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Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model.
Transplantation. 2020 04; 104(4):731-743.T

Abstract

BACKGROUND

The optimal perfusate partial pressure of oxygen (PO2) during hypothermic machine perfusion (HMP) is unknown. The aims of the study were to determine the functional, metabolic, structural, and flow dynamic effects of low and high perfusate PO2 during continuous HMP in a pig kidney ischemia-reperfusion autotransplant model.

METHODS

The left kidneys of a ±40 kg pigs were exposed to 30 minutes of warm ischemia and randomized to receive 22-hour HMP with either low perfusate PO2 (30% oxygen, low oxygenated HMP [HMPO2]) (n = 8) or high perfusate PO2 (90% oxygen, HMPO2high) (n = 8), before autotransplantation. Kidneys stored in 22-hour standard HMP (n = 6) and 22-hour static cold storage (n = 6) conditions served as controls. The follow-up after autotransplantation was 13 days.

RESULTS

High PO2 resulted in a 3- and 10-fold increase in perfusate PO2 compared with low HMPO2 and standard HMP, respectively. Both HMPO2 groups were associated with superior graft recovery compared with the control groups. Oxygenation was associated with a more rapid and sustained decrease in renal resistance. While there was no difference in functional outcomes between both HMPO2 groups, there were clear metabolic differences with an inverse correlation between oxygen provision and the concentration of major central metabolites in the perfusion fluid but no differences were observed by oxidative stress and metabolic evaluation on preimplantation biopsies.

CONCLUSIONS

While this animal study does not demonstrate any advantages for early graft function for high perfusate PO2, compared with low perfusate PO2, perfusate metabolic profile analysis suggests that aerobic mechanism is better supported under high perfusate PO2 conditions.

Authors+Show Affiliations

Department of Surgery, Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université catholique de Louvain, Brussels, Belgium. Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Chirurgie Expérimentale et Transplantation, Université catholique de Louvain, Brussels, Belgium.Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Chirurgie Expérimentale et Transplantation, Université catholique de Louvain, Brussels, Belgium.The Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.Department of Renal Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.Department of Morphology, Experimental and Clinical Research Institute, Université catholique de Louvain, Brussels, Belgium.Department of Pharmacology and Therapeutics, Experimental and Clinical Research Institute, Université catholique de Louvain, Brussels, Belgium.Department of Pathology, University Clinics Saint Luc, Université catholique de Louvain, Brussels, Belgium.Walloon Excellence in Life Sciences and Biotechnology (WELBIO), Institut de Duve, Université catholique de Louvain, Brussels, Belgium.Department of Surgery, Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université catholique de Louvain, Brussels, Belgium. Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Chirurgie Expérimentale et Transplantation, Université catholique de Louvain, Brussels, Belgium.Department of Surgery, Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université catholique de Louvain, Brussels, Belgium.Department of Renal Surgery, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.The Institute of Metabolism and Systems Research (IMSR), College of Medical and Dental Sciences, University of Birmingham, Birmingham, United Kingdom.Department 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.Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Chirurgie Expérimentale et Transplantation, Université catholique de Louvain, Brussels, Belgium.Department of Surgery, Surgery and Abdominal Transplant Unit, University Clinics Saint Luc, Université catholique de Louvain, Brussels, Belgium. Institut de Recherche Expérimentale et Clinique (IREC), Pôle de Chirurgie Expérimentale et Transplantation, Université catholique de Louvain, Brussels, Belgium.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31764761

Citation

Darius, Tom, et al. "Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model." Transplantation, vol. 104, no. 4, 2020, pp. 731-743.
Darius T, Vergauwen M, Smith TB, et al. Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model. Transplantation. 2020;104(4):731-743.
Darius, T., Vergauwen, M., Smith, T. B., Patel, K., Craps, J., Joris, V., Aydin, S., Ury, B., Buemi, A., De Meyer, M., Nath, J., Ludwig, C., Dessy, C., Many, M. C., Gianello, P., & Mourad, M. (2020). Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model. Transplantation, 104(4), 731-743. https://doi.org/10.1097/TP.0000000000003051
Darius T, et al. Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model. Transplantation. 2020;104(4):731-743. PubMed PMID: 31764761.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Influence of Different Partial Pressures of Oxygen During Continuous Hypothermic Machine Perfusion in a Pig Kidney Ischemia-reperfusion Autotransplant Model. AU - Darius,Tom, AU - Vergauwen,Martial, AU - Smith,Thomas B, AU - Patel,Kamlesh, AU - Craps,Julie, AU - Joris,Virginie, AU - Aydin,Selda, AU - Ury,Benoît, AU - Buemi,Antoine, AU - De Meyer,Martine, AU - Nath,Jay, AU - Ludwig,Christian, AU - Dessy,Chantal, AU - Many,Marie-Christine, AU - Gianello,Pierre, AU - Mourad,Michel, PY - 2019/11/26/pubmed PY - 2019/11/26/medline PY - 2019/11/26/entrez SP - 731 EP - 743 JF - Transplantation JO - Transplantation VL - 104 IS - 4 N2 - BACKGROUND: The optimal perfusate partial pressure of oxygen (PO2) during hypothermic machine perfusion (HMP) is unknown. The aims of the study were to determine the functional, metabolic, structural, and flow dynamic effects of low and high perfusate PO2 during continuous HMP in a pig kidney ischemia-reperfusion autotransplant model. METHODS: The left kidneys of a ±40 kg pigs were exposed to 30 minutes of warm ischemia and randomized to receive 22-hour HMP with either low perfusate PO2 (30% oxygen, low oxygenated HMP [HMPO2]) (n = 8) or high perfusate PO2 (90% oxygen, HMPO2high) (n = 8), before autotransplantation. Kidneys stored in 22-hour standard HMP (n = 6) and 22-hour static cold storage (n = 6) conditions served as controls. The follow-up after autotransplantation was 13 days. RESULTS: High PO2 resulted in a 3- and 10-fold increase in perfusate PO2 compared with low HMPO2 and standard HMP, respectively. Both HMPO2 groups were associated with superior graft recovery compared with the control groups. Oxygenation was associated with a more rapid and sustained decrease in renal resistance. While there was no difference in functional outcomes between both HMPO2 groups, there were clear metabolic differences with an inverse correlation between oxygen provision and the concentration of major central metabolites in the perfusion fluid but no differences were observed by oxidative stress and metabolic evaluation on preimplantation biopsies. CONCLUSIONS: While this animal study does not demonstrate any advantages for early graft function for high perfusate PO2, compared with low perfusate PO2, perfusate metabolic profile analysis suggests that aerobic mechanism is better supported under high perfusate PO2 conditions. SN - 1534-6080 UR - https://www.unboundmedicine.com/medline/citation/31764761/Influence_of_Different_Partial_Pressures_of_Oxygen_During_Continuous_Hypothermic_Machine_Perfusion_in_a_Pig_Kidney_Ischemia_reperfusion_Autotransplant_Model_ L2 - https://doi.org/10.1097/TP.0000000000003051 DB - PRIME DP - Unbound Medicine ER -
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