TY - JOUR
T1 - Laparoscopy-assisted creation of a liver failure model in pigs
AU - Yuasa, Takeshi
AU - Yamamoto, Tsuyoshi
AU - Rivas-Carrillo, Jorge D.
AU - Chen, Yong
AU - Navarro-Alvarez, Nalú
AU - Soto-Guiterrez, Alejandro
AU - Noguchi, Hirofumi
AU - Matsumoto, Shinichi
AU - Tanaka, Noriaki
AU - Kobayashi, Naoya
PY - 2008
Y1 - 2008
N2 - 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.
AB - 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.
KW - Carbon tetrachloride
KW - Hepatic failure
KW - Laparoscopy
KW - Pigs
UR - http://www.scopus.com/inward/record.url?scp=42249110527&partnerID=8YFLogxK
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U2 - 10.3727/000000008783906973
DO - 10.3727/000000008783906973
M3 - Article
C2 - 18468249
AN - SCOPUS:42249110527
SN - 0963-6897
VL - 17
SP - 187
EP - 193
JO - Cell Transplantation
JF - Cell Transplantation
IS - 1-2
ER -