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Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model.
Am J Transplant. 2020 Aug; 20(8):2030-2043.AJ

Abstract

With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, nonoxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (eg, lactate, succinate, flavin mononucleotide) and tissues (eg, succinate, adenosine triphosphate, hypoxia-inducible factor-1α, nuclear factor erythroid 2-related factor 2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O2 uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria, and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation.

Authors+Show Affiliations

Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université Catholique de Louvain, Brussels, Belgium. Pole de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.Pole de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.The Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, UK.Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Laboratory of Physiological Chemistry, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.Pole of Pharmacology and Therapeutics, Experimental and Clinical Research Institute, Université Catholique de Louvain, Brussels, Belgium.Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland.Department of Pathology, University Clinics Saint Luc, Université Catholique de Louvain, Brussels, Belgium.Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland.Liver Unit, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham, Birmingham, UK.Department of Renal Transplantation, Southmead Hospital Bristol, Bristol, UK.The Institute of Metabolism and Systems Research (IMSR), University of Birmingham, Birmingham, UK.Pole of Pharmacology and Therapeutics, Experimental and Clinical Research Institute, Université Catholique de Louvain, Brussels, Belgium.Department of Morphology, Experimental and Clinical Research Institute, Université Catholique de Louvain, Brussels, Belgium.Walloon Excellence in Lifesciences and Biotechnology (WELBIO), Laboratory of Physiological Chemistry, de Duve Institute, Université Catholique de Louvain, Brussels, Belgium.Department of Surgery and Transplantation, Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland.Pole de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université Catholique de Louvain, Brussels, Belgium. Pole de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32012434

Citation

Darius, Tom, et al. "Brief O2 Uploading During Continuous Hypothermic Machine Perfusion Is Simple yet Effective Oxygenation Method to Improve Initial Kidney Function in a Porcine Autotransplant Model." American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, vol. 20, no. 8, 2020, pp. 2030-2043.
Darius T, Vergauwen M, Smith T, et al. Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model. Am J Transplant. 2020;20(8):2030-2043.
Darius, T., Vergauwen, M., Smith, T., Gerin, I., Joris, V., Mueller, M., Aydin, S., Muller, X., Schlegel, A., Nath, J., Ludwig, C., Dessy, C., Many, M. C., Bommer, G., Dutkowski, P., Gianello, P., & Mourad, M. (2020). Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model. American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons, 20(8), 2030-2043. https://doi.org/10.1111/ajt.15800
Darius T, et al. Brief O2 Uploading During Continuous Hypothermic Machine Perfusion Is Simple yet Effective Oxygenation Method to Improve Initial Kidney Function in a Porcine Autotransplant Model. Am J Transplant. 2020;20(8):2030-2043. PubMed PMID: 32012434.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brief O2 uploading during continuous hypothermic machine perfusion is simple yet effective oxygenation method to improve initial kidney function in a porcine autotransplant model. AU - Darius,Tom, AU - Vergauwen,Martial, AU - Smith,Thomas, AU - Gerin,Isabelle, AU - Joris,Virginie, AU - Mueller,Matteo, AU - Aydin,Selda, AU - Muller,Xavier, AU - Schlegel,Andrea, AU - Nath,Jay, AU - Ludwig,Christian, AU - Dessy,Chantal, AU - Many,Marie-Christine, AU - Bommer,Guido, AU - Dutkowski,Philipp, AU - Gianello,Pierre, AU - Mourad,Michel, Y1 - 2020/02/21/ PY - 2019/11/24/received PY - 2020/01/23/revised PY - 2020/01/24/accepted PY - 2020/2/6/pubmed PY - 2020/2/6/medline PY - 2020/2/4/entrez KW - animal models: porcine KW - autotransplantation KW - ischemia-reperfusion injury (IRI) KW - kidney (allograft) function/dysfunction KW - kidney transplantation/nephrology KW - organ perfusion and preservation KW - organ procurement and allocation KW - translational research/science SP - 2030 EP - 2043 JF - American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons JO - Am. J. Transplant. VL - 20 IS - 8 N2 - With oxygenation proposed as a resuscitative measure during hypothermic models of preservation, the aim of this study was to evaluate the optimal start time of oxygenation during continuous hypothermic machine perfusion (HMP). In this porcine ischemia-reperfusion autotransplant model, the left kidney of a ±40 kg pig was exposed to 30 minutes of warm ischemia prior to 22 hours of HMP and autotransplantation. Kidneys were randomized to receive 2 hours of oxygenation during HMP either at the start (n = 6), or end of the perfusion (n = 5) and outcomes were compared to standard, nonoxygenated HMP (n = 6) and continuous oxygenated HMP (n = 8). The brief initial and continuous oxygenated HMP groups were associated with superior graft recovery compared to either standard, nonoxygenated HMP or kidneys oxygenated at the end of HMP. This correlated with significant metabolic differences in perfusate (eg, lactate, succinate, flavin mononucleotide) and tissues (eg, succinate, adenosine triphosphate, hypoxia-inducible factor-1α, nuclear factor erythroid 2-related factor 2) suggesting superior mitochondrial preservation with initial oxygenation. Brief initial O2 uploading during HMP at procurement site might be an easy and effective preservation strategy to maintain aerobic metabolism, protect mitochondria, and achieve an improved early renal graft function compared with standard HMP or oxygen supply shortly at the end of HMP preservation. SN - 1600-6143 UR - https://www.unboundmedicine.com/medline/citation/32012434/Brief_O2_uploading_during_continuous_hypothermic_machine_perfusion_is_simple_yet_effective_oxygenation_method_to_improve_initial_kidney_function_in_a_porcine_autotransplant_model_ L2 - https://doi.org/10.1111/ajt.15800 DB - PRIME DP - Unbound Medicine ER -
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