Oxygenated Hypothermic Machine Perfusion After Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers

Westerkamp, Andrie C.; Karimian, Negin; Matton, A.; Mahboub, Paria; Rijn, Rianne van; Wiersema-Buist, Janneke; Boer, Marieke T. de; Leuvenink, Henri G. D.; Gouw, Annette S.H.; Lisman, Ton; Porte, Robert J.

doi:10.1097/tp.0000000000001081

Cited by 97 publications

(114 citation statements)

References 28 publications

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“…13 Furthermore, this study showed that high ATP levels upon reperfusion significantly correlated with decreased potassium. 13 Furthermore, this study showed that high ATP levels upon reperfusion significantly correlated with decreased potassium.…”

Section: Discussionmentioning

confidence: 63%

“…13 Only livers preserved in UW cold storage solution were included in the current study. Livers were selected from a previous study based on the type of preservation fluid used during organ procurement.…”

Section: Part A: Preclinical Studymentioning

confidence: 99%

“…[13][14][15] Prior to NMP, all livers were flushed with 1L cold NaCl 0.9% solution, followed by 500 mL warm NaCl 0.9% solution to flush out UW cold storage (control livers) or UW machine perfusion solution (DHOPE livers). [13][14][15] Prior to NMP, all livers were flushed with 1L cold NaCl 0.9% solution, followed by 500 mL warm NaCl 0.9% solution to flush out UW cold storage (control livers) or UW machine perfusion solution (DHOPE livers).…”

Section: Part A: Preclinical Studymentioning

confidence: 99%

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Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers

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Hessels

Rijn

et al. 2019

American Journal of Transplantation

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Liver transplantation is frequently associated with hyperkalemia, especially after graft reperfusion. Dual hypothermic oxygenated machine perfusion (DHOPE) reduces ischemia/reperfusion injury and improves graft function, compared to conventional static cold storage (SCS). We examined the effect of DHOPE on ex situ and in vivo shifts of potassium and sodium. Potassium and sodium shifts were derived from balance measurements in a preclinical study of livers that underwent DHOPE (n = 6) or SCS alone (n = 9), followed by ex situ normothermic reperfusion. Similar measurements were performed in a clinical study of DHOPE‐preserved livers (n = 10) and control livers that were transplanted after SCS only (n = 9). During DHOPE, preclinical and clinical livers released a mean of 17 ± 2 and 34 ± 6 mmol potassium and took up 25 ± 9 and 24 ± 14 mmol sodium, respectively. After subsequent normothermic reperfusion, DHOPE‐preserved livers took up a mean of 19 ± 3 mmol potassium, while controls released 8 ± 5 mmol potassium. During liver transplantation, blood potassium levels decreased upon reperfusion of DHOPE‐preserved livers while levels increased after reperfusion of SCS‐preserved liver, delta potassium levels were ‐0.77 ± 0.20 vs. +0.64 ± 0.37 mmol/L, respectively (P = .002). While hyperkalemia is generally anticipated during transplantation of SCS‐preserved livers, reperfusion of hypothermic machine perfused livers can lead to decreased blood potassium or even hypokalemia in the recipient.

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Section: Discussionmentioning

confidence: 63%

Section: Part A: Preclinical Studymentioning

confidence: 99%

Section: Part A: Preclinical Studymentioning

confidence: 99%

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Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers

Burlage

Hessels

Rijn

et al. 2019

American Journal of Transplantation

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“…So far, it remains obscure whether continuous perfusion, the avoidance of hypoxia or hypothermia, rewarming after storage, or all the abovementioned procedures are crucial for the effectiveness of machine preservation. 42-45 Both experimental models and clinical studies have used perfusate oxygenated under hypothermic 42,45 or normothermic conditions, 43,44 and it was found that using perfusate containing red blood cells led to attenuation, but not complete prevention, of biliary complications. 42,44 In view of these conflicting findings, further clinical studies are warranted to clarify the pathomechanism of early cholangiopathy after liver transplant.…”

Section: Discussionmentioning

confidence: 99%

Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine-Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled, Multicenter Study

Otto

Heise

Thies

et al. 2017

Transplantation Direct

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BackgroundArterial ex situ back-table perfusion (BP) reportedly reduces ischemic-type biliary lesion after liver transplantation. We aimed to verify these findings in a prospective investigation.MethodsOur prospective, randomized, controlled, multicenter study involved livers retrieved from patients in 2 German regions, and compared the outcomes of standard aortic perfusion to those of aortic perfusion combined with arterial ex situ BP. The primary endpoint was the incidence of ischemic-type biliary lesions over a follow-up of 2 years after liver transplantation, whereas secondary endpoints included 2-year graft survival, initial graft damage as reflected by transaminase levels, and functional biliary parameters at 6 months after transplantation.ResultsA total of 75 livers preserved via standard aortic perfusion and 75 preserved via standard aortic perfusion plus arterial BP were treated using a standardized protocol. The incidence of clinically apparent biliary lesions after liver transplantation (n = 9 for both groups; P = 0.947), the 2-year graft survival rate (standard aortic perfusion, 74%; standard aortic perfusion plus arterial BP, 68%; P = 0.34), and incidence of initial graft injury did not differ between the 2 perfusion modes. Although 33 of the 77 patients with cholangiography workups exhibited injured bile ducts, only 10 had clinical symptoms.ConclusionsContrary to previous findings, the present study indicated that additional ex situ BP did not prevent ischemic-type biliary lesions or ischemia-reperfusion injury after liver transplantation. Moreover, there was considerable discrepancy between cholangiography findings regarding bile duct changes and clinically apparent cholangiopathy after transplantation, which should be considered when assessing ischemic-type biliary lesions.

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“…Accordingly, some of the benefits of HMP are minimization of cold ischemia injury, improvement of grafts viability, and protection against biliary lesions [115, 116]. In the case of hypothermic oxygenated perfusion, it also provides the opportunity to restore mitochondrial redox activity and cellular energy status while the metabolism is still dampened by hypothermia [117].…”

Section: Classification Of Perfusion Techniques Based On Preservationmentioning

confidence: 99%

Organ Preservation into the 2020s: The Era of Dynamic Intervention

Petrenko

Carnevale

Somov

et al. 2019

Transfus Med Hemother

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Organ preservation has been of major importance ever since transplantation developed into a global clinical activity. The relatively simple procedures were developed on a basic comprehension of low-temperature biology as related to organs outside the body. In the past decade, there has been a significant increase in knowledge of the sequelae of effects in preserved organs, and how dynamic intervention by perfusion can be used to mitigate injury and improve the quality of the donated organs. The present review focuses on (1) new information about the cell and molecular events impacting on ischemia/reperfusion injury during organ preservation, (2) strategies which use varied compositions and additives in organ preservation solutions to deal with these, (3) clear definitions of the developing protocols for dynamic organ perfusion preservation, (4) information on how the choice of perfusion solutions can impact on desired attributes of dynamic organ perfusion, and (5) summary and future horizons.

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Oxygenated Hypothermic Machine Perfusion After Static Cold Storage Improves Hepatobiliary Function of Extended Criteria Donor Livers

Abstract: Two hours of oxygenated HMP after traditional SCS restores hepatic ATP levels and improves hepatobiliary function but does not reduce (preexisting) hepatobiliary injury in ECD livers.

Cited by 97 publications

References 28 publications

Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers

Opposite acute potassium and sodium shifts during transplantation of hypothermic machine perfused donor livers

Liver Preservation by Aortic Perfusion Alone Compared With Preservation by Aortic Perfusion and Additional Arterial Ex Situ Back-Table Perfusion With Histidine-Tryptophan-Ketoglutarate Solution: A Prospective, Randomized, Controlled, Multicenter Study

Organ Preservation into the 2020s: The Era of Dynamic Intervention

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