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 (Po0.001). 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. Keywords: intestinal congestion; mouse; portal hypertension; splenic transposition; total hepatic ischemia and reperfusion Total hepatic ischemia (THI) and reperfusion injury are inevitable consequences of various surgical maneuvers that occur during hepatobiliary surgery, liver transplantation and hepatic trauma surgery. 1 Models of hepatic warm ischemia in rodents have been instrumental in elucidating mechanisms of injury during liver transplantation and hepatic ischemic/reperfusion injury.In humans and primates, occlusion of the hepatoduodenal ligament (containing the portal vein, hepatic artery and the common bile duct) is well tolerated because of a more efficient portosystemic collateral network through which splanchnic blood can return to the heart (Pringle maneuver 2 ). Interruption of blood flow to the normothermic liver is safe for at least 60 min even without a venous bypass to decompress the vasculature proximal to the occlusion. 3 In contrast, THI in rodents has been shown to produce several pathologic events, including splanchnic congestion, severe intestinal ischemia, mesenteric congestion and systemic shock. 4 Consequently, these animals poorly tolerate even short periods of total hepatic ischemia. For example, 30 min of ischemia induces an immediate and delayed intestinal barrier failure, w...

Development of a Porcine Model of Post-Hepatectomy Liver Failure

“…A vasoconstrictive response of the liver remnant due to ischemia/reperfusion injury may have also been a factor in the development of portal hypertension [31,40]. In our experiments, the pathology findings of portal space and sinusoidal congestion, as well as hepatocyte swelling are also consistent with portal hypertension.…”

“…It is well known that the human liver can safely withstand warm ischemia for 45-60 min without portosystemic shunt [24][25][26][27]. .In contrast, rodents and pigs can poorly tolerate even short periods of total hepatic ischemia [28][29][30][31][32][33][34]. It has been shown that 50% of rats with 45-min warm ischemia of the liver died within 7 d and no rat survived after completely blocking the hepatic artery and portal vein for 60 min [24].…”

Liver epithelial cells proliferate under hypoxia and protect the liver from ischemic injury via expression of HIF-1 alpha target genes

“…The spleen was pulled out and buried in subcutaneous pouch. 12 This surgical procedure prevents portal congestion caused by PTO and enabled animals to survive. Three weeks after SST, portal trunk was ligated with 5-0 nylon sutures.…”

Efficient nonarterialized mouse liver transplantation using 3‐dimensional–printed instruments

“…The portal clamping time in the recipient was defined as the period from the positioning of the portal clamp before removing the recipient's liver, to its removal after the completion of the suprahepatic and portal anastomoses. It is linked to animal survival because rodents are particularly sensitive to the metabolic effects caused by splanchnic congestion . The portal clamping time was constantly within 15 minutes, with a median at 12.5 ± 2.0 minutes (mean, 12.2 minutes).…”