A New Liver Autotransplantation Technique Using Subnormothermic Machine Perfusion for Organ Preservation in a Porcine Model
Department of Surgical and Gastroenterological Sciences, Hepatobiliary and Liver Transplant Unit, University of Padova, Italy. Transplantation Proceedings
(Impact Factor: 0.98).
05/2011; 43(4):997-1000. DOI: 10.1016/j.transproceed.2011.01.139
Hepatic resection is the gold standard of therapy for primary and secondary liver tumors, but few patients are eligible for this procedure because of the extent of their neoplasms. Improvements in surgical experience of liver transplantation (OLT), hepatic resection and preservation with sub-normothermic machine perfusion (MP) have prompted the development of a new model of large animal autotransplantation.
Landrace pigs were used in this experiment. After intubation, hepatectomy was performed according to the classic technique. The intrahepatic caval vein was replaced with a homologous tract of porcine thoracic aorta. The liver was perfused with hypothermic Celsior solution followed by MP at 20 °C with oxygenated Krebs solution. An hepatectomy was performed during the period of preservation, which lasted 120 minutes, then the liver was reimplanted into the same animal in a 90° counterclockwise rotated position. The anastomoses were performed in the classic sequence. Samples of intravascular fluid, blood and liver biopsies were obtained at the end of the period of preservation in MP and again at 1 and 3 hours after liver reperfusion to evaluate graft function and microscopic damage.
All animals survived the procedure. The peak of aspartate aminotransferase was recorded 60 minutes after reperfusion and the peak of alanine aminotransferase and lactate dehydrogenase after 180 minutes. Histopathologic examination under the light microscope identified no necrosis or congestion. Intraoperative echo-color Doppler documented good patency of the anastomosis and normal venous drainage.
This system made it possible to perform hepatic resections and vascular reconstructions ex situ while preserving the organ with mechanical perfusion (ex vivo, ex situ surgery). Improving surgical techniques regarding autotransplantation and our understanding of ischemia-reperfusion damage may enable the development of interesting scenarios for aggressive surgical treatment or radiochemotherapy options to treat primary and secondary liver tumors unsuitable for conventional in situ surgery.
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- "Surprisingly, an oxygen carrier is not always used; SMP has been performed both with and without red blood cells or an artificial oxygen carrier.    The question whether the of an oxygen carrier at subnormothermic temperatures is essential, therefore, remains a matter of debate and this issue requires further research. "
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ABSTRACT: The high incidence of non-anastomotic biliary strictures (NAS) after transplantation of livers from extended criteria donors is currently a major barrier to widespread use of these organs. This review provides an update on the most recent advances in the understanding of the etiology of NAS. These new insights give reason to believe that machine perfusion can reduce the incidence of NAS after transplantation by providing more protective effects on the biliary tree during preservation of the donor liver. An overview is presented regarding the different endpoints that have been used for assessment of biliary injury and function before and after transplantation, emphasizing on methods used during machine perfusion. The wide spectrum of different approaches to machine perfusion is discussed, including the many different combinations of techniques, temperatures and perfusates at varying time points. In addition, the current understanding of the effect of machine perfusion in relation to biliary injury is reviewed. Finally, we explore directions for future research such as the application of (pharmacological) strategies during machine perfusion to further improve preservation. We stress the great potential of machine perfusion to possibly expand the donor pool by reducing the incidence of NAS in extended criteria organs.
Copyright © 2015. Published by Elsevier B.V.
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- "Although erythrocytes or artificial oxygen carriers added to the perfusate are effective in delivering oxygen to the liver [11,18,27,28], Vairetti et al. successfully used oxygenated SNMP without an oxygen carrier to investigate the temperature-dependence and functional integrity of the graft postperfusion [29,30]. Recently, Gringeri et al. applied SNMP without an oxygen carrier to liver grafts for 120 minutes in a porcine model of autotransplantation . Moreover, Tolboom et al. calculated the oxygen use of livers during machine perfusion at 20°C and 30°C with an oxygen carrier and concluded that though livers consume more oxygen at 37°C, the addition of the oxygen carrier was not required for adequate liver metabolism at room temperature . "
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Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. Herein we present a simplified machine perfusion system without the need for oxygen carriers or temperature control, which we validated in a model of orthotopic liver transplantation.
Rat livers were procured and subnormothermically perfused with supplemented Williams E medium for 3 hours, then transplanted into healthy recipients (Fresh-SNMP group). Outcome was compared with static cold stored organs (UW-Control group). In addition, a rat liver model of donation after cardiac death was adapted using a 60-minute warm ischemic period, after which the grafts were either transplanted directly (WI group) or subnormothermically perfused and transplanted (WI-SNMP group).
One-month survival was 100% in the Fresh-SNMP and UW-Control groups, 83.3% in the WI-SNMP group and 0% in the WI group. Clinical parameters, postoperative blood work and histology did not differ significantly between survivors.
This work demonstrates for the first time in an orthotopic transplantation model that ischemically damaged livers can be regenerated effectively using practical subnormothermic machine perfusion without oxygen carriers.
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ABSTRACT: Experimental animal research has been pivotal in the development of clinical liver transplantation (LTx). Results obtained in these experiments have been applied in clinic and clinical challenges have been scrutinized in animal laboratories. Porcine model is an optimal model in the field of experimental LTx research. Here, we present the various techniques of experimental LTx in the porcine model in detail. Different methods and modifications have been described. The following major steps have been discussed in detail: donor liver preparation, recipient operation including recipient hepatectomy, and reconstruction phase, including the reconstruction of suprahepatic inferior vena cava (SHIVC), portal vein (PV), infrahepatic inferior vena cava (IHIVC), hepatic artery (HA) and bile duct (BD). IHIVC and SHIVC are anastomosed end to end directly or with the use of prosthesis anastomosed side to side. The PV anastomosis is performed end to end between donor and recipient PV, Cuff method or Stump method. Arterialization has been accomplished via carrel patch or donor HA end to end with recipient HA. There are three major methods for reconstruction of BD: end to end or end to side choledochocholedochostomy or choledojejunostomy with Roux-en-Y jejunal loop. Each method has advantages and disadvantages regarding the objectives of the study; the most physiological techniques may be preferred for long-term survival studies, while the faster techniques may be selected for experimentations aiming the direct postoperative phase.
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