Abstract
Background
Machine perfusion (MP) in solid organ transplantation has been a topic of variable importance for decades. At the dawn of organ transplantation, MP was one of the standard techniques for preservation; today’s gold standard for organ preservation for transplantation is cold storage (CS). The outcome after transplantation of solid organs has tremendously improved over the last five decades. MP has been continuously under investigation and may be an option for organ preservation in selected cases; however, there is only little evidence from clinical trials that can be used to advocate for MP as a routine organ preservation method.
Methods
This article reviews the current knowledge on MP in the field of solid organ transplantation with special focus on findings from clinical trials.
Conclusion
Especially in heart and lung transplantation, MP seems to be a promising tool to improve postoperative outcome, but a general evidence-based recommendation for or against an application of MP cannot be given due to the lack of the highest level of clinical evidence. Gold standards such as CS should not be left behind without good reason. Randomized clinical trials are desperately needed to further improve outcome and for better understanding of the underlying pathophysiological mechanisms.
Similar content being viewed by others
References
Le Gallois CJJ (1812) Expériences sur le principe de la vie: notamment sur celui des mouvements du coeur, et sur le siége de ce principe. D’Hautel
Carrel A, Lindbergh CA (1935) The culture of whole organs. Science 81(2112):621–623. doi:10.1126/science.81.2112.621
Malinin TI (1996) Remembering Alexis Carrel and Charles A. Lindbergh. Tex Heart Inst J 23(1):28–35
Moore TC, English TS, Berne TV (1974) Machine preservation of 302 human cadaveric kidneys for transplantation. Surg Gynecol Obstet 138(2):239–243
Stephenson TP, Hendry WF, Ward JP, Wickham JE (1975) Continuous perfusion of human cadaveric kidneys for transplantation. Br J Urol 47(1):37–44
Stephenson TP, O’Donoghue EP, Hendry WF, Wickham JE (1973) Preservation of human kidneys for transplantation: preliminary results with a Gambro perfusion machine. Br Med J 1(5850):379–381
Opelz G, Terasaki PI (1976) Kidney preservation: perfusion versus cold storage—1975. Transplant Proc 8(1):121–125
Opelz G, Terasaki PI (1982) Advantage of cold storage over machine perfusion for preservation of cadaver kidneys. Transplantation 33(1):64–68
Aberg F, Isoniemi H, Hockerstedt K (2011) Long-term results of liver transplantation. Scand J Surg 100(1):14–21
Singh S, Watt KD (2012) Long-term medical management of the liver transplant recipient: what the primary care physician needs to know. Mayo Clin Proc 87(8):779–790. doi:10.1016/j.mayocp.2012.02.021
Bond M, Pitt M, Akoh J, Moxham T, Hoyle M, Anderson R (2009) The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model. Health Technol Assess 13 (38):iii–iv, xi–xiv, 1–156. doi:10.3310/hta13380.
Opelz G, Dohler B (2007) Multicenter analysis of kidney preservation. Transplantation 83(3):247–253. doi:10.1097/01.tp.0000251781.36117.27
Wight JP, Chilcott JB, Holmes MW, Brewer N (2003) Pulsatile machine perfusion vs. cold storage of kidneys for transplantation: a rapid and systematic review. Clin Transplant 17(4):293–307
Belzer FO, Ashby BS, Huang JS, Dunphy JE (1968) Etiology of rising perfusion pressure in isolated organ perfusion. Ann Surg 168(3):382–391
Jochmans I, Pirenne J (2011) Graft quality assessment in kidney transplantation: not an exact science yet! Curr Opin Organ Transplant 16(2):174–179. doi:10.1097/MOT.0b013e3283446b31
Jochmans I, Moers C, Smits JM, Leuvenink HG, Treckmann J, Paul A, Rahmel A, Squifflet JP, van Heurn E, Monbaliu D, Ploeg RJ, Pirenne J (2011) The prognostic value of renal resistance during hypothermic machine perfusion of deceased donor kidneys. Am J Transplant 11(10):2214–2220. doi:10.1111/j.1600-6143.2011.03685.x
Nagelschmidt M, Minor T, Gallinat A, Moers C, Jochmans I, Pirenne J, Ploeg RJ, Paul A, Treckmann J (2012) Lipid peroxidation products in machine perfusion of older donor kidneys. J Surg Res. doi:10.1016/j.jss.2012.04.071
Tulipan JE, Stone J, Samstein B, Kato T, Emond JC, Henry SD, Guarrera JV (2011) Molecular expression of acute phase mediators is attenuated by machine preservation in human liver transplantation: preliminary analysis of effluent, serum, and liver biopsies. Surgery 150(2):352–360. doi:10.1016/j.surg.2011.06.003
Patel SK, Pankewycz OG, Nader ND, Zachariah M, Kohli R, Laftavi MR (2012) Prognostic utility of hypothermic machine perfusion in deceased donor renal transplantation. Transplant Proc 44(7):2207–2212. doi:10.1016/j.transproceed.2012.07.129
Moers C, Pirenne J, Paul A, Ploeg RJ (2012) Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 366(8):770–771. doi:10.1056/NEJMc1111038
Warnecke G, Moradiellos J, Tudorache I, Kuhn C, Avsar M, Wiegmann B, Sommer W, Ius F, Kunze C, Gottlieb J, Varela A, Haverich A (2012) Normothermic perfusion of donor lungs for preservation and assessment with the Organ Care System Lung before bilateral transplantation: a pilot study of 12 patients. Lancet. doi:10.1016/S0140-6736(12)61344-0
Alijani MR, Cutler JA, DelValle CJ, Morres DN, Fawzy A, Pechan BW, Helfrich GB (1985) Single-donor cold storage versus machine perfusion in cadaver kidney preservation. Transplantation 40(6):659–661
Guarrera JV, Henry SD, Chen SW, Brown T, Nachber E, Arrington B, Boykin J, Samstein B, Brown RS Jr, Emond JC, Lee HT (2011) Hypothermic machine preservation attenuates ischemia/reperfusion markers after liver transplantation: preliminary results. J Surg Res 167(2):e365–e373. doi:10.1016/j.jss.2010.01.038
Guarrera JV, Polyak M, O’Mar Arrington B, Kapur S, Stubenbord WT, Kinkhabwala M (2004) Pulsatile machine perfusion with Vasosol solution improves early graft function after cadaveric renal transplantation. Transplantation 77(8):1264–1268
Moers C, Smits JM, Maathuis MH, Treckmann J, van Gelder F, Napieralski BP, van Kasterop-Kutz M, van der Heide JJ, Squifflet JP, van Heurn E, Kirste GR, Rahmel A, Leuvenink HG, Paul A, Pirenne J, Ploeg RJ (2009) Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med 360(1):7–19. doi:10.1056/NEJMoa0802289
van der Vliet JA, Kievit JK, Hene RJ, Hilbrands LB, Kootstra G (2001) Preservation of non-heart-beating donor kidneys: a clinical prospective randomised case–control study of machine perfusion versus cold storage. Transplant Proc 33(1–2):847
Watson CJ, Wells AC, Roberts RJ, Akoh JA, Friend PJ, Akyol M, Calder FR, Allen JE, Jones MN, Collett D, Bradley JA (2010) Cold machine perfusion versus static cold storage of kidneys donated after cardiac death: a UK multicenter randomized controlled trial. Am J Transplant 10(9):1991–1999. doi:10.1111/j.1600-6143.2010.03165.x
Marshall VC, Ross H, Scott DF, McInnes S, Thomson N, Atkins RC, Mathew TH, Kincaid-Smith PS (1977) Preservation of cadaver of renal allografts: comparison of ice storage and machine perfusion. Med J Aust 2(11):353–356
Sheil AG, Drummond JM, Rogers JH, Boulas J, May J, Storey BG (1975) A controlled clinical trial of machine perfusion of cadaveric donor renal allografts. Lancet 2(7929):287–290
McCurry K, Jeevanandam V, Mihaljevic T, Couper G, Elanwar M, Saleh H, Ardehali A (2008) The 1-year follow-up results of the PROTECT patient population using the organ care system. J Heart Lung Transplant 27 (2). doi:10.1016/j.healun.2007.11.302
McCurry K, Jeevanandam V, Mihaljevic T, Couper G, Elanwar M, Saleh H, Ardehali A (2008) Prospective multi-center safety and effectiveness evaluation of the organ care system device for cardiac use (PROCEED). J Heart Lung Transplant 27(2). doi:10.1016/j.healun.2007.11.302
Lee CY, Mangino MJ (2009) Preservation methods for kidney and liver. Organogenesis 5(3):105–112
Monbaliu D, Heedfeld V, Liu Q, Wylin T, van Pelt J, Vekemans K, Pirenne J (2011) Hypothermic machine perfusion of the liver: is it more complex than for the kidney? Transplant Proc 43(9):3445–3450. doi:10.1016/j.transproceed.2011.09.033
Treckmann J, Moers C, Smits JM, Gallinat A, Maathuis MH, van Kasterop-Kutz M, Jochmans I, Homan van der Heide JJ, Squifflet JP, van Heurn E, Kirste GR, Rahmel A, Leuvenink HG, Pirenne J, Ploeg RJ, Paul A (2011) Machine perfusion versus cold storage for preservation of kidneys from expanded criteria donors after brain death. Transpl Int 24(6):548–554. doi:10.1111/j.1432-2277.2011.01232.x
Buchanan PM, Lentine KL, Burroughs TE, Schnitzler MA, Salvalaggio PR (2008) Association of lower costs of pulsatile machine perfusion in renal transplantation from expanded criteria donors. Am J Transplant 8(11):2391–2401. doi:10.1111/j.1600-6143.2008.02412.x
Post IC, Dirkes MC, Heger M, Bezemer R, van ’t Leven J, van Gulik TM (2012) Optimal flow and pressure management in machine perfusion systems for organ preservation. Ann Biomed Eng. doi:10.1007/s10439-012-0601-9
Groen H, Moers C, Smits JM, Treckmann J, Monbaliu D, Rahmel A, Paul A, Pirenne J, Ploeg RJ, Buskens E (2012) Cost-effectiveness of hypothermic machine preservation versus static cold storage in renal transplantation. Am J Transplant 12(7):1824–1830. doi:10.1111/j.1600-6143.2012.04030.x
Liu Q, Bruns H, Schultze D, Xue Y, Zorn M, Flechtenmacher C, Straub BK, Rauen U, Schemmer P (2012) HTK-N, a modified HTK solution, decreases preservation injury in a model of microsteatotic rat liver transplantation. Langenbeck’s Arch Surg 397(8):1323–1331. doi:10.1007/s00423-012-1022-9
Cannata A, Botta L, Colombo T, Russo CF, Taglieri C, Bruschi G, Merlanti B, Frigerio M, Martinelli L (2012) Does the cardioplegic solution have an effect on early outcomes following heart transplantation? Eur J Cardiothorac Surg 41(4):e48–e52. doi:10.1093/ejcts/ezr321, discussion e52–43
de Boer J, De Meester J, Smits JM, Groenewoud AF, Bok A, van der Velde O, Doxiadis II, Persijn GG (1999) Eurotransplant randomized multicenter kidney graft preservation study comparing HTK with UW and Euro-Collins. Transpl Int 12(6):447–453
Loganathan S, Radovits T, Hirschberg K, Korkmaz S, Koch A, Karck M, Szabo G (2010) Effects of Custodiol-N, a novel organ preservation solution, on ischemia/reperfusion injury. J Thorac Cardiovasc Surg 139(4):1048–1056. doi:10.1016/j.jtcvs.2009.09.034
Pizanis N, Petrov A, Heckmann J, Wiswedel I, Wohlschlager J, de Groot H, Jakob H, Rauen U, Kamler M (2012) A new preservation solution for lung transplantation: evaluation in a porcine transplantation model. J Heart Lung Transplant 31(3):310–317. doi:10.1016/j.healun.2011.11.009
Stegemann J, Hirner A, Rauen U, Minor T (2010) Use of a new modified HTK solution for machine preservation of marginal liver grafts. J Surg Res 160(1):155–162. doi:10.1016/j.jss.2008.10.021
Polyak MM, Grosche A (2008) Comparison of Vasosol and University of Wisconsin solutions on early kidney function after 24 h of cold ischemia in a canine autotransplantation model. J Surg Res 150(2):255–260. doi:10.1016/j.jss.2007.11.727
Bae C, Henry SD, Guarrera JV (2012) Is extracorporeal hypothermic machine perfusion of the liver better than the ‘good old icebox’? Curr Opin Organ Transplant 17(2):137–142. doi:10.1097/MOT.0b013e328351083d
Vekemans K, van Pelt J, Komuta M, Wylin T, Heedfeld V, Detry O, Monbaliu D, Pirenne J (2011) Attempt to rescue discarded human liver grafts by end ischemic hypothermic oxygenated machine perfusion. Transplant Proc 43(9):3455–3459. doi:10.1016/j.transproceed.2011.09.029
Xu H, Berendsen T, Kim K, Soto-Gutierrez A, Bertheium F, Yarmush ML, Hertl M (2012) Excorporeal normothermic machine perfusion resuscitates pig DCD livers with extended warm ischemia. J Surg Res 173(2):e83–e88. doi:10.1016/j.jss.2011.09.057
Luer B, Koetting M, Efferz P, Minor T (2010) Role of oxygen during hypothermic machine perfusion preservation of the liver. Transpl Int 23(9):944–950. doi:10.1111/j.1432-2277.2010.01067.x
Saad S, Minor T (2008) Short-term resuscitation of predamaged donor livers by brief machine perfusion: the influence of temperature. Transplant Proc 40(10):3321–3326. doi:10.1016/j.transproceed.2008.06.058
Lauschke H, Olschewski P, Tolba R, Schulz S, Minor T (2003) Oxygenated machine perfusion mitigates surface antigen expression and improves preservation of predamaged donor livers. Cryobiology 46(1):53–60
Gringeri E, Bonsignore P, Bassi D, D’Amico FE, Mescoli C, Polacco M, Buggio M, Luisetto R, Boetto R, Noaro G, Ferrigno A, Boncompagni E, Freitas I, Vairetti MP, Carraro A, Neri D, Cillo U (2012) Subnormothermic machine perfusion for non-heart-beating donor liver grafts preservation in a Swine model: a new strategy to increase the donor pool? Transplant Proc 44(7):2026–2028. doi:10.1016/j.transproceed.2012.06.014
Fondevila C, Hessheimer AJ, Maathuis MH, Munoz J, Taura P, Calatayud D, Leuvenink H, Rimola A, Garcia-Valdecasas JC, Ploeg RJ (2012) Hypothermic oxygenated machine perfusion in porcine donation after circulatory determination of death liver transplant. Transplantation 94(1):22–29. doi:10.1097/TP.0b013e31825774d7
Shigeta T, Matsuno N, Obara H, Mizunuma H, Kanazawa H, Tanaka H, Fukuda A, Sakamoto S, Kasahara M, Uemoto S, Enosawa S (2012) Functional recovery of donation after cardiac death liver graft by continuous machine perfusion preservation in pigs. Transplant Proc 44(4):946–947. doi:10.1016/j.transproceed.2012.01.078
Bruns H, Watanpour I, Gebhard MM, Flechtenmacher C, Galli U, Schulze-Bergkamen H, Zorn M, Büchler MW, Schemmer P (2011) Glycine and taurine equally prevent fatty livers from Kupffer cell-dependent injury: an in vivo microscopy study. Microcirculation 18(3):205–213. doi:10.1111/j.1549-8719.2010.00078.x
Liang R, Bruns H, Kincius M, Lin T, Ludwig J, Dei-Anane G, Guan X, Gebhard MM, Büchler MW, Schemmer P (2009) Danshen protects liver grafts from ischemia/reperfusion injury in experimental liver transplantation in rats. Transpl Int 22(11):1100–1109. doi:10.1111/j.1432-2277.2009.00925.x
Schindler G, Kincius M, Liang R, Backhaus J, Zorn M, Flechtenmacher C, Gebhard MM, Büchler MW, Schemmer P (2009) Fundamental efforts toward the development of a therapeutic cocktail with a manifold ameliorative effect on hepatic ischemia/reperfusion injury. Microcirculation 16(7):593–602. doi:10.1080/10739680903110779
Florack G, Sutherland DE, Heil J, Squifflet JP, Najarian JS (1983) Preservation of canine segmental pancreatic autografts: cold storage versus pulsatile machine perfusion. J Surg Res 34(5):493–504
Leeser DB, Bingaman AW, Poliakova L, Shi Q, Gage F, Bartlett ST, Farney AC (2004) Pulsatile pump perfusion of pancreata before human islet cell isolation. Transplant Proc 36(4):1050–1051. doi:10.1016/j.transproceed.2004.04.041
Taylor MJ, Baicu S, Greene E, Vazquez A, Brassil J (2010) Islet isolation from juvenile porcine pancreas after 24-h hypothermic machine perfusion preservation. Cell Transplant 19(5):613–628. doi:10.3727/096368910X486316
Taylor MJ, Baicu S, Leman B, Greene E, Vazquez A, Brassil J (2008) Twenty-four-hour hypothermic machine perfusion preservation of porcine pancreas facilitates processing for islet isolation. Transplant Proc 40(2):480–482. doi:10.1016/j.transproceed.2008.01.004
Hamed A, Tsui S, Huber J, Lin R, Poggio EC, Ardehali A (2009) Serum lactate is a highly sensitive and specific predictor of post cardiac transplant outcomes using the organ care system. J Heart Lung Transplant 28(2):S71. doi:10.1016/j.healun.2008.11.025
Yeter R, Hübler M, Pasic M, Hetzer R, Knosalla C (2011) Organ preservation with the organ care system. Appl Cardiopulm Pathophysiol 15:207–212
Steen S, Sjoberg T, Pierre L, Liao Q, Eriksson L, Algotsson L (2001) Transplantation of lungs from a non-heart-beating donor. Lancet 357(9259):825–829. doi:10.1016/S0140-6736(00)04195-7
Cypel M, Keshavjee S (2012) The clinical potential of ex vivo lung perfusion. Expert Rev Respir Med 6(1):27–35. doi:10.1586/ers.11.93
Cypel M, Yeung JC, Liu M, Anraku M, Chen F, Karolak W, Sato M, Laratta J, Azad S, Madonik M, Chow CW, Chaparro C, Hutcheon M, Singer LG, Slutsky AS, Yasufuku K, de Perrot M, Pierre AF, Waddell TK, Keshavjee S (2011) Normothermic ex vivo lung perfusion in clinical lung transplantation. N Engl J Med 364(15):1431–1440. doi:10.1056/NEJMoa1014597
Cypel M, Liu M, Rubacha M, Yeung JC, Hirayama S, Anraku M, Sato M, Medin J, Davidson BL, de Perrot M, Waddell TK, Slutsky AS, Keshavjee S (2009) Functional repair of human donor lungs by IL-10 gene therapy. Sci Transl Med 1(4):4ra9. doi:10.1126/scitranslmed.3000266
Hajjar G, Toledo-Pereyra LH, Mackenzie GH (1986) Effect of 24-hour preservation with oxygen free radical scavengers on isolated-perfused canine heart-lungs. P R Health Sci J 5(1):19–25
Nakajima D, Chen F, Yamada T, Sakamoto J, Osumi A, Fujinaga T, Shoji T, Sakai H, Bando T, Date H (2011) Hypothermic machine perfusion ameliorates ischemia-reperfusion injury in rat lungs from non-heart-beating donors. Transplantation 92(8):858–863. doi:10.1097/TP.0b013e31822d8778
Nakajima D, Chen F, Okita K, Motoyama H, Hijiya K, Ohsumi A, Sakamoto J, Yamada T, Sato M, Aoyama A, Bando T, Date H (2012) Reconditioning lungs donated after cardiac death using short-term hypothermic machine perfusion. Transplantation. doi:10.1097/TP.0b013e31826f632e
Guan X, Dei-Anane G, Bruns H, Chen J, Nickkholgh A, Liang R, Gross ML, Kern M, Ludwig J, Büchler MW, Schemmer P (2009) Danshen protects kidney grafts from ischemia/reperfusion injury after experimental transplantation. Transpl Int 22(2):232–241. doi:10.1111/j.1432-2277.2008.00770.x
Li Z, Nickkholgh A, Yi X, Bruns H, Gross ML, Hoffmann K, Mohr E, Zorn M, Büchler MW, Schemmer P (2009) Melatonin protects kidney grafts from ischemia/reperfusion injury through inhibition of NF-kB and apoptosis after experimental kidney transplantation. J Pineal Res 46(4):365–372. doi:10.1111/j.1600-079X.2009.00672.x
Cekauskas A, Bruns H, Manikas M, Herr I, Gross ML, Zorn M, Jankevicius F, Strupas K, Schemmer P (2013) Sulforaphane decreases kidney injury after transplantation in rats: role of mitochondrial damage. Ann Transplant 18:488–496. doi:10.12659/AOT.884013
Minor T, Paul A (2013) Hypothermic reconditioning in organ transplantation. Curr Opin Organ Transplant 18(2):161–167. doi:10.1097/MOT.0b013e32835e29de
Minor T, Koetting M, Kaiser G, Efferz P, Luer B, Paul A (2011) Hypothermic reconditioning by gaseous oxygen improves survival after liver transplantation in the pig. Am J Transplant 11(12):2627–2634. doi:10.1111/j.1600-6143.2011.03731.x
Minor T, Stegemann J, Hirner A, Koetting M (2009) Impaired autophagic clearance after cold preservation of fatty livers correlates with tissue necrosis upon reperfusion and is reversed by hypothermic reconditioning. Liver Transpl 15(7):798–805. doi:10.1002/lt.21751
Tolba RH, Akbar S, Puetz U, Minor T (2000) Use and limitations of reconditioning ischemically damaged livers from non-heart-beating donors by venous oxygen persufflation. Transplant Proc 32(7):2118–2119
Yagi S, Nagai K, Kadaba P, Afify M, Teramukai S, Uemoto S, Tolba RH (2013) A novel organ preservation for small partial liver transplantations in rats: venous systemic oxygen persufflation with nitric oxide gas. Am J Transplant 13(1):222–228. doi:10.1111/j.1600-6143.2012.04310.x
Gallinat A, Paul A, Efferz P, Luer B, Kaiser G, Wohlschlaeger J, Treckmann J, Minor T (2012) Hypothermic reconditioning of porcine kidney grafts by short-term preimplantation machine perfusion. Transplantation 93(8):787–793. doi:10.1097/TP.0b013e3182492201
Koetting M, Frotscher C, Minor T (2010) Hypothermic reconditioning after cold storage improves postischemic graft function in isolated porcine kidneys. Transpl Int 23(5):538–542. doi:10.1111/j.1432-2277.2009.01014.x
Sato E, Hachisuka T, Yokoyama I, Ohbayashi M, Asai J, Takagi H (1995) Effectiveness of Carolina rinse solution after cold ischemic storage of rat livers: biochemical and histological analysis using perfusion model. Eur Surg Res 27(1):49–56
Authorship roles
HB and PS wrote the paper
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Bruns, H., Schemmer, P. Machine perfusion in solid organ transplantation: where is the benefit?. Langenbecks Arch Surg 399, 421–427 (2014). https://doi.org/10.1007/s00423-014-1161-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00423-014-1161-2