Current status and future of subnormothermic machine perfusion preservation

Recently, it has become clear that machine perfusion preservation is a more beneficial than cold storage. Cold-induced preservation injury causes inadequate cellular metabolic function, the depletion of energy stores or the deleterious direct effects of cooling. Normothermic machine perfusion (NMP)...

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Published inOrgan Biology Vol. 29; no. 1; pp. 13 - 20
Main Authors Takahashi, Hiroyuki, Ishii, Daisuke, Toriumi, Asuka, Matsuno, Naoto, Yokoo, Hideki, Iwata, Hiroyoshi, Teraguchi, Hiroyuki, Otani, Masahide, Imai, KoJi, Hagiwara, Masahiro, Obara, Hiromichi
Format Journal Article
LanguageJapanese
Published The Japan Society for Organ Preservation and Biology 2022
一般社団法人 日本臓器保存生物医学会
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ISSN1340-5152
2188-0204
DOI10.11378/organbio.29.13

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Abstract Recently, it has become clear that machine perfusion preservation is a more beneficial than cold storage. Cold-induced preservation injury causes inadequate cellular metabolic function, the depletion of energy stores or the deleterious direct effects of cooling. Normothermic machine perfusion (NMP) can help maintain and recover graft function, and evaluate the viability. However, because it requires high level of oxygen, blood-based perfusates those may increase the risk of microvascular failure and bacterial growth, are used. Therefore, NMP remains a challenging problem. On the other hand, subnormothermic machine perfusion (SNMP) at around 20℃-25℃ needs lower level of oxygen compared to NMP. Herein, we demonstrate the current status and future of SNMP.
AbstractList Recently, it has become clear that machine perfusion preservation is a more beneficial than cold storage. Cold-induced preservation injury causes inadequate cellular metabolic function, the depletion of energy stores or the deleterious direct effects of cooling. Normothermic machine perfusion (NMP) can help maintain and recover graft function, and evaluate the viability. However, because it requires high level of oxygen, blood-based perfusates those may increase the risk of microvascular failure and bacterial growth, are used. Therefore, NMP remains a challenging problem. On the other hand, subnormothermic machine perfusion (SNMP) at around 20℃-25℃ needs lower level of oxygen compared to NMP. Herein, we demonstrate the current status and future of SNMP.
Recently, it has become clear that machine perfusion preservation is a more beneficial than cold storage. Cold-induced preservation injury causes inadequate cellular metabolic function, the depletion of energy stores or the deleterious direct effects of cooling. Normothermic machine perfusion (NMP) can help maintain and recover graft function, and evaluate the viability. However, because it requires high level of oxygen, blood-based perfusates those may increase the risk of microvascular failure and bacterial growth, are used. Therefore, NMP remains a challenging problem. On the other hand, subnormothermic machine perfusion (SNMP) at around 20℃-25℃ needs lower level of oxygen compared to NMP. Herein, we demonstrate the current status and future of SNMP. 近年, 機械灌流保存が冷却保存よりも有益であることが明らかになってきた. 冷温によって引き起こされる保存傷害は, 不十分な細胞代謝機能やエネルギー貯蔵の枯渇, 冷却による直接的な有害効果を引き起こす. 常温機械灌流法(NMP)は, 移植片機能の維持と回復, および生存率の評価に役立つ. しかし, 高レベルの酸素を必要とするため, 微小血管障害や細菌増殖のリスクを高める可能性のある血液製剤が使用される. それゆえ, 常温機械灌流法は依然として困難な問題である. 一方, 20°C-25°C付近の室温機械灌流法(SNMP)は, NMPに比べて必要な酸素レベルが低くなる. ここでは, SNMPの現状と将来について説明する.
Author Ishii, Daisuke
Toriumi, Asuka
Imai, KoJi
Teraguchi, Hiroyuki
Yokoo, Hideki
Obara, Hiromichi
Takahashi, Hiroyuki
Hagiwara, Masahiro
Matsuno, Naoto
Otani, Masahide
Iwata, Hiroyoshi
Author_FL 大谷 将秀
石井 大介
松野 直徒
寺口 博也
今井 浩二
Obara Hiromichi
岩田 浩義
鳥海 飛鳥
髙橋 裕之
萩原 正弘
横尾 英樹
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  organization: Department of Mechanical System Engineering, Tokyo Metropolitan University
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References 4) Reddy S, Greenwood J, Maniakin N, Bhattacharjya S, Zilvetti M, Brockmann J, et al. Non-heart-beating donor porcine livers: the adverse effect of cooling. Liver Transpl. 2005 Jan; 11 (1): 35-8.
3) de Rougemont O, Breitenstein S, Leskosek B, Weber A, Graf R, Clavien PA, et al. One hour hypothermic oxygenated perfusion (HOPE) protects nonviable liver allografts donated after cardiac death. Ann Surg. 2009 May; 8 (5): 674-84.
20) Shonaka T, Matsuno N, Obara H, Yoshikawa R, Nishikawa Y, Ishihara Y, et al Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model. PLoS One. 2019 Dec; 14 (12): e0226183.
7) Kato A, Singh S, McLeish KR, Edwards MJ, Lentsch AB. Mechanisms of hypothermic protection against ischemic liver injury in mice. Am J Physiol Gastrointest Liver Physiol. 2002 Apr; 282 (4): G608-16.
15) Watanabe R, Kimura M, Matsuno N, Shigeta T, Hsu HC, Muto M, et al. Significant effect of initial flush out solution with use of CPD for DCD liver transplantation. Low Temperature Medicine. 2012; 38 (2): 47.
16) Hsu HC, Matsuno N, Machida N, Enosawa S. Improved Recovery of Hepatocytes Isolated From Warm Ischemic Rat Liver by Citrate Phosphate Dextrose (CPD)-Supplemented Euro-Collins solution. Cell Med. 2013 May; 5 (2-3): 97-101.
6) Vairetti M, Ferrigno A, Carlucci F, Tabucchi A, Rizzo V, Boncompagni E, et al. Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase? Liver Transpl. 2009 Jan; 15 (1): 20-9.
11) Ferrigno A, Rizzo V, Boncompagni E, Bianchi A, Gringeri E, Neri D, et al. Machine perfusion at 20°C reduces preservation damage to livers from non-heart beating donors. Cryobiology. 2011 Apr; 62 (2); 152-8.
17) Sakai H. Overview of Potential Clinical Applications of Hemoglobin Vesicles (HbV) as Artificial Red Cells, Evidenced by Preclinical Studies of the Academic Research Consortium. J Funct Biomater. 2017 Mar; 8 (1):10.
1) Moers C, Smits JM, Maathuis MH, Treckmann J, van Gelder F, Napieralski BP, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009 Jan 1;360 (1): 7-19.
14) Kakizaki Y, Miyagi S, Shimizu K, Miyazawa K, Nakanishi W, Tokodai K, et al. The Effects of Short-term Subnormothermic Perfusion After Cold Preservation on Liver Grafts From Donors After Circulatory Death: An Ex Vivo Rat Model. Transplantation. 2018 Apr; 102 (4): e147-e154.
27) Hoyer DP, Mathé Z, Gallinat A, Canbay AC, Treckmann JW, Rauen U, et al. Controlled Oxygenated Rewarming of Cold Stored Livers Prior to Transplantation: First Clinical Application of a New Concept. Transplantation. 2016 Jan; 100 (1): 147-52.
5) Olschewski P, Gass P, Ariyakhagorn V, Jasse K, Hunold G, Menzel M, et al. The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers. Cryobiology. 2010 Jun; 60 (3): 347-43.
23) Westerkamp AC, Mahboub P, Meyer SL, Hottenrott M, Ottens PJ, Wiersema-Buist J, et al. End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature. Liver Transpl. 2015 Oct; 21 (10): 1300-11.
18) Sakai H, Sou K, Tsuchida E. Hemoglobin-vesicles as an artificial oxygen carrier. Methods Enzymol. 2009; 465: 363-84.
10) Berardo C, Di Pasqua LG, Siciliano V, Rizzo V, Richelmi P, Ferrigno A, et al. Machine Perfusion at 20°C Prevents Ischemic Injury and Reduces Hypoxia-Inducible Factor-1α Expression During Rat Liver Preservation. Ann Transplant. 2017 Sep; 22: 581-589.
12) Fontes P, Lopez R, van der Plaats A, Vodovotz Y, Minervini M, Scott V, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions. Am J Transplanta. 2015 Feb; 15 (2): 381-94.
19) Shonaka T, Matsuno N, Obara H, Yoshikawa R, Nishikawa Y, Gouchi M, et al. Application of Perfusate With Human-Derived Oxygen Carrier Solution Under Subnormothermic Machine Perfusion for Donation After Cardiac Death Liver Grafts in Pigs. Transplant Proc. 2018 Nov; 50 (9): 2821-2825.
21) Iwata H, Toriumi A, Ishii D, Yamamoto A, Sato Y, Takahashi H, et al. Applicability of Hemoglobin Vesicles as Transplantable Liver Perfusion Preservation Solution. Artificial Blood. 2021 Sep; 29 (1): 43-49.
22) Spetzler VN, Goldaracena N, Echiverri J, Kaths JM, Louis KS, Adeyi OA, et al. Subnormothermic ex vivo liver perfusion is a safe alternative to cold static storage for preserving standard criteria grafts. Liver Transpl. 2016 Nov; 22 (1): 111-9.
25) Shigeta T, Matsuno N, Obara H, Kanazawa H, Tanaka H, Fukuda A, et al. Impact of rewarming preservation by continuous machine perfusion: improved post-transplant recovery in pigs. Transplant Proc. 2013 Jun; 45 (5): 1684-9.
26) Minor T, Efferz P, Fox M, Wohlschlaeger J, Lüer B. Controlled oxygenated rewarming of cold stored liver grafts by thermally graduated machine perfusion prior to reperfusion. Am J Transplant. 2013 Jun; 13 (6): 1450-60.
13) Kakizaki Y, Miyagi S, Shimizu K, Kumata H, Matsumura M, Miyazaki Y, et al. Effects of Subnormothermic Perfusion Before Transplantation for Liver Grafts from Donation After Cardiac Death: A Simplified Dripping Perfusion Methods in Pigs. Transplant Proc. 2018 Jun; 50 (5): 1538-1543.
8) Bruinsma BG, Yeh H, Ozer S, Martins PN, Farmer A, Wu W, et al. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation. Am J Transplant. 2014 Jun; 14 (6): 1400-9.
9) Tolboom H, Izamis ML, Sharma N, Milwid JM, Uygun B, Berthiaume F, et al. Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation. J Surg Res. 2012 Jun; 175 (1): 149-56.
24) Obara H, Matsuno N, Shigeta T, Enosawa S, Hirano T, Mizunuma H. Rewarming Machine Perfusion System for Liver Transplantation. J Med Devices. 2013 Dec; 7 (4): 041011-7.
2) Guarrera JV, Henry SD, Samstein B, Odeh-Ramadan R, Kinkhabwala M, Goldstein MJ, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant. 2010 Feb; 10 (2): 372-81.
References_xml – reference: 6) Vairetti M, Ferrigno A, Carlucci F, Tabucchi A, Rizzo V, Boncompagni E, et al. Subnormothermic machine perfusion protects steatotic livers against preservation injury: a potential for donor pool increase? Liver Transpl. 2009 Jan; 15 (1): 20-9.
– reference: 8) Bruinsma BG, Yeh H, Ozer S, Martins PN, Farmer A, Wu W, et al. Subnormothermic machine perfusion for ex vivo preservation and recovery of the human liver for transplantation. Am J Transplant. 2014 Jun; 14 (6): 1400-9.
– reference: 4) Reddy S, Greenwood J, Maniakin N, Bhattacharjya S, Zilvetti M, Brockmann J, et al. Non-heart-beating donor porcine livers: the adverse effect of cooling. Liver Transpl. 2005 Jan; 11 (1): 35-8.
– reference: 24) Obara H, Matsuno N, Shigeta T, Enosawa S, Hirano T, Mizunuma H. Rewarming Machine Perfusion System for Liver Transplantation. J Med Devices. 2013 Dec; 7 (4): 041011-7.
– reference: 5) Olschewski P, Gass P, Ariyakhagorn V, Jasse K, Hunold G, Menzel M, et al. The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers. Cryobiology. 2010 Jun; 60 (3): 347-43.
– reference: 23) Westerkamp AC, Mahboub P, Meyer SL, Hottenrott M, Ottens PJ, Wiersema-Buist J, et al. End-ischemic machine perfusion reduces bile duct injury in donation after circulatory death rat donor livers independent of the machine perfusion temperature. Liver Transpl. 2015 Oct; 21 (10): 1300-11.
– reference: 16) Hsu HC, Matsuno N, Machida N, Enosawa S. Improved Recovery of Hepatocytes Isolated From Warm Ischemic Rat Liver by Citrate Phosphate Dextrose (CPD)-Supplemented Euro-Collins solution. Cell Med. 2013 May; 5 (2-3): 97-101.
– reference: 9) Tolboom H, Izamis ML, Sharma N, Milwid JM, Uygun B, Berthiaume F, et al. Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation. J Surg Res. 2012 Jun; 175 (1): 149-56.
– reference: 12) Fontes P, Lopez R, van der Plaats A, Vodovotz Y, Minervini M, Scott V, et al. Liver preservation with machine perfusion and a newly developed cell-free oxygen carrier solution under subnormothermic conditions. Am J Transplanta. 2015 Feb; 15 (2): 381-94.
– reference: 17) Sakai H. Overview of Potential Clinical Applications of Hemoglobin Vesicles (HbV) as Artificial Red Cells, Evidenced by Preclinical Studies of the Academic Research Consortium. J Funct Biomater. 2017 Mar; 8 (1):10.
– reference: 26) Minor T, Efferz P, Fox M, Wohlschlaeger J, Lüer B. Controlled oxygenated rewarming of cold stored liver grafts by thermally graduated machine perfusion prior to reperfusion. Am J Transplant. 2013 Jun; 13 (6): 1450-60.
– reference: 15) Watanabe R, Kimura M, Matsuno N, Shigeta T, Hsu HC, Muto M, et al. Significant effect of initial flush out solution with use of CPD for DCD liver transplantation. Low Temperature Medicine. 2012; 38 (2): 47.
– reference: 27) Hoyer DP, Mathé Z, Gallinat A, Canbay AC, Treckmann JW, Rauen U, et al. Controlled Oxygenated Rewarming of Cold Stored Livers Prior to Transplantation: First Clinical Application of a New Concept. Transplantation. 2016 Jan; 100 (1): 147-52.
– reference: 11) Ferrigno A, Rizzo V, Boncompagni E, Bianchi A, Gringeri E, Neri D, et al. Machine perfusion at 20°C reduces preservation damage to livers from non-heart beating donors. Cryobiology. 2011 Apr; 62 (2); 152-8.
– reference: 19) Shonaka T, Matsuno N, Obara H, Yoshikawa R, Nishikawa Y, Gouchi M, et al. Application of Perfusate With Human-Derived Oxygen Carrier Solution Under Subnormothermic Machine Perfusion for Donation After Cardiac Death Liver Grafts in Pigs. Transplant Proc. 2018 Nov; 50 (9): 2821-2825.
– reference: 7) Kato A, Singh S, McLeish KR, Edwards MJ, Lentsch AB. Mechanisms of hypothermic protection against ischemic liver injury in mice. Am J Physiol Gastrointest Liver Physiol. 2002 Apr; 282 (4): G608-16.
– reference: 13) Kakizaki Y, Miyagi S, Shimizu K, Kumata H, Matsumura M, Miyazaki Y, et al. Effects of Subnormothermic Perfusion Before Transplantation for Liver Grafts from Donation After Cardiac Death: A Simplified Dripping Perfusion Methods in Pigs. Transplant Proc. 2018 Jun; 50 (5): 1538-1543.
– reference: 20) Shonaka T, Matsuno N, Obara H, Yoshikawa R, Nishikawa Y, Ishihara Y, et al Impact of human-derived hemoglobin based oxygen vesicles as a machine perfusion solution for liver donation after cardiac death in a pig model. PLoS One. 2019 Dec; 14 (12): e0226183.
– reference: 3) de Rougemont O, Breitenstein S, Leskosek B, Weber A, Graf R, Clavien PA, et al. One hour hypothermic oxygenated perfusion (HOPE) protects nonviable liver allografts donated after cardiac death. Ann Surg. 2009 May; 8 (5): 674-84.
– reference: 14) Kakizaki Y, Miyagi S, Shimizu K, Miyazawa K, Nakanishi W, Tokodai K, et al. The Effects of Short-term Subnormothermic Perfusion After Cold Preservation on Liver Grafts From Donors After Circulatory Death: An Ex Vivo Rat Model. Transplantation. 2018 Apr; 102 (4): e147-e154.
– reference: 21) Iwata H, Toriumi A, Ishii D, Yamamoto A, Sato Y, Takahashi H, et al. Applicability of Hemoglobin Vesicles as Transplantable Liver Perfusion Preservation Solution. Artificial Blood. 2021 Sep; 29 (1): 43-49.
– reference: 2) Guarrera JV, Henry SD, Samstein B, Odeh-Ramadan R, Kinkhabwala M, Goldstein MJ, et al. Hypothermic machine preservation in human liver transplantation: the first clinical series. Am J Transplant. 2010 Feb; 10 (2): 372-81.
– reference: 10) Berardo C, Di Pasqua LG, Siciliano V, Rizzo V, Richelmi P, Ferrigno A, et al. Machine Perfusion at 20°C Prevents Ischemic Injury and Reduces Hypoxia-Inducible Factor-1α Expression During Rat Liver Preservation. Ann Transplant. 2017 Sep; 22: 581-589.
– reference: 22) Spetzler VN, Goldaracena N, Echiverri J, Kaths JM, Louis KS, Adeyi OA, et al. Subnormothermic ex vivo liver perfusion is a safe alternative to cold static storage for preserving standard criteria grafts. Liver Transpl. 2016 Nov; 22 (1): 111-9.
– reference: 1) Moers C, Smits JM, Maathuis MH, Treckmann J, van Gelder F, Napieralski BP, et al. Machine perfusion or cold storage in deceased-donor kidney transplantation. N Engl J Med. 2009 Jan 1;360 (1): 7-19.
– reference: 18) Sakai H, Sou K, Tsuchida E. Hemoglobin-vesicles as an artificial oxygen carrier. Methods Enzymol. 2009; 465: 363-84.
– reference: 25) Shigeta T, Matsuno N, Obara H, Kanazawa H, Tanaka H, Fukuda A, et al. Impact of rewarming preservation by continuous machine perfusion: improved post-transplant recovery in pigs. Transplant Proc. 2013 Jun; 45 (5): 1684-9.
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Snippet Recently, it has become clear that machine perfusion preservation is a more beneficial than cold storage. Cold-induced preservation injury causes inadequate...
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SubjectTerms extracorporeal membrane oxygenation
hemoglobin vesicles
liver
rewarming machine perfusion
subnormothermic machine perfusion
人工赤血球
体外式膜型人工肺
室温機械灌流法
復温機械灌流法
臓器保存法
Title Current status and future of subnormothermic machine perfusion preservation
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