Liver regeneration and hemodynamics in pigs with mesocaval shunt.

BACKGROUND: A surgical technique using a mesocaval shunt and downstream ligation of the superior mesenteric vein has been recently proposed to overcome the size limitations that restrict the use of partial liver grafts. We designed an experimental study in pigs to evaluate the capacities of liver regeneration and hemodynamic changes after completion of this procedure. MATERIAL AND METHODS: Liver regeneration after left hepatectomy was compared between two groups of five pigs, with or without mesocaval shunt, sacrificed 11 to 14 days after surgery. A third group of five animals was used for hemodynamic studies. RESULTS: Liver regeneration in study animals was 45.3% of controls. This was obtained despite a reduction of the venous inflow to 15.6% of the control, resulting in a net decrease of the total blood inflow to 56% of the control, despite a compensatory increase in the arterial inflow. There was no significant difference in mitotic index, hepatocellular size, and glycogen content between study and control animals. CONCLUSION: Our experimental study confirms that the regenerative capacities of the pig liver are largely preserved despite the dramatic reduction of the venous blood inflow, reduced to its gastroduodenosplenopancreatic component. This lends further support to the hypothesis that the gastroduodenosplenopancreatic blood is enriched in hepatotrophic factors, likely to originate from the pancreas and duodenum.

Uncoupling the systemic circulation and the Ex Vivo circuit during experimental isolated liver perfusion.

Performing an ex vivo liver perfusion as a transient liver support requires perfusing the liver with a flow of 1 ml/min per kg of liver, which could reach 25% of the cardiac output when a human liver is used. This high flow could be detrimental in patients with acute liver failure. Therefore, in an ischemic-induced liver failure pig model, we developed a circuit allowing low flows going out of and into the systemic circulation, whereas the flow going through the ex vivo liver is maintained at a high value. This was obtained by uncoupling the ex vivo circuit from the systemic circulation. Ex vivo liver perfusion was performed in a closed circuit with a flow averaging 1 ml/min per kg of ex vivo liver (700 to 800 ml/min, according to the weight of the livers we used). It was linked to the systemic circulation with input and output flows equal to that used during hemodialysis (200 ml/min). Compared with previously reported direct circuits, this perfusion system was well tolerated from a circulatory point of view. After the induction of ischemic liver failure, the ex vivo liver perfusion led to an increase in urea, branched amino acids to aromatic amino acid ratio, and fractional clearance of indocyanine green and galactose and to a decrease in ammonia and lactic acid. This system allowed the ex vivo liver to keep its clearing properties despite a low extracorporeal flow. It represents an extracorporeal circuit that could be used in place of the direct extracorporeal high-flow liver perfusion.

The outcome of 400 consecutive liver grafts using the aortic perfusion-only technique.

The goal of this study is to establish the effect of cadaveric liver retrieval, using the technique of aortic perfusion only, on liver graft function, and to identify associated potential risk factors for graft dysfunction. The authors reviewed the outcome of 400 consecutive, orthotopic, cadaveric liver transplantation retrieved by the technique of aortic perfusion only. Relevant parameters pertaining to the donor, recipient, procurement, graft and peri-operative variables are analyzed to assess their influence on graft function. The univariant analysis revealed that donor age, body mass index, blood pressure, and vasopressor dependence influence graft function. Furthermore, predictors of dysfunction included prolonged anhepatic phase, transplantation duration and partial grafts. In addition, multivariant analysis revealed significant association between obesity of donors, partial graft, and dysfunction. The technique of aortic perfusion only, is a simple and reproducible procedure. The post-transplantation outcomes appear to be similar to those reported for the traditional liver procurement technique.

Liver function during extracorporeal whole liver perfusion in a pig model of acute ischemic liver failure.

The shortage of livers for transplant has renewed interest in the potential of temporary liver support such as extra corporeal whole liver perfusion. In an ischemic induced liver failure model we perfused an extra corporeal liver through only a portal vein and assessed the function of this ex vivo liver by using hepatic tests to estimate elimination as well as synthesis capacities. Acute liver failure was performed in five control pigs by a hepatic devascularization associated to an end to side portocaval shunt. In a treated group, 5 to 6 h after this hepatic devascularization, animals were connected to an extra corporeal liver perfused via the portal vein with blood withdrawn from the ischemic liver animal from its portal vein. Devascularization of the liver induced an increase in liver enzymes and ammonia, a drop in the ratio of branched chain amino acids to aromatic amino acids, and a decrease in blood urea and indocyanine green and galactose clearances. In treated animals, urea, amino acid ratio, and clearances increased after the ex vivo liver perfusion. In this group, mean bile production and mean liver oxygen consumption were 13.7 +/- 3.6 ml/h and 16.1 +/- 7.7 ml/min, respectively. In an acute ischemic liver failure pig model, an extra corporeal whole liver perfusion demonstrated detoxification properties as well as synthesis capacities.

Portomesenteric disconnection for small-for-size grafts in liver transplantation: Preclinical studies in pigs.

This study reviews the evaluation and results of a new liver transplantation technique for small-for-size grafts with portomesenteric disconnection. Twenty Large-White pigs underwent heterotopic liver transplantation after a mesocaval shunt, ligation of the superior mesenteric vein downstream from the shunt, and ligation of the recipient portal vein near the native liver. The donor-to-recipient weight ratio was 24%, and the graft-to-recipient weight ratio was 0.6%. In five control pigs, no mesocaval shunt was performed. The mesocaval shunt provided diversion of 60% of the splanchnic blood flow. The median survival of study pigs was 39 days (range, 8 to 98). Median serum bilirubin levels at 1 week were 12 micromol/L (range, 4 to 59). At autopsy, graft weight was increased to 2.7 times the initial weight and histologic findings were normal. In the control group, all pigs died quickly of acute splanchnic congestion. Portomesenteric disconnection was effective to achieve survival of small-for-size grafts in pig liver transplantation.

Small-for-size partial liver graft in an adult recipient; a new transplant technique.

We report a new technique of adult liver transplantation using a small-for-size graft. In order to avoid graft congestion and failure by overperfusion, we completely diverted the superior mesenteric venous flow by a mesocaval shunt with downstream ligation of the superior mesenteric vein. The recipient recovered well, and the graft had normal histology and function at 5 months follow-up. Given the current scarcity of cadaveric donors, this technique may increase the numbers of adult recipients by using left lobes from cadaveric split liver grafts.