Observations and findings during the development of a subnormothermic/normothermic long-term ex vivo liver perfusion machine.

clearance free hemoglobin hemolysis lactate liver perfusion long-term perfusion perfusion parameters subnormothermic/normothermic perfusion

Journal

Artificial organs
ISSN: 1525-1594
Titre abrégé: Artif Organs
Pays: United States
ID NLM: 7802778

Informations de publication

Date de publication:
Feb 2023
Historique:
revised: 24 08 2022
received: 03 04 2022
accepted: 26 08 2022
pubmed: 16 9 2022
medline: 3 2 2023
entrez: 15 9 2022
Statut: ppublish

Résumé

Ex situliver machine perfusion at subnormothermic/normothermic temperature isincreasingly applied in the field of transplantation to store and evaluateorgans on the machine prior transplantation. Currently, various perfusionconcepts are in clinical and preclinical applications. Over the last 6 years ina multidisciplinary team, a novel blood based perfusion technology wasdeveloped to keep a liver alive and metabolically active outside of the bodyfor at least one week. Within thismanuscript, we present and compare three scenarios (Group 1, 2 and 3) we werefacing during our research and development (R&D) process, mainly linked tothe measurement of free hemoglobin and lactate in the blood based perfusate. Apartfrom their proven value in liver viability assessment (ex situ), these twoparameters are also helpful in R&D of a long-term liver perfusion machine and moreover supportive in the biomedical engineering process. Group 1 ("good" liver on the perfusion machine) represents the best liver clearance capacity for lactate and free hemoglobin wehave observed. In contrast to Group 2 ("poor" liver on the perfusion machine), that has shown the worst clearance capacity for free hemoglobin. Astonishingly,also for Group 2, lactate is cleared till the first day of perfusion andafterwards, rising lactate values are detected due to the poor quality of theliver. These two perfusate parametersclearly highlight the impact of the organ quality/viability on the perfusion process. Whereas Group 3 is a perfusion utilizing a blood loop only (without a liver). Knowing the feasible ranges (upper- and lower bound) and the courseover time of free hemoglobin and lactate is helpful to evaluate the quality ofthe organ perfusion itself and the maturity of the developed perfusion device. Freehemoglobin in the perfusate is linked to the rate of hemolysis that indicates how optimizing (gentle blood handling, minimizing hemolysis) the perfusion machine actually is. Generally, a reduced lactate clearancecapacity can be an indication for technical problems linked to the blood supplyof the liver and therefore helps to monitor the perfusion experiments.Moreover, the possibility is given to compare, evaluate and optimize developed liverperfusion systems based on the given ranges for these two parameters. Otherresearch groups can compare/quantify their perfusate (blood) parameters withthe ones in this manuscript. The presented data, findings and recommendations willfinally support other researchers in developing their own perfusion machine ormodifying commercially availableperfusion devices according to their needs.

Sections du résumé

BACKGROUND BACKGROUND
Ex situliver machine perfusion at subnormothermic/normothermic temperature isincreasingly applied in the field of transplantation to store and evaluateorgans on the machine prior transplantation. Currently, various perfusionconcepts are in clinical and preclinical applications. Over the last 6 years ina multidisciplinary team, a novel blood based perfusion technology wasdeveloped to keep a liver alive and metabolically active outside of the bodyfor at least one week.
METHODS METHODS
Within thismanuscript, we present and compare three scenarios (Group 1, 2 and 3) we werefacing during our research and development (R&D) process, mainly linked tothe measurement of free hemoglobin and lactate in the blood based perfusate. Apartfrom their proven value in liver viability assessment (ex situ), these twoparameters are also helpful in R&D of a long-term liver perfusion machine and moreover supportive in the biomedical engineering process.
RESULTS RESULTS
Group 1 ("good" liver on the perfusion machine) represents the best liver clearance capacity for lactate and free hemoglobin wehave observed. In contrast to Group 2 ("poor" liver on the perfusion machine), that has shown the worst clearance capacity for free hemoglobin. Astonishingly,also for Group 2, lactate is cleared till the first day of perfusion andafterwards, rising lactate values are detected due to the poor quality of theliver. These two perfusate parametersclearly highlight the impact of the organ quality/viability on the perfusion process. Whereas Group 3 is a perfusion utilizing a blood loop only (without a liver).
CONCLUSION CONCLUSIONS
Knowing the feasible ranges (upper- and lower bound) and the courseover time of free hemoglobin and lactate is helpful to evaluate the quality ofthe organ perfusion itself and the maturity of the developed perfusion device. Freehemoglobin in the perfusate is linked to the rate of hemolysis that indicates how optimizing (gentle blood handling, minimizing hemolysis) the perfusion machine actually is. Generally, a reduced lactate clearancecapacity can be an indication for technical problems linked to the blood supplyof the liver and therefore helps to monitor the perfusion experiments.Moreover, the possibility is given to compare, evaluate and optimize developed liverperfusion systems based on the given ranges for these two parameters. Otherresearch groups can compare/quantify their perfusate (blood) parameters withthe ones in this manuscript. The presented data, findings and recommendations willfinally support other researchers in developing their own perfusion machine ormodifying commercially availableperfusion devices according to their needs.

Identifiants

pubmed: 36106378
doi: 10.1111/aor.14403
doi:

Substances chimiques

Lactates 0
Hemoglobins 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

317-329

Subventions

Organisme : Helmut Horten Foundation
Organisme : PROMEDICA Foundation
Organisme : Wyss Zurich

Informations de copyright

© 2022 International Center for Artificial Organ and Transplantation (ICAOT) and Wiley Periodicals LLC.

Références

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Auteurs

Martin J Schuler (MJ)

Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland.

Dustin Becker (D)

Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland.

Matteo Mueller (M)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

Lucia Bautista Borrego (L)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

Leandro Mancina (L)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

Florian Huwyler (F)

Macromolecular Engineering Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.

Jonas Binz (J)

Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland.

Catherine Hagedorn (C)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

Beatrice Schär (B)

Entwicklung biomedizinische Anwendungen, Securecell AG, Urdorf, Switzerland.

Erich Gygax (E)

Forschung und Entwicklung, Fumedica AG, Muri, Switzerland.

Miriam Weisskopf (M)

Center of Surgical Research, University Hospital Zürich, University of Zürich, Zurich, Switzerland.

Richard Xavier Sousa Da Silva (RX)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

João Miguel Antunes Crisóstomo (JM)

Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland.

Philipp Dutkowski (P)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

Philipp Rudolf von Rohr (P)

Transport Processes and Reactions Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.

Pierre-Alain Clavien (PA)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

Mark W Tibbitt (MW)

Macromolecular Engineering Laboratory, Department of Mechanical and Process Engineering, ETH Zurich, Zurich, Switzerland.

Dilmurodjon Eshmuminov (D)

Department of Surgery, Swiss Hepato-Pancreato-Biliary and Transplantation Center, University Hospital Zurich, Zurich, Switzerland.

Max Hefti (M)

Wyss Zurich - ETH Zurich/University of Zurich, Zurich, Switzerland.

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