Laparoscopy-assisted creation of a liver failure model in pigs

Takeshi Yuasa, Tsuyoshi Yamamoto, Jorge D. Rivas-Carrillo, Yong Chen, Nalú Navarro-Alvarez, Alejandro Soto-Guiterrez, Hirofumi Noguchi, Shinichi Matsumoto, Noriaki Tanaka, Naoya Kobayashi

Research output: Contribution to journalArticle

8 Scopus citations

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 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.

Original languageEnglish (US)
Pages (from-to)187-193
Number of pages7
JournalCell Transplantation
Volume17
Issue number1-2
DOIs
StatePublished - Jan 1 2008

Keywords

  • Carbon tetrachloride
  • Hepatic failure
  • Laparoscopy
  • Pigs

ASJC Scopus subject areas

  • Biomedical Engineering
  • Cell Biology
  • Transplantation

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    Yuasa, T., Yamamoto, T., Rivas-Carrillo, J. D., Chen, Y., Navarro-Alvarez, N., Soto-Guiterrez, A., Noguchi, H., Matsumoto, S., Tanaka, N., & Kobayashi, N. (2008). Laparoscopy-assisted creation of a liver failure model in pigs. Cell Transplantation, 17(1-2), 187-193. https://doi.org/10.3727/000000008783906973