title: Splenic transposition is superior to caudal shunt as a model of murine total hepatic ischemia.
abstract: Murine total hepatic ischemia (THI) followed by reperfusion without shunting of the portal vein induces significant lethality in rodents due to intestinal congestion. Two methods have been promulgated to study THI and reperfusion in mice without intestinal congestion: subcutaneous splenic transposition which creates a portosystemic shunt via epigastric vessels, and a caudal shunt with 30% hepatectomy, which creates a portosystemic shunt via the small remnant of remaining caudal lobe. We compared outcome, inflammatory response and hepatic injury due to THI and reperfusion in these two models. Female C57BL/6 mice underwent ST, caudal shunt or no surgery prior to having 30 min of total hepatic ischemia followed by 60 min of reperfusion. Survival, surgical complications, serum AST/ALT and IL-6 were determined. Apoptotic and necrotic hepatocytes were identified by morphological criteria. Complication rates for the ST and caudal shunt procedures were 6.7 and 20%, respectively. Subsequent mortality rates following THI and 60 min reperfusion were 5.9 and 50% in mice with ST and caudal shunt, respectively. Both groups had elevated serum AST/ALT concentrations. However, in mice undergoing caudal shunt, AST/ALT levels were also significantly increased even without THI. The number of apoptotic hepatocytes after THI and reperfusion in mice following caudal shunt was significantly higher compared with those of ST (P<0.001). Both ST and caudal shunt can be used in models of THI and reperfusion to prevent significant lethality due to intestinal congestion. However, ST is a simple, safe and suitable model, whereas caudal shunt requires manipulation of the liver, and is associated with significant hepatic injury and morbidity.
authors.affiliation: Department of Surgery, University of Florida College of Medicine, Gainesville, FL 32610-0286, USA.
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Philip A
authors.initials: PA
authors.lastname: Efron
authors.forename: Hironori
authors.initials: H
authors.lastname: Tsujimoto
authors.forename: Sven K
authors.initials: SK
authors.lastname: Tschoeke
authors.forename: Ricardo
authors.initials: R
authors.lastname: Ungaro
authors.forename: Shiro
authors.initials: S
authors.lastname: Fujita
authors.forename: David P
authors.initials: DP
authors.lastname: Foley
authors.forename: Alan
authors.initials: A
authors.lastname: Hemming
authors.forename: Lyle L
authors.initials: LL
authors.lastname: Moldawer
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D006498:Hepatectomy; D007422:Intestines / Q000098:blood supply / Q000473:pathology; D008107:Liver Diseases / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D051379:Mice; D008810:Mice, Inbred C57BL; D011170:Portasystemic Shunt, Surgical; D015427:Reperfusion Injury / Q000401:mortality / Q000503:physiopathology / Q000601:surgery*; D013154:Spleen / Q000503:physiopathology / Q000637:transplantation*; D015996:Survival Rate; D013997:Time Factors