Laparoscopy-Assisted Creation of a Liver Failure Model in Pigs

Abstract

We created a hepatic failure pig model that was suitable for the assessment of cell therapies, such as hepatocyte transplantation and bioartificial livers, using a laparoscopic surgical technique. In our model, all of three hepatic arteries were resected, 5, 7.5, or 10 ml of carbon tetrachloride (CCL 4 ) was injected into the liver through the portal vein, and subsequently the portal vein was mechanically occluded for 30 min. After the portal occlusion was released, a liver biopsy was performed, and then the surgery was completed. Blood samples were regularly taken during the surgery in order to perform biochemical examinations. All of five pigs in which 5 ml of CCL 4 was infused recovered spontaneously and survived; in contrast, all of five pigs that received 10 ml CCL 4 died within 1.5 h after surgery. The pigs in which 7.5 ml CCL 4 was administered developed liver failure and survived for 6.4 h on average (±1.4 SD). Induction of liver failure with the use of 7.5 ml CCL 4 and 30-min hepatic ischemia fulfilled five of the six criteria that were proposed by Terblanche and Hickman: reversibility, reproducibility, death from liver failure, a therapeutic window, and a large-animal model. We believe that our model is the first report on creation of a reliable model for liver failure in pigs to assess the efficacy of liver-targeted cell therapies.