Metabolomic Analysis, Perfusate Composition, and Pseudo-physiology of the Isolated Liver During Ex Situ Normothermic Machine Perfusion

Hessheimer, Amelia J.; Vengohechea, Jordi; Fondevila, Constantino

doi:10.1097/tp.0000000000004530

Cited by 4 publications

(4 citation statements)

References 10 publications

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“…However, the identified key BA in IRI pave the way for a rapid translational application. Third, it is important to acknowledge that BA physiology also involves the gut-liver axis which is not included in our isolated ex-situ reperfusion model 50 . This does however not preclude from analyzing bile composition and provide valuable insights as it takes into account both BA uptake and formation by the hepatocyte and the cholangiocyte 11 , 13 .…”

Section: Discussionmentioning

confidence: 99%

Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury

Rossignol,

Muller,

Brunet

et al. 2024

Sci Rep

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Bile acids (BA) are key for liver regeneration and injury. This study aims at analyzing the changes in the BA pool induced by ischemia-reperfusion (IRI) and investigates the impact of hypothermic oxygenated perfusion (HOPE) on the BA pool compared to static cold storage (SCS). In a porcine model of IRI, liver grafts underwent 30 min of asystolic warm ischemia followed by 6 h of SCS (n = 6) ± 2 h of HOPE (n = 6) and 2 h of ex-situ warm reperfusion. The BA pool in bile samples was analyzed with liquid chromatography coupled with tandem mass spectrometry. We identified 16 BA and observed significant changes in response to ischemia-reperfusion, which were associated with both protective and injury mechanisms. Second, HOPE-treated liver grafts exhibited a more protective BA phenotype, characterized by a more hydrophilic BA pool compared to SCS. Key BA, such as GlycoCholic Acid, were identified and were associated with a decreased transaminase release and improved lactate clearance during reperfusion. Partial Least Square-Discriminant Analysis revealed a distinct injury profile for the HOPE group. In conclusion, the BA pool changes with liver graft IRI, and preservation with HOPE results in a protective BA phenotype compared to SCS.

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Section: Discussionmentioning

confidence: 99%

Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury

Rossignol,

Muller,

Brunet

et al. 2024

Sci Rep

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show abstract

“…Organ failure may be secondary to a missing key metabolic component required for maintenance energy homoeostasis or a deterioration in perfusate quality over time as blood products were not topped up or refreshed 17 . This model also remains non-physiological without a gut-liver axis or automated circadian variation 18 . These reasons may explain why most livers inevitably began failing after 5–7 days of perfusion.…”

Section: Discussionmentioning

confidence: 99%

Long-term ex situ normothermic perfusion of human split livers for more than 1 week

Lau

Dennis

et al. 2023

Nat Commun

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Current machine perfusion technology permits livers to be preserved ex situ for short periods to assess viability prior to transplant. Long-term normothermic perfusion of livers is an emerging field with tremendous potential for the assessment, recovery, and modification of organs. In this study, we aimed to develop a long-term model of ex situ perfusion including a surgical split and simultaneous perfusion of both partial organs. Human livers declined for transplantation were perfused using a red blood cell-based perfusate under normothermic conditions (36 °C) and then split and simultaneously perfused on separate machines. Ten human livers were split, resulting in 20 partial livers. The median ex situ viability was 125 h, and the median ex situ survival was 165 h. Long-term survival was demonstrated by lactate clearance, bile production, Factor-V production, and storage of adenosine triphosphate. Here, we report the long-term ex situ perfusion of human livers and demonstrate the ability to split and perfuse these organs using a standardised protocol.

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“…Such underlying mechanisms are largely unknown under physiological conditions in the main cardio-vasculature and even more with injury, such as hypoxia and IRI in specific organs. We may well expect such protective ECs features to change rapidly when machine perfusion technology is applied to organs ex situ, lacking communication with the entire body, and moreover, when “treating” isolated organs with various unphysiological perfusates with more or fewer additives and at all temperatures [ 16 , 17 ].…”

Section: Mitochondria and Endothelial Cells Under Physiological Condi...mentioning

confidence: 99%

Endothelial Cells and Mitochondria: Two Key Players in Liver Transplantation

Parente

Carvalho

Schlegel

2023

IJMS

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Building the inner layer of our blood vessels, the endothelium forms an important line communicating with deeper parenchymal cells in our organs. Previously considered passive, endothelial cells are increasingly recognized as key players in intercellular crosstalk, vascular homeostasis, and blood fluidity. Comparable to other cells, their metabolic function strongly depends on mitochondrial health, and the response to flow changes observed in endothelial cells is linked to their mitochondrial metabolism. Despite the direct impact of new dynamic preservation concepts in organ transplantation, the impact of different perfusion conditions on sinusoidal endothelial cells is not yet explored well enough. This article therefore describes the key role of liver sinusoidal endothelial cells (LSECs) together with their mitochondrial function in the context of liver transplantation. The currently available ex situ machine perfusion strategies are described with their effect on LSEC health. Specific perfusion conditions, including perfusion pressure, duration, and perfusate oxygenation are critically discussed considering the metabolic function and integrity of liver endothelial cells and their mitochondria.

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Metabolomic Analysis, Perfusate Composition, and Pseudo-physiology of the Isolated Liver During Ex Situ Normothermic Machine Perfusion

Cited by 4 publications

References 10 publications

Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury

Comprehensive bile acid pool analysis during ex-vivo liver perfusion in a porcine model of ischemia-reperfusion injury

Long-term ex situ normothermic perfusion of human split livers for more than 1 week

Endothelial Cells and Mitochondria: Two Key Players in Liver Transplantation

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