Research Papers

Rewarming Machine Perfusion System for Liver Transplantation

[+] Author and Article Information
Hiromichi Obara

Department of Mechanical Engineering,
Tokyo Metropolitan University,
1-1 Minamiosawa, Hachioji,
Tokyo, Japan
e-mail: obara@tmu.ac.jp

Naoto Matsuno

Department of Transplantation,
Division for Advanced Medical Sciences,
Clinical Research Center,
National Center for Child Health and Development,
2-10-1 Okura Setagaya-ku,
Tokyo, Japan

Takanobu Shigeta

Department of Transplantation,
Clinical Research Center,
National Center for Child Health
and Development,
2-10-1 Okura Setagaya-ku,
Tokyo, Japan
Division of Hepato-Biliary-Pancreatic
and Transplant Surgery,
Kyoto University,
Kyoto, Japan

Shin Enosawa

Division for Advanced Medical Sciences,
Clinical Research Center,
National Center for Child Health and Development,
2-10-1 Okura Setagaya-ku,
Tokyo, Japan

Toshihiko Hirano

Department of Clinical Pharmacology,
Tokyo University of Pharmacy and Life Science,
1432-1 Horinouchi, Hachioji,
Tokyo, Japan

Hiroshi Mizunuma

Department of Mechanical Engineering,
Tokyo Metropolitan University,
1-1 Minamiosawa, Hachioji,
Tokyo, Japan

1Corresponding author.

Manuscript received December 24, 2012; final manuscript received June 17, 2013; published online October 25, 2013. Assoc. Editor: Keefe B. Manning.

J. Med. Devices 7(4), 041011 (Oct 25, 2013) (7 pages) Paper No: MED-12-1161; doi: 10.1115/1.4025189 History: Received December 24, 2012; Revised June 17, 2013

The liver is one of the most essential organs, and transplantation is an established treatment for patients with end-stage disease who have lost their liver function. However, organ shortage is a critical problem in transplantation; thus, the development of an innovative preservation system to adopt critical grafts obtained from extended criteria donors or donation after cardiac death donors as viable organs for transplantation is necessary. We recently developed a novel rewarming machine perfusion preservation system for liver transplantation, and herein discuss this system, which allows the perfusion temperature to be controlled during the transition from hypothermic to subnormothermic conditions. This system has two functions: (1) the preservation and recovery of organ function and (2) screening the organ for viability. To achieve these functions, this system has three features: (1) temperature control of the preservation perfusate and liver graft, (2) dual-controlled perfusion of the portal vein and hepatic artery, and (3) real-time monitoring of the perfusion conditions, including the flow rate, perfusion pressure and temperature. This system was useful for liver preservation and for evaluating the graft viability and recovery of functions during machine perfusion before transplantation. This novel rewarming machine preservation system was tested in an experimental model using porcine liver grafts. We report that this system has certain advantages in liver preservation, and believe that this system will positively contribute to the expansion of the organ donor pool.

Copyright © 2013 by ASME
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Talbot, D., and D'Alessandro, A. M., 2009, Organ Donation and Transplantation After Cardiac Death, Oxford University, New York, Chap. 13.
Ciria, R., Briceno, J., Rufian, S., Luque, A., and Lopez-Cillero, P., 2012, “Donation After Cardiac Death: Where, When, and How?” Transplant. Proc., 44(6), pp. 1470–1474. [CrossRef] [PubMed]
Monbaliu, D., Pirenne, J., and Talbot, D., 2012, “Liver Transplantation Using Donation After Cardiac Death Donors,” J. Hepatol., 56(2), pp. 474–485. [CrossRef] [PubMed]
St. Peter, S. D., Imber, C. J., and Friend, P. J., 2002, “Liver and Kidney Preservation by Perfusion,” Lancet, 359(9306), pp. 604–613. [CrossRef] [PubMed]
Dutkowski, P., de Rougemont, O., and Clavien, P., 2008, “Machine Perfusion for ‘Marginal’ Liver Grafts,” Am. J. Transplant., 8(5), pp. 917–924. [CrossRef] [PubMed]
Vekemans, K., Liu, Q., Pirenne, J., and Monbaliu, D., 2008, “Artificial Circulation of the Liver: Machine Perfusion as a Preservation Method in Liver Transplantation,” Anat. Rec., 291(6), pp. 735–740. [CrossRef]
Yuan, X., Theruvath, A. J., Ge, X., Floerchinger, B., Jurisch, A., García-Cardeña, G., and Tullius, S. G., 2010, “Machine Perfusion or Cold Storage in Organ Transplantation: Indication, Mechanisms, and Future Perspectives,” Transpl. Int., 23(6), pp. 561–570. [CrossRef] [PubMed]
Moers, C., Smits, J. M., Maathuis, M.-H. J., Treckmann, J., van Gelder, F., Napieralski, B. P., van Kasterop-Kutz, M., van der Heide, J. J. H., Squifflet, J.-P., van Heurn, E., Kirste, G. R., Rahmel, A., Leuvenink, H. G. D., Paul, A., Pirenne, J., and Ploeg, R. J., 2009, “Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation,” N. Engl. J. Med., 360, pp. 7–19. [CrossRef] [PubMed]
Moers, C., Pirenne, J., Paul, A., and Ploeg, R. J., 2012, “Machine Perfusion or Cold Storage in Deceased-Donor Kidney Transplantation,” N. Engl. J. Med., 366(8), pp. 770–771. [CrossRef] [PubMed]
Pienaar, B. H., Lindell, S. L., Van Gulik, T., Southard, J. H., and Belzer, F. O., 1990, “Seventy-Two-Hour Preservation of the Canine Liver by Machine Perfusion,” Transplantation, 49, 258–260. [CrossRef] [PubMed]
Kozaki, K., Uchiyama, M., Nemoto, T., Degawa, H., Takeuchi, H., Matsuno, N., Sakurai, E., Kozaki, M., and Nagao, T., 1997, “Usefulness of a Combination of Machine Perfusion and Pentoxifylline for Porcine Liver Transplantation From Non-Heart-Beating Donors With Prolonged Hypotension,” Transplant. Proc., 29(8), pp. 3476–3477. [CrossRef] [PubMed]
Guarrera, J. V., Estevez, J., BoykinJ., Boyce, R., Rashid, J., Sun, S., and Arrington, B., 2005, “Hypothermic Machine Perfusion of Liver Grafts for Transplantation: Technical Development in Human Discard and Miniature Swine Models,” Transplant. Proc., 37(1), pp. 323–325. [CrossRef] [PubMed]
Plaats, A.′T., Hart, N. A., Verkerke, G. J., Leuvenink, H. G. D., Ploeg, R. J., and Rakhorst, G., 2004, “Hypothermic Machine Preservation in Liver Transplantation Revisited: Concepts and Criteria in the New Millennium,” Ann. Biomed. Eng., 32(4), pp. 623–631. [CrossRef] [PubMed]
Plaats, A., and Maathuis, M., 2006, “The Groningen Hypothermic Liver Perfusion Pump: Functional Evaluation of a New Machine Perfusion System,” Ann. Biomed. Eng., 34(12), pp. 1924–1934. [CrossRef] [PubMed]
Monbaliu, D., Vekemans, K., De Vos, R., Brassil, J., Heedfeld, J., Qiang, L., D'hollander, M., Roskams, T., and Pirenne, J., 2007, “Hemodynamic, Biochemical, and Morphological Characteristics During Preservation of Normal Porcine Livers by Hypothermic Machine Perfusion,” Transplant. Proc., 39(8), pp. 2652–2658. [CrossRef] [PubMed]
Dutkowski, P., Furrer, K., Tian, Y., Graf, R., and Clavien, P.-A., 2006, “Novel Short-Term Hypothermic Oxygenated Perfusion (HOPE) System Prevents Injury in Rat Liver Graft From Non-Heart Beating Donor,” Ann. Surg., 244(6), pp. 968–977. [CrossRef] [PubMed]
Shigeta, T., Matsuno, N., Huai-Che, H., Obara, H., Mizunuma, H., Hirano, T., Uemoto, S., and Enosawa, S., 2012, “A Basic Consideration for Porcine Liver Preservation Using a Novel Continuous Machine Perfusion Device,” Transplant. Proc., 44(4), pp. 942–945. [CrossRef] [PubMed]
Guarrera, J. V., Henry, S. D., Samstein, B., Odeh-Ramadan, R., Kinkhabwala, M., Goldstein, M. J., Ratner, L. E., Renz, J. F., Lee, H. T., Brown, R. S., and Emond, J. C., 2010, “Hypothermic Machine Preservation in Human Liver Transplantation: The First Clinical Series,” Am. J. Transplant., 10(2), pp. 372–381. [CrossRef] [PubMed]
Naruse, K., Sakai, Y., GuoL., Natori, T., Shindoh, T., Karasawa, Y., Iida, Y., Kojima, K., Michishita, K., and Makuuchi, M., 2003, “Development of a New Extracorporeal Whole-Liver Perfusion System,” Int. J. Artif. Organs, 6(3), pp. 211–217. [CrossRef]
Tolboom, H., Pouw, R., Uygun, K., Tanimura, Y., Izamis, M.-L., Berthiaume, F., and Yarmush, M. L., 2007, “A Model for Normothermic Preservation of the Rat Liver,” Tissue Eng., 13(8), pp. 2143–2151. [CrossRef] [PubMed]
Fondevila, C., Hessheimer, A. J., Maathuis, M.-H. J., Muñoz, J., Taurá, P., Calatayud, D., Leuvenink, H., Rimola, A., Ploeg, R. J., and García-Valdecasas, J. C., 2011, “Superior Preservation of DCD Livers With Continuous Normothermic Perfusion,” Ann. Surg., 254(6), pp. 1000–1007. [CrossRef] [PubMed]
Tolboom, H., IzamisM.-L., Sharma, N., Milwid, J. M., Sc, M., Uygun, K., and Yarmush, M. L., 2011, “Subnormothermic Machine Perfusion at Both 20 °C and 30 °C Recovers Ischemic Rat Livers for Successful Transplantation,” J. Surg. Res., 8, pp. 1–8. [CrossRef]
Olschewski, P., Gass, P., Ariyakhagorn, V., Jasse, K., Hunold, G., Menzel, M., Schoning, W., Schmitz, V., Neuhaus, P., and Puhl, G., 2010, “The Influence of Storage Temperature During Machine Perfusion on Preservation Quality of Marginal Donor Livers,” Cryobiology, 60(3), pp. 337–343. [CrossRef] [PubMed]
Vairetti, M., Ferrigno, A., Rizzo, V., Boncompagni, E., Carraro, A., Gringeri, E., Milanesi, G., Barni, S., Freitas, I., and Cillo, U., 2008, “Correlation Between the Liver Temperature Employed During Machine Perfusion and Reperfusion Damage: Role of Ca2+,” Liver Transpl. Surg., 14(4), pp. 494–503. [CrossRef]
Vairetti, M., Ferrigno, A., Carlucci, F., Tabucchi, A., Rizzo, V., Boncompagni, E., Neri, D., Gringeri, E., Freitas, I., and Cillo, U., 2009, “Subnormothermic Machine Perfusion Protects Steatotic Livers Against Preservation Injury: A Potential for Donor Pool Increase?” Liver Transpl. Surg., 15(1), pp. 20–29. [CrossRef]
Lüer, B., Koetting, M., Efferz, P., and Minor, T., 2010, “Role of Oxygen During Hypothermic Machine Perfusion Preservation of the Liver,” Transplant Int., 23(9), pp. 944–950. [CrossRef]
Nishida, S., Nakamura, N., Kadono, J., Komokata, T., Sakata, R., Madariaga, J. R., and Tzakis, A. G., 2006, “Intrahepatic Biliary Strictures After Liver Transplantation,” J. Hepato-Biliary-Pancreatic Surg., 13(6), pp. 511–516. [CrossRef]
Obara, H., Matsuno, N., Enosawa, S., Shigeta, T., Huai-Che, H., Hirano, T., Muto, M., Kasahara, M., Uemoto, S., and Mizunuma, H., 2012, “Pretransplant Screening and Evaluation of Liver Graft Viability Using Machine Perfusion Preservation in Porcine Transplantation,” Transplant. Proc., 44(4), pp. 959–961. [CrossRef] [PubMed]
Matsuno, N., Sakurai, E., Tamaki, I., Furuhashi, K., Saito, A., Zhang, S., Kozaki, K., Shimada, A., Miyamoto, K., and Kozaki, M., 1994, “Effectiveness of Machine Perfusion Preservation as a Viability Determination Method for Kidneys Procured From Non-Heart-Beating Donors,” Transplant. Proc.26, pp. 2421–2422. [PubMed]
Matsuno, N., Konno, O., Mejit, A., Jyojima, Y., Akashi, I., Nakamura, Y., Iwamoto, H., Hama, K., Iwahori, T., Ashizawa, T., and Nagao, T., 2006, “Application of Machine Perfusion Preservation as a Viability Test for Marginal Kidney Graft,” Transplantation, 82(11), pp. 1425–1428. [CrossRef] [PubMed]
Nyberg, S. L., Baskin-Bey, E. S., Kremers, W., Prieto, M., Henry, M. L., and Stegall, M. D., 2009, “Improving the Prediction of Donor Kidney Quality: Deceased Donor Score and Resistive Indices,” Transplantation, 80, pp. 925–929. [CrossRef]
Shigeta, T., Matsuno, N., Obara, H., Mizunuma, H., Kanazawa, H., Tanaka, H., Fukuda, A., Sakamoto, S., Kasahara, M., Uemoto, S., and Enosawa, S., 2012, “Functional Recovery of Donation After Cardiac Death Liver Graft by Continuous Machine Perfusion Preservation in Pigs,” Transplant. Proc., 44(4), pp. 946–947. [CrossRef] [PubMed]
Devlin, J., Dunne, J. B., Sherwood, R. A., Chambers, S. M., Tan, K. C., Peters, T. J., and Williams, R., 1995, “Relationship Between Early Liver Graft Viability and Enzyme Activities in Effluent Preservation Solution,” Transplantation, 60, pp. 627–631. [CrossRef] [PubMed]
Lange, R., Erhard, J., Rauen, U., de Groot, H., and Eigler, F. W., 1996, “Determination of Hepatocellular Enzymes in Effluent of Human Liver Grafts for Preoperative Evaluation of Transplant Quality,” Transplantation, 62, pp. 1255–1259. [CrossRef] [PubMed]


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Fig. 1

A schematic diagram of the machine perfusion system

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Fig. 2

The transplantation procedure from procurement to implantation

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Fig. 3

The temperature control charts of the HMP (a) and RMP (b) conditions (Tx: transplantation, RP: reperfusion)

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Fig. 4

The average temperature transition of the preservation perfusate and liver graft during a period of 90–120 min of the RMP experiment (n = 3)

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Fig. 5

The PV and the HA pressure during machine perfusion

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Fig. 6

The average HA pressure transitions during HMP and RMP

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Fig. 7

The cumulative release of (a) AST, (b) ALT and (c) LDH during machine perfusion (empty symbols indicate HMP and solid symbols indicate RMP)

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Fig. 8

The enzyme release rate of RMP compared with that of HMP (striped bars indicate HMP and solid bars indicate RMP)



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