title: 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 (CCL4) 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 CCL4 was infused recovered spontaneously and survived; in contrast, all of five pigs that received 10 ml CCL4 died within 1.5 h after surgery. The pigs in which 7.5 ml CCL4 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 CCL4 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.
authors.affiliation: Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, Okayama, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yuasa
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Rivas-Carrillo
authors.forename: Yong
authors.initials: Y
authors.lastname: Chen
authors.forename: Nali
authors.initials: N
authors.lastname: Navarro-Alvarez
authors.forename: Alejandro
authors.initials: A
authors.lastname: Soto-Guiterrez
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Noguchi
authors.forename: Shinichi
authors.initials: S
authors.lastname: Matsumoto
authors.forename: Noriaki
authors.initials: N
authors.lastname: Tanaka
authors.forename: Naoya
authors.initials: N
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D002251:Carbon Tetrachloride / Q000633:toxicity; D004195:Disease Models, Animal; D006499:Hepatic Artery / Q000473:pathology; D022781:Hepatocytes / Q000637:transplantation; D010535:Laparoscopy; D017093:Liver Failure / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D019164:Liver, Artificial; D011169:Portal Vein / Q000473:pathology; D013552:Swine
chemical_list: D002251:Carbon Tetrachloride