Basic Research
Copyright ©2005 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 21, 2005; 11(35): 5468-5474
Published online Sep 21, 2005. doi: 10.3748/wjg.v11.i35.5468
Porcine acute liver failure model established by two-phase surgery and treated with hollow fiber bioartificial liver support system
Yi Gao, Ning Mu, Xiao-Ping Xu, Yan Wang
Yi Gao, Ning Mu, Xiao-Ping Xu, Yan Wang, Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guanzhou 510282, Guangdong Province, China
Author contributions: All authors contributed equally to the work.
Supported by the Key Technologies R and D Program of Guangdong Province during the 10th Five-Year Plan Period, No. 2002A3020206
Correspondence to: Yi Gao, Department of Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, Guangdong Province, China. mnwsq@163.com
Telephone: +86-20-85143210
Received: September 22, 2004
Revised: December 6, 2004
Accepted: December 9, 2004
Published online: September 21, 2005
Abstract

AIM: To establish a highly reproducible animal model of acute liver failure (ALF), for assessing the effect of bioartificial liver support system (BALSS).

METHODS: A two-phase complete liver devascularization procedure was performed in eight loco-hybrid pigs. Blood biochemical index and liver biopsy were studied every 2 h after surgery, and survival time was recorded. The BALSS constructed with high volume recirculating technique was a hollow fiber circulating system consisting of a hepatocyte reactor-hollow fiber module inoculated with microcarrier-adhering hepatocytes, and a double pump, heparinized, thermostabilized, micro-capsulized activated carbon-adsorbing plasmapheresis system. Twelve pigs undergoing two-phase surgery were randomized into: control group (perfused without hepatocytes, n = 6) and treatment group (perfused with hepatocytes, n = 6). Intergroup liver biochemical indexes, survival time, and liver pathological changes were analyzed at regular intervals.

RESULTS: Two-phase surgery was performed in all the experimental pigs, and there was no obvious difference between their biochemical indexes. After 3 h of phase II surgery, ammonia (Amm) increased to (269±37) μmol/L. After 5 h of the surgery, fibrinogen (Fib) decreased to (1.5±0.2) g/L. After 7 h of the surgery, ALT, AST, Tbil and PT were (7.6±1.8) nka/L, (40±5) nka/L, (55±8) μmol/L and (17.5±1.7) nka/L respectively. After 9 h of surgery, ALB and Cr were (27±4) g/L and (87±9) μmol/L. After 13 h of surgery, BUN was (3.5±0.9) μmol/L. All the above values were different from those determined before surgery. Survival time of pigs averaged 13.5±1.4 h. ALF pigs in the other group were treated with BALSS. The comparison analysis between the treated and control animals showed the changes of Tbil, PT, Alb, BUN, Cr, Fib, and Amm (P<0.01), but there was no change of ALT and AST. The survival time was statistically different (P<0.01), and there was no significant difference in histological changes.

CONCLUSION: The porcine ALF model established by two-phase devascularized surgery is valid and reproducible. The hollow fiber BALSS can meet the needs of life support and is effective in treating ALF.

Keywords: Acute liver failure; Animal model; Bioartificial liver; Micro-capsulized activated carbon adsorbing; Porcine hepatocyte