Protective role of normothermic machine perfusion during reduced‐size liver transplantation in pigs

Abstract

The purpose of this study is to explore whether normothermic machine perfusion (NMP) preservation is superior to cold preservation during reduced-size liver transplantation (RSLT) in pigs. Twenty-four healthy Ba-Ma mini pigs were used (aged >13 months; weight 25-35 kg; regardless of sex). The animals were randomized into 2 groups. In group A (NMP), donor livers were harvested without warm ischemia time and heartbeats and then were connected to the NMP system to reduce the livers' size under the normothermic condition. In group B (University of Wisconsin [UW] solution), donor livers were harvested without warm ischemia time and heartbeats after being perfused by UW solution and were then preserved in 08C-48C UW solution to reduce the livers' size under cold conditions. After that, liver transplantation without venovenous bypass was performed. General RSLT information of the pigs from the 2 groups was recorded; the serological indices were measured; and routine pathological examination of liver tissue was observed. A significant difference was observed in the intraoperative bleeding between the 2 groups (P < 0.05), whereas no significant difference was found in the other indices (all P > 0.05). Significant differences of alanine aminotransferase levels, aspartate aminotransferase levels, and lactate dehydrogenase levels between the 2 groups were observed between postoperative days 3 and 5 (P < 0.05). Significant differences of lactic acid levels between the 2 groups were observed between postoperative days 2 and 5 (P < 0.05). Compared with the cold preservation group, the liver tissues of the NMP preservation group only rarely experienced liver cell necrosis and maintained integrities in the hepatic sinusoid spaces and endothelial cells. In conclusion, NMP preservation is superior to cold preservation during RSLT in pigs.Liver Transplantation 22 968-978 2016 AASLD. Liver transplantation is an effective therapeutic approach for end-stage liver disease. However, although this technique is mature and well recognized, an increasing number of patients requiring liver transplantation die on the waiting list. It is estimated that the overall fatality rate of patients on the waiting list is over 10%, and of this rate, more than 20% are children recipients. (1,2) The main reason is that there would never be enough pediatric donors to meet the needs of children in whom biliary atresia was the main indication for liver transplantation, (3) and a discrepancy in size between a small recipient and a large liver graft sometimes makes a reduction of the graft necessary to avoid difficulty in abdominal closure and respiratory impairment. (4) To solve this problem, in 1969, Gans (5) performed heterotopic partial liver transplants, which was reported by Fortner et al. (6) in 1979. Bismuth and Houssin (7) are credited with the first orthotopic partial liver transplant in 1984, when they transplanted the left hemiliver with the inferior vena cava in the standard manner, from a 75-kg adult to a 10-year-old 26-kg recipient. This method...

Translational Advances of Hydrofection by Hydrodynamic Injection

“…An isolated organ model with vascular perfusion and the possibility of keeping an entire human liver viable for a few days should allow us to evaluate the entire decoding process after hydrofection, from delivery to protein translation and export into the circulating medium. At present, different devices for maintaining liver circulation ex vivo are being used in the field of liver transplantation, such as Organox ® and other experimental systems have been proposed [ 159 ]. Our group has already designed and constructed a preliminary system offering the possibility of liver maintenance for up to two days for preclinical studies.…”

Preventing Tumour Recurrence after Liver Transplantation: The Role of Machine Perfusion

“…An induction of inflammatory pathways was shown in different organs. Zhang et al compared NMP with SCS in a reduced-size LT pig model and confirmed the presence of serum markers of oxidative tissue damage (malondialdehyde) and inflammatory cytokines (TNF-α, IL-1, IL-6) postoperatively [113]. In order to provide the complete picture, it would be of interest not only to measure the plasma levels of inflammatory markers, which were significantly lower in the NMP group, but also to quantify the same markers in the perfusates obtained from the device [113].…”

“…Zhang et al compared NMP with SCS in a reduced-size LT pig model and confirmed the presence of serum markers of oxidative tissue damage (malondialdehyde) and inflammatory cytokines (TNF-α, IL-1, IL-6) postoperatively [113]. In order to provide the complete picture, it would be of interest not only to measure the plasma levels of inflammatory markers, which were significantly lower in the NMP group, but also to quantify the same markers in the perfusates obtained from the device [113]. In addition, NMP promoted a significant reduction of molecules associated with apoptosis (cytochrome C, caspase 3) and cytokines and chemokines synthesis and secretion (NF-κB; p65) [113].…”

Opportunities for Therapeutic Intervention During Machine Perfusion

“…NMP has been used in a pig model of liver transplantation, simulating in-vivo liver resection and improving preservation. This strategy resulted in better post-transplantation outcomes when compared with the outcomes of livers that underwent reduction in SCS [56]. There have been reports of hepatocyte replication and biliary epithelial cell regeneration being detected during NMP [57, 58], and one can imagine also growing livers during NMP to either jumpstart the growth of a small liver prior to transplantation or a longer-term perfusion actually increasing the size of a small segment prior to transplantation.…”