Updates in Surgery

, Volume 66, Issue 2, pp 101–108 | Cite as

Perfusion machines for liver transplantation: technology and multifunctionality

Review Article


The reliability of machine perfusion (alternative to static cold storage) for the preservation of liver for transplantation has been well investigated in experimental models, by taking into account the temperature, oxygenation, flow, pressure, and settings of the machine or proposed circuit. Machine perfusion is considered by many researchers as a valid method for preserving organs. While circuits or machines for preservation have been described, no agreement has been reached concerning how these devices should be developed. The machines proposed to date are considered here to identify the technical and functional features necessary for a machine to have multifunctionality and adaptability to cater all the needs of preservation, according to the type and features of the liver to be transplanted, including marginal livers. The need to establish a uniform method for the use of this machine is also emphasized, to achieve a clinical protocol for its use.


Preservation of liver Machine perfusion Hyperbaric oxygen Thermal conservation 



Hypothermic machine perfusion


Machine perfusion


Non-heartbeating donor


Donation after circulatory determination of death


Simple cold storage



This study was supported by a grant from Fondazione Cassa di Risparmio of the Republic of San Marino (RSM) and Fondazione Cassa di Risparmio of Ferrara (Italy).

Conflict of interest

The author has no conflict of interest.


  1. 1.
    Slapak M, Wigmore RA, Mac Lean LD (1967) Twenty-four hour liver preservation by use of continuous pulsatile perfusion and hyperbaric oxygen. Transplantation 5:1154–1158PubMedCrossRefGoogle Scholar
  2. 2.
    Belzer FO, Ashby BS, Gulyassy PF et al (1968) Successful seventeen-hour preservation and transplantation of human-cadaver kidney. N Engl J Med 278:608–610PubMedCrossRefGoogle Scholar
  3. 3.
    Starzl TE, Groth CG, Brettschneider L et al (1968) Orthotopic homotransplantation of the human liver. Ann Surg 168:392–415PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Brettschneider L, Bell PR, Martin AJ Jr et al (1969) Conservation of the liver. Transpl Proc 1:132–137Google Scholar
  5. 5.
    D’Alessandro AM, Southard JH, Kalayoglu M et al (1986) Comparison of cold storage and perfusion of dog livers on function of tissue slices. Cryobiology 23:161–167PubMedCrossRefGoogle Scholar
  6. 6.
    Pienaar BH, Lindell SL, Van Gulik T, Southard JH et al (1990) Seventy-two hour preservation of the canine liver by machine perfusion. Transplantation 49(2):258–260 Google Scholar
  7. 7.
    Yamamoto N, Konishi Y, Wakashiro S et al (1991) Seventy-two-hour preservation of porcine liver by continuous hypothermic perfusion with UW solution in comparison with simple cold storage. J Surg Res 51:288–292PubMedCrossRefGoogle Scholar
  8. 8.
    Mendes-Braz M, Elias-Miró M, Jiménez-Castro MB, et al (2012) The current state of knowledge of hepatic ischemia-reperfusion injury based on its study in experimental models. J Biomed Biotechnol. Art ID. 298657Google Scholar
  9. 9.
    Guibert EE, Petrenko AY, Balaban CL et al (2011) Organ preservation: current concepts and new strategies for the next decade. Transfus Med Hemother 38:125–142PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Monbaliu D, Brassil J (2010) Machine perfusion of the liver: past, present and future. Curr Opin Organ Transpl 15:160–166CrossRefGoogle Scholar
  11. 11.
    Taylor MJ, Baicu SC (2010) Current state of hypothermic machine perfusion preservation of organs: the clinical perspective. Cryobiology 60:S20–S35PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    García-Valdecasas Salgado JC (2000) Non beating heart donors as a possible source for liver transplantation. Acta Chir Belg 100:268–271Google Scholar
  13. 13.
    van der Plaats A, t’Hart NA, Verkerke GJ et al (2004) Hypothermic machine preservation in liver transplantation revisited: concepts and criteria in the new millennium. Ann Biomed Eng 32:623–631PubMedCrossRefGoogle Scholar
  14. 14.
    McAnulty JF (2010) Hypothermic organ preservation by static storage methods: current status and a view to the future. Cryobiology 60:S13–S19PubMedCrossRefGoogle Scholar
  15. 15.
    Henry SD, Nachber E, Tulipan J et al (2012) Hypothermic machine preservation reduces molecular markers of ischemia/reperfusion injury in human liver transplantation. Am J Transpl 12(9):2477–2486CrossRefGoogle Scholar
  16. 16.
    Lee CY, Zhang JX, Jones JW Jr et al (2002) Functional recovery of preserved livers following warm ischemia: improvement by machine perfusion preservation. Transplantation 74:944–951PubMedCrossRefGoogle Scholar
  17. 17.
    Bessems M, Doorschodt BM, Kolkert JL et al (2007) Preservation of steatotic livers: a comparison between cold storage and machine perfusion preservation. Liver Transpl 13:497–504PubMedCrossRefGoogle Scholar
  18. 18.
    Vekemans K, Liu Q, Pirenne J et al (2008) Artificial circulation of the liver: machine perfusion as a preservation method in liver transplantation. Anat Rec (Hoboken) 291:735–740CrossRefGoogle Scholar
  19. 19.
    Scaduto RC Jr, Grotyohann LW (1999) Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J 76:469–477PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Dutkowski P, Graf R, Clavien PA (2006) Rescue of the cold preserved rat liver by hypothermic oxygenated machine perfusion. Am J Transpl 6:903–912CrossRefGoogle Scholar
  21. 21.
    Rubbini M, Longobardi P, Rimessi A et al (2007) Una nuova macchina trasportabile per la conservazione mediante perfusione iperbarica ossigenata del fegato da trapiantare. Chir Ital 59:723–734PubMedGoogle Scholar
  22. 22.
    Moers C, Smits JM, Maathuis MH et al (2009) Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 360:7–19PubMedCrossRefGoogle Scholar
  23. 23.
    Guarrera JV, Henry SD, Samstein B et al (2010) Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transpl 10:372–381CrossRefGoogle Scholar
  24. 24.
    Guarrera JV, Estevez J, Boykin J et al (2005) Hypothermic machine perfusion of liver grafts for transplantation: technical development in human discard and miniature swine models. Transpl Proc 37:323–325CrossRefGoogle Scholar
  25. 25.
    Dutkowski P, Furrer K, Tian Y, et al (2006) Novel short-term hypothermic oxygenated perfusion (HOPE) system prevents injury in rat liver graft from non-heart beating donor. Ann Surg 244:968–976, discussion 976–977Google Scholar
  26. 26.
    Reddy S, Greenwood J, Maniakin N et al (2005) Non-heart-beating donor porcine livers: the adverse effect of cooling. Liver Transpl 11:35–38PubMedCrossRefGoogle Scholar
  27. 27.
    Maathuis MH, Leuvenink HG, Ploeg RJ (2007) Perspectives in organ preservation. Transplantation 83:1289–1298PubMedCrossRefGoogle Scholar
  28. 28.
    Xu H, Lee CY, Clemens MG et al (2004) Pronlonged hypothermic machine perfusion preserves hepatocellular function but potentiates endothelial cell dysfunction in rat livers. Transplantation 77:1676–1682PubMedCrossRefGoogle Scholar
  29. 29.
    de Rougemont O, Lehmann K, Clavien PA (2009) Preconditioning, organ preservation, and postconditioning to prevent ischemia-reperfusion injury to the liver. Liver Transpl 15:1172–1182PubMedCrossRefGoogle Scholar
  30. 30.
    Monbaliu D, Heedfeld V, Liu Q et al (2011) Hypothermic machine perfusion of the liver: is it more complex than for the kidney? Transpl Proc 43:3445–3450CrossRefGoogle Scholar
  31. 31.
    Fuller BJ, Pegg DE (1976) The assessment of renal preservation by normothermic bloodless perfusion. Cryobiology 13:177–184PubMedCrossRefGoogle Scholar
  32. 32.
    McLaren AJ, Friend PJ (2003) Trends in organ preservation. Transpl Int 16:701–708PubMedCrossRefGoogle Scholar
  33. 33.
    Schön MR, Kollmar O, Wolf S et al (2001) Liver transplantation after organ preservation with normothermic extracorporeal perfusion. Ann Surg 233:114–123PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Butler AJ, Rees MA, Wight DG et al (2002) Successful extracorporeal porcine liver perfusion for 72 hr. Transplantation 73:1212–1218PubMedCrossRefGoogle Scholar
  35. 35.
    Brockmann J, Reddy S, Coussios C et al (2009) Normothermic perfusion: a new paradigm for organ preservation. Ann Surg 250:1–6PubMedCrossRefGoogle Scholar
  36. 36.
    García-Valdecasas JC, Fondevila C (2010) In-vivo normothermic recirculation: an update. Curr Opin Organ Transpl 15:173–176CrossRefGoogle Scholar
  37. 37.
    Vogel T, Brockmann JG, Friend PJ (2010) Ex-vivo normothermic liver perfusion: an update. Curr Opin Organ Transpl 15:167–172CrossRefGoogle Scholar
  38. 38.
    Hessheimer AJ, Fondevila C, García-Valdecasas JC (2012) Extracorporeal machine liver perfusion: are we warming up? Curr Opin Organ Transpl 17:143–147CrossRefGoogle Scholar
  39. 39.
    Xu H, Berendsen T, Kim K et al (2012) Excorporeal normothermic machine perfusion resuscitates pig DCD livers with extended warm ischemia. J Surg Res 173:e83–e88PubMedCentralPubMedCrossRefGoogle Scholar
  40. 40.
    St Peter SD, Imber CJ, Lopez I, et al (2002) Extended preservation of non-heart-beating donor livers with normothermic machine perfusion. Br J Surg 89:609–616Google Scholar
  41. 41.
    Nui A, Katsuramaki T, Kikuchi H et al (2006) The functional integrity of a normothermic perfusion system using artificial blood in pig liver. J Surg Res 131:189–198PubMedCrossRefGoogle Scholar
  42. 42.
    Vairetti M, Ferrigno A, Rizzo V et al (2007) Subnormothermic machine perfusion protects against rat liver preservation injury: a comparative evaluation with conventional cold storage. Transpl Proc 39:1765–1767CrossRefGoogle Scholar
  43. 43.
    Olschewski P, Gass P, Ariyakhagorn V et al (2010) The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers. Cryobiology 60:337–343PubMedCrossRefGoogle Scholar
  44. 44.
    Ferrigno A, Rizzo V, Boncompagni E et al (2011) Machine perfusion at 20°C reduces preservation damage to livers from non-heart beating donors. Cryobiology 62:152–158PubMedCrossRefGoogle Scholar
  45. 45.
    Tolboom H, Izamis ML, Sharma N et al (2012) Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation. J Surg Res 175:149–156PubMedCrossRefGoogle Scholar
  46. 46.
    Vairetti M, Ferrigno A, Carlucci F et al (2009) Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase? Liver Transpl 15:20–29PubMedCrossRefGoogle Scholar
  47. 47.
    Gringeri E, Bonsignore P, Bassi D, et al (2012) Subnormothermic machine perfusion for non-heart- beating donor liver grafts preservation in a swinw model : a new strategy to increase the donor pool? Transpl Proc 44(7):2026–2028Google Scholar
  48. 48.
    Fujita S, Hamamoto I, Nakamura K et al (1993) Evaluation of oxygen necessity during hypothermic liver perfusion. Arch Jpn Chir 62:228–240Google Scholar
  49. 49.
    Vekemans K, Liu Q, Brassil J et al (2007) Influence of flow and addition of oxygen during porcine liver hypothermic machine perfusion. Transpl Proc 39:2647–2651CrossRefGoogle Scholar
  50. 50.
    Lüer B, Koetting M, Efferz P et al (2010) Role of oxygen during hypothermic machine perfusion preservation of the liver. Transpl Int 23:944–950PubMedGoogle Scholar
  51. 51.
    Wang CC, Wang SH, Lin CC et al (2005) Liver transplantation from an uncontrolled non-heart-beating donor maintained on extracorporeal membrane oxygenation. Transpl Proc 37:4331–4333CrossRefGoogle Scholar
  52. 52.
    Minor T, Pütter C, Gallinat A et al (2011) Oxygen persufflation as adjunct in liver preservation (OPAL): study protocol for a randomized controlled trial. Trials 12:234PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Suszynski TM, Rizzari MD, Scott WE 3rd et al (2012) Persufflation (or gaseous oxygen perfusion) as a method of organ preservation. Cryobiology 64:125–143PubMedCentralPubMedCrossRefGoogle Scholar
  54. 54.
    Dutkowski P, de Rougemont O, Clavien PA (2008) Machine perfusion for ‘marginal’ liver grafts. Am J Transpl 8:917–924CrossRefGoogle Scholar
  55. 55.
    Bessems M, ‘t Hart NA, Tolba R et al (2006) The isolated perfused rat liver: standardization of a time-honoured model. Lab Anim 40:236–246PubMedCrossRefGoogle Scholar
  56. 56.
    Bessems M, Doorschodt BM, van Marle J et al (2005) Improved machine perfusion preservation of the non-heart-beating donor rat liver using Polysol: a new machine perfusion preservation solution. Liver Transpl 11:1379–1388PubMedCrossRefGoogle Scholar
  57. 57.
    Jaeschke H, Woolbright BL (2012) Current strategies to minimize hepatic ischemia-reperfusion injury by targeting reactive oxygen species. Transpl Rev (Orlando) 26:103–114CrossRefGoogle Scholar
  58. 58.
    Wszola M, Kwiatkowski A, Latek M et al (2009) Long term medical and economical benefit of machine perfusion (MP) kidney storage in comparison to cold storage (CS). Ann Transpl 14:24–29Google Scholar
  59. 59.
    Groen H, Moers C, Smits JM et al (2012) Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation. Am J Transpl 12(7):1824–1830CrossRefGoogle Scholar
  60. 60.
    Fondevila C, Hessheimer AJ, Maathuis MH et al (2011) Superior preservation of DCD livers with continuous normothermic perfusion. Ann Surg 254:1000–1007PubMedCrossRefGoogle Scholar
  61. 61.
    van der Plaats A, Maathuis MH, ‘T Hart NA et al (2006) The Groningen hypothermic liver perfusion pump: functional evaluation of a new machine perfusion system. Ann Biomed Eng 34:1924–1934PubMedCrossRefGoogle Scholar
  62. 62.
    Post IC, Dirkes MC, Heger M et al (2012) Optimal flow and pressure management in machine perfusion systems for organ preservation. Ann Biomed Eng 40(12):2698–2707PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2013

Authors and Affiliations

  1. 1.Department of SurgeryUniversity of FerraraFerraraItaly

Personalised recommendations