in the ligation group (×400). The histologic features mentioned at Fig. 5B and Fig. 6 are also shown. In addition parenchymal hemorrhage, necrosis, nuclear pyknosis and cytoplasmic condensation in multifocal areas are shown.

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