Liver machine perfusion (MP) has emerged as a promising organ preservation modality. Recent studies have shown that the addition of the kidneys to the circuit improves the biochemical environment and could benefit liver preservation. The aim of this study was to explore the technical and anatomical feasibility of en bloc liver–pancreas–kidney MP. We also examined the safety of ex vivo perfusion with a nonoxygen carrier solution and its effects on acid–base and metabolic parameters using this novel multivisceral perfusion platform.
Methods:
Five multivisceral allografts, including liver, pancreas, duodenum, and kidney, were perfused for 4 h with acellular perfusate. Hemodynamic and laboratory data were evaluated throughout the experiment.
Results:
No system failure was reported. There were minimal changes in the acid–base parameters during the experiment. Lactate and glucose levels were stable throughout hypothermic perfusion. There was a mild increase in liver function parameters in the last hour of hypothermic perfusion. No changes in creatinine levels were observed throughout the study. The urine output increased steadily during the experiment, with an average of 155.6 mL/h.
Conclusion:
We described an innovative multivisceral MP technique that could be further used as a platform for physiological studies and targeted therapeutic interventions. Further investigations are necessary to evaluate this ex vivo perfusion technique and provide insights into the feasibility of hypothermic acellular multivisceral MP in clinical scenarios.
DetelichDMarkmannJF.The dawn of liver perfusion machines. Curr Opin Organ Transplant2018; 23(2): 151–161.
2.
LongchampANakamuraTUygunK, et al. Role of machine perfusion in liver transplantation. Surg Clin North Am2024; 104(1): 45–65.
3.
DutkowskiPde RougemontOClavienPA.Machine perfusion for 'marginal' liver grafts. Am J Transplant2008; 8(5): 917–924.
4.
ChungWYGravanteGAl-LeswasD, et al. The development of a multiorgan ex vivo perfused model: results with the porcine liver-kidney circuit over 24 hours. Artif Organs2013; 37(5): 457–466.
5.
ChungWYGravanteGAl-LeswasD, et al. The autologous normothermic ex vivo perfused porcine liver-kidney model: improving the circuit’s biochemical and acid-base environment. Am J Surg2012; 204(4): 518–526.
6.
ChungWYGravanteGEltweriA, et al. The “kidney-liver” multiorgan ex vivo perfused model improves the circuit's biochemical milieu during perfusion compared to the “liver-kidney” counterpart. J Artif Organs2015; 18(2): 151–161.
7.
HeXJiFZhangZ, et al. Combined liver-kidney perfusion enhances protective effects of normothermic perfusion on liver grafts from donation after cardiac death. Liver Transplant2018; 24(1): 67–79.
8.
LiJJiaJHeN, et al. Combined kidney‑liver perfusion enhances the proliferation effects of hypothermic perfusion on liver grafts via upregulation of IL‑6/Stat3 signaling. Mol Med Rep2019; 20(2): 1663–1671.
9.
CruzRJJr.CostaGBondG, et al. Modified "liver-sparing" multivisceral transplant with preserved native spleen, pancreas, and duodenum: technique and long-term outcome. J Gastrointest Surg2010; 14(11): 1709–1721.
10.
Op den DriesSSuttonMEKarimianN, et al. Hypothermic oxygenated machine perfusion prevents arteriolonecrosis of the peribiliary plexus in pig livers donated after circulatory death. PLoS One2014; 9(2): e88521.
11.
DirkesMCPostICHegerM, et al. A novel oxygenated machine perfusion system for preservation of the liver. Artif Organs2013; 37(8): 719–724.
12.
CruzRJJr.CostaGBondGJ, et al. Modified multivisceral transplantation with spleen-preserving pancreaticoduodenectomy for patients with familial adenomatous polyposis "Gardner's Syndrome". Transplantation2011; 91(12): 1417–1423.
13.
Abu-ElmagdKBondGReyesJ, et al. Intestinal transplantation: a coming of age. Adv Surg2002; 36: 65–101.
14.
JomaaAGurusamyKSiriwardanaPN, et al. Does hypothermic machine perfusion of human donor livers affect risks of sinusoidal endothelial injury and microbial infection? A feasibility study assessing flow parameters, sterility, and sinusoidal endothelial ultrastructure. Transplant Proc2013; 45(5): 1677–1683.
15.
SchlegelAde RougemontOGrafR, et al. Protective mechanisms of end-ischemic cold machine perfusion in DCD liver grafts. J Hepatol2013; 58(2): 278–286.
16.
van der PlaatsAMaathuisMHNATH, et al. The Groningen hypothermic liver perfusion pump: functional evaluation of a new machine perfusion system. Ann Biomed Eng2006; 34(12): 1924–1934.
17.
HartNAvan der PlaatsALeuveninkHG, et al. Hypothermic machine perfusion of the liver and the critical balance between perfusion pressures and endothelial injury. Transplant Proc2005; 37(1): 332–334.
18.
FontesPLopezRvan der PlaatsA, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions. Am J Transpl2015; 15(2): 381–394.
19.
NassarALiuQFariasK, et al. Ex vivo normothermic machine perfusion is safe, simple, and reliable: results from a large animal model. Surg Innov2015; 22(1): 61–69.
20.
TulipanJEStoneJSamsteinB, et al. Molecular expression of acute phase mediators is attenuated by machine preservation in human liver transplantation: preliminary analysis of effluent, serum, and liver biopsies. Surgery2011; 150(2): 352–360.
21.
BhogalRHMirzaDFAffordSC, et al. Biomarkers of liver injury during transplantation in an era of machine perfusion. Int J Mol Sci2020; 21(5): 1578.
22.
HenrySDNachberETulipanJ, et al. Hypothermic machine preservation reduces molecular markers of ischemia/reperfusion injury in human liver transplantation. Am J Transplant2012; 12(9): 2477–2486.
23.
GuarreraJVHenrySDSamsteinB, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant2010; 10(2): 372–381.
24.
ReilingJLockwoodDSSimpsonAH, et al. Urea production during normothermic machine perfusion: price of success?Liver Transplant2015; 21(5): 700–703.
25.
Linares-CervantesIEcheverriJClelandS, et al. Predictor parameters of liver viability during porcine normothermic ex situ liver perfusion in a model of liver transplantation with marginal grafts. Am J Transplant2019; 19(11): 2991–3005.
26.
LiuQVekemansKIaniaL, et al. Assessing warm ischemic injury of pig livers at hypothermic machine perfusion. J Surg Res2014; 186(1): 379–389.
27.
MonbaliuDVekemansKDe VosR, et al. Hemodynamic, biochemical, and morphological characteristics during preservation of normal porcine livers by hypothermic machine perfusion. Transplant Proc2007; 39(8): 2652–2658.
28.
SchonMRKollmarOWolfS, et al. Liver transplantation after organ preservation with normothermic extracorporeal perfusion. Ann Surg2001; 233(1): 114–123.
29.
EckhauserFKnolJAPorter-FinkV, et al. Ex vivo normothermic hemoperfusion of the canine pancreas: applications and limitations of a modified experimental preparation. J Surg Res1981; 31(1): 22–37.
30.
BuchwaldJEXuJBozorgzadehA, et al. Therapeutics administered during ex vivo liver machine perfusion: an overview. World J Transplant2020; 10(1): 1–14.
31.
EcheverriJGoldaracenaNKathsJM, et al. Comparison of BQ123, epoprostenol, and verapamil as vasodilators during normothermic ex vivo liver machine perfusion. Transplantation2018; 102(4): 601–608.
32.
BankerABhattNRaoPS, et al. A review of machine perfusion strategies in liver transplantation. J Clin Exp Hepatol2023; 13(2): 335–349.
33.
van BeekumCJVilzTOGlowkaTR, et al. Normothermic Machine Perfusion (NMP) of the liver - current status and future perspectives. Ann Transplant2021; 26: e931664.
34.
WatsonCJEGauravRButlerAJ.Current techniques and indications for machine perfusion and regional perfusion in deceased donor liver transplantation. J Clin Exp Hepatol2024; 14(2): 101309.
