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1. SAPHIR - a multi-scale, multi-resolution modeling environment targeting blood pressure regulation and fluid homeostasis

Author

Thomas, S. Randall, Abdulhay, Enas, Baconnier, Pierre, Fontecave, Julie, Francoise, Jean-Pierre, Guillaud, Francois, Hannaert, Patrick, Hernandez, Alfredo, Rolle, Virginie Le, Maziere, Pierre, Tahi, Fariza, and Zehraoui, Farida

Subjects
Quantitative Biology - Tissues and Organs
Abstract

We present progress on a comprehensive, modular, interactive modeling environment centered on overall regulation of blood pressure and body fluid homeostasis. We call the project SAPHIR, for "a Systems Approach for PHysiological Integration of Renal, cardiac, and respiratory functions". The project uses state-of-the-art multi-scale simulation methods. The basic core model will give succinct input-output (reduced-dimension) descriptions of all relevant organ systems and regulatory processes, and it will be modular, multi-resolution, and extensible, in the sense that detailed submodules of any process(es) can be "plugged-in" to the basic model in order to explore, eg. system-level implications of local perturbations. The goal is to keep the basic core model compact enough to insure fast execution time (in view of eventual use in the clinic) and yet to allow elaborate detailed modules of target tissues or organs in order to focus on the problem area while maintaining the system-level regulatory compensations.

Published
2008
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3. Impact of Red Blood Cells on Function and Metabolism of Porcine Deceased Donor Kidneys During Normothermic Machine Perfusion

Author

Venema, Leonie H, van Leeuwen, L Leonie, Posma, Rene A, van Goor, Harry, Ploeg, Rutger J, Hannaert, Patrick, Hauet, Thierry, Minor, Thomas, Leuvenink, Henri G D, COPE Consortium, Groningen Institute for Organ Transplantation (GIOT), and Groningen Kidney Center (GKC)

Subjects
Erythrocytes, Swine, Medizin, Renal function, medicine.disease_cause, Kidney, DEXTRAN, Andrology, COLD-STORAGE, medicine, INJURY, Animals, REPERFUSION, PRESERVATION, Bovine serum albumin, Deceased donor, Machine perfusion, biology, Chemistry, TRANSPLANTATION, CONSUMPTION, Metabolism, Organ Preservation, Kidney Transplantation, COLLOIDS, Transplantation, Perfusion, biology.protein, DONATION, REABSORPTION, Oxidative stress, Biomarkers
Abstract

BackgroundNormothermic machine perfusion (NMP) protocols using blood-based solutions are commonly used in the assessment of kidneys before transplantation. This procedure is, nevertheless, limited by blood availability and warrants the search for alternatives. We compared a blood-based solution with a serum-like preservation solution (Aqix) enriched with colloids with and without red blood cells (RBCs).MethodsPorcine kidneys retrieved from an abattoir were subjected to 30 min of warm ischemia, followed by 3 h of hypothermic oxygenated machine perfusion at 4 °C. Subsequently, kidneys (n = 6 per group) were evaluated with NMP for 4 h with 5 different solutions: diluted blood, Aqix with BSA ± RBCs, or Aqix with dextran 40 ± RBCs.ResultsThroughout NMP, markers of renal function and tubular metabolism were favorable in groups with RBCs. The addition of RBCs resulted in 4- to 6-fold higher oxygen consumption rates. Controls had significantly higher ATP levels post-NMP, exhibited decreased production of oxidative stress markers, and had the highest creatinine clearance. In conclusion, this study shows that the addition of RBCs during NMP reduced renal injury, improved function, and was associated with increased renal metabolism.ConclusionsAlthough the RBC-BSA-supplemented Aqix solution was also able to support metabolism and renal function, a blood-based perfusion solution remains superior.

Published
2022

7. Author response for 'No more hypoglycaemia on days with physical activity and unrestricted diet when using a closed-loop system for 12 weeks: A post hoc secondary analysis of the multicentre, randomized controlled Diabeloop WP7 trial'

Author

null Franc, Sylvia, null Benhamou, Pierre-Yves, null Borot, Sophie, null Chaillous, Lucy, null Delemer, Brigitte, null Doron, Maeva, null Guerci, Bruno, null Hanaire, Helene, null Huneker, Erik, null Jeandidier, Nathalie, null Amadou, Coralie, null Renard, Eric, null Reznik, Yves, null Schaepelynck, Pauline, null Simon, Chantal, null Thivolet, Charles, null Thomas, Claire, null Hannaert, Patrick, and null Charpentier, Guillaume

Published
2021

9. No more hypoglycaemia on days with physical activity and unrestricted diet when using a closed‐loop system for 12 weeks: A post hoc secondary analysis of the multicentre, randomized controlled Diabeloop WP7 trial

Author

Franc, Sylvia, primary, Benhamou, Pierre‐Yves, additional, Borot, Sophie, additional, Chaillous, Lucy, additional, Delemer, Brigitte, additional, Doron, Maeva, additional, Guerci, Bruno, additional, Hanaire, Hélène, additional, Huneker, Erik, additional, Jeandidier, Nathalie, additional, Amadou, Coralie, additional, Renard, Eric, additional, Reznik, Yves, additional, Schaepelynck, Pauline, additional, Simon, Chantal, additional, Thivolet, Charles, additional, Thomas, Claire, additional, Hannaert, Patrick, additional, and Charpentier, Guillaume, additional

Published
2021
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13. A Computer Model of Oxygen Dynamics in the Cortex of the Rat Kidney at the Cell-Tissue Level

Author

Aubert, Vivien, Kaminski, Jacques, Guillaud, François, Hauet, Thierry, Hannaert, Patrick, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers

Subjects
kidney, Na reabsorption, proximal tubule, [SDV.IB]Life Sciences [q-bio]/Bioengineering, renal cortex, rat, peritubular capillary, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, hemoglobin, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], oxygen, oxygen consumption, agent-based model
Abstract

The renal cortex drives renal function. Hypoxia/reoxygenation are primary factors in ischemia-reperfusion (IR) injuries, but renal oxygenation per se is complex and awaits full elucidation. Few mathematical models address this issue: none captures cortical tissue heterogeneity. Using agent-based modeling, we develop the first model of cortical oxygenation at the cell-tissue level (RCM), based on first principles and careful bibliographical analysis. Entirely parameterized with Rat data, RCM is a morphometrically equivalent 2D-slice of cortical tissue, featuring peritubular capillaries (PTC), tubules and interstitium. It implements hemoglobin/O2 binding-release, oxygen diffusion, and consumption, as well as capillary and tubular flows. Inputs are renal blood flow RBF and PO2 feeds, output is average tissue PO2 (tPO2). After verification and sensitivity analysis, RCM was validated at steady-state (tPO2 37.7 &plusmn, 2.2 vs. 36.9 &plusmn, 6 mmHg) and under transients (ischemic oxygen half-time: 4.5 &plusmn, 2.5 vs. 2.3 &plusmn, 0.5 s in situ). Simulations confirm that PO2 is largely independent of RBF, except at low values. They suggest that, at least in the proximal tubule, the luminal flow dominantly contributes to oxygen delivery, while the contribution of capillaries increases under partial ischemia. Before addressing IR-induced injuries, upcoming developments include ATP production, adaptation to minutes&ndash, hours scale, and segmental and regional specification.

Published
2019
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16. Efficacy of Diabeloop closed‐loop to improve glycaemic control in patients with type 1 diabetes exposed to copious dinners or to sustained physical exercise

Author

Hanaire, Hélène, Franc, Sylvia, Borot, Sophie, Penfornis, Alfred, Benhamou, Pierre‐Yves, Schaepelynck, Pauline, Renard, Eric, Guerci, Bruno, Jeandidier, Nathalie, Simon, Chantal, Hannaert, Patrick, Xhaard, Ilham, Doron, Maeva, Huneker, Erik, Charpentier, Guillaume, Reznik, Yves, Service Diabétologie [CHU Toulouse], Pôle Cardiovasculaire et Métabolique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Diabétologie, Hôpital Sud Francilien Corbeil Essonne, Service de Diabétologie - Endocrinologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), CIC Montpellier, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Strasbourg, Régulations métaboliques, nutrition et diabètes - UM55 (RMND UM55), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), DIABELOOP S.A., Centre d'études et de recherches pour l'intensification du traitement du diabète (CERITD), Service d'endocrinologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Diabétologie - Maladies Métaboliques - Nutrition, CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de diabétologie - endocrinologie, Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Eloi, Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Laboratoire d'Electronique et des Technologies de l'Information (CEA-LETI), Université Grenoble Alpes (UGA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-CHU Saint-Eloi-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
[SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2019

17. Efficacy of the natural oxygen transporter HEMO 2 life ® in cold preservation in a preclinical porcine model of donation after cardiac death

Author

Kaminski, Jacques, Hannaert, Patrick, Kasil, Abdelsalam, Thuillier, Raphael, Leize, Elisabeth, Delpy, Eric, Steichen, Clara, Goujon, Jean Michel, Zal, Franck, Hauet, Thierry, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Service de Biochimie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), HEMARINA SA, Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation (FHU SUPORT), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours-Université de Tours, Département Génétique Animale (DEPT GA), Institut National de la Recherche Agronomique (INRA), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cellules Dendritiques, Immunomodulation et Greffes, and Université de Tours (UT)-Université de Tours (UT)

Subjects
ischemia reperfusion injury, graft preservation, oxygen carrier, hypotermic machine perfusion, kidney transplantation, donation after circulatory death, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, oxygen, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], ComputingMilieux_MISCELLANEOUS, cold preservation, static cold storage
Abstract

International audience; The growing use of marginal organs for transplantation pushes current preservation methods toward their limits, and the need for improvement is pressing. We previously demonstrated the benefits of M101, a natural extracellular oxygen carrier compatible with hypothermia, for the preservation of healthy renal grafts in a porcine model of autotransplantation. Herein, we use a variant of this preclinical model to evaluate M101 potential benefits both in static cold storage (CS) and in machine perfusion (MP) preservation in the transplantation outcomes for marginal kidneys. In the CS arm, despite the absence of obvious benefits within the first 2 weeks of follow-up, M101 dose-dependently improved long-term function, normalizing creatininemia after 1 and 3 months. In the MP arm, M101 improved short- and long-term functional outcomes as well as tissue integrity. Importantly, we provide evidence for the additivity of MP and M101 functional effects, showing that the addition of the compound further improves organ preservation, by reducing short-term function loss, with no loss of function or tissue integrity recorded throughout the follow-up. Extending previous observations with healthy kidneys, the present results point at the M101 oxygen carrier as a viable strategy to improve current organ preservation methods in marginal organ transplantation.

Published
2019

18. Dynamic transcriptomic analysis of ischemic injury in a porcine pre-clinical model mimicking donors deceased after circulatory death

Author

Giraud, Sebastien, Steichen, Clara, Allain, Geraldine, Couturier, Pierre, Labourdette, Delphine, Lamarre, Sophie, Ameteau, Virginie, Tillet, Solenne, Hannaert, Patrick, Thuillier, Raphael, Hauet, Thierry, U1082, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Service de chirurgie cardio‐thoracique, Centre Hospitalier Universitaire de Poitiers (CHU de Poitiers), Innovation Chirurgicale et Technologique - Ibisa Plateforme Experimental Surgery and Transplantation, MOdélisation Préclinique - Innovation Chirurgicale et Technologique (MOPICT), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Groupement Scientifique - Ibisa (Ibisa), Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Groupement Scientifique - Ibisa (IBISA), Service de Biochimie, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]

Subjects
renal pelvis, [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, donneur, Down-Regulation, lcsh:Medicine, Kidney, Cardiovascular System, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, Article, ischémie reperfusion, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], crise cardiaque, Urology and Nephrology, Animals, Warm Ischemia, lcsh:Science, donor, Urologie et Néphrologie, lcsh:R, rein, swine, Organ Preservation, Kidney Transplantation, Tissue Donors, Agricultural sciences, étude transcriptomique, Death, Reperfusion Injury, lcsh:Q, Transcriptome, Sciences agricoles, Biomarkers, stress ischémique, porc
Abstract

Présenté au: 18. Annual Congress of the French Speaking Transplantation SocietyToulouse FranceDate: 4 au 7 décembre 2018; International audience; Introduction: Due to organ shortage, clinicians are prone to consider alternative type of organ donors among them donors deceased after circulatory death (DCD). However, especially using these organs which are more prone to graft dysfunction, there is a need to better understand mechanistic events occurring during ischemia phase and leading to ischemia/reperfusion injuries (IRI). The aim of this study is to provide a dynamic transcriptomic analysis of preclinical porcine model kidneys subjected to ischemic stress mimicking DCD donor.Methods: We compared cortex and corticomedullary junction (CMJ) tissues from porcine kidneys submitting to 60 min warm ischemia (WI) followed by 0, 6 or 24 h of cold storage in University of Wisconsin solution versus control non‐ischemic kidneys (n = 5 per group).Results: 29 cortex genes and 113 CMJ genes were significantly up or down‐regulated after WI versus healthy kidneys, and up to 400 genes were regulated after WI and more 6 or 24 h of cold storage (p < 0.05). Home selected gene kinetic classification, Gene‐ontology‐biological processes and Gene‐ontology‐molecular‐function functional enrichment analysis revealed relevant genes implication during WI and cold storage.Conclusion: We uncovered targets which we will further validate as biomarkers and new therapeutic targets to optimize graft kidney quality before transplantation and improve whole transplantation outcome.

Published
2019

25. Efficacy of the Diabeloop closed‐loop system to improve glycaemic control in patients with type 1 diabetes exposed to gastronomic dinners or to sustained physical exercise

Author

Hanaire, Hélène, primary, Franc, Sylvia, additional, Borot, Sophie, additional, Penfornis, Alfred, additional, Benhamou, Pierre‐Yves, additional, Schaepelynck, Pauline, additional, Renard, Eric, additional, Guerci, Bruno, additional, Jeandidier, Nathalie, additional, Simon, Chantal, additional, Hannaert, Patrick, additional, Xhaard, Ilham, additional, Doron, Maeva, additional, Huneker, Erik, additional, Charpentier, Guillaume, additional, and Reznik, Yves, additional

Published
2019
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30. Controlled oxygenated rewarming up to normothermia for pretransplant reconditioning of liver grafts

Author

Hannaert, Patrick, von Horn, Charlotte, Baba, Hideo, Hannaert, Patrik, Hauet, Thierry, Leuvenink, Henri, Paul, Andreas, Minor, Thomas, Essen University Hospital, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, University Medical Center Groningen [Groningen] (UMCG), Groningen Institute for Organ Transplantation (GIOT), IRTOMIT, INSERM, Université de Médecine et de Pharmacie de Poitiers, Poitiers, France, Department for Surgical Research, General Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany, and Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, ORGAN PRESERVATION, medicine.medical_treatment, organ reconditioning, [SDV]Life Sciences [q-bio], Medizin, RAT-LIVER, Cold storage, controlled oxygenated rewarming, 030230 surgery, Liver transplantation, liver preservation, MECHANISMS, 03 medical and health sciences, 0302 clinical medicine, COLD-STORAGE, medicine, INJURY, Animals, REPERFUSION, Rats, Wistar, Rewarming, CIRCULATORY DEATH, Liver preservation, TEMPERATURE, ComputingMilieux_MISCELLANEOUS, Transplantation, Machine perfusion, business.industry, machine perfusion, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Liver Transplantation, Rats, Oxygen, Perfusion, Reperfusion Injury, Anesthesia, KIDNEYS, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 030211 gastroenterology & hepatology, business, Reperfusion injury, Ex vivo, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Controlled oxygenated rewarming (COR) up to 20 degrees C during ex vivo machine perfusion limits reperfusion-induced tissue injury upon graft implantation. Rewarming up to normothermia might add further benefits and provide better prediction of post-transplantation organ function. The effect of 90 minutes of oxygenated machine perfusion with Aqix RS-I after cold storage combined with gentle rewarming up to 20 degrees C (COR20) or 35 degrees C (COR35) was studied in rat livers and compared with cold storage alone (CS, n = 6, resp). Postpreservation recovery was evaluated upon warm reperfusion using an established in vitro system. COR generally resulted in significantly improved energetic recovery, increased bile flow, less activities alanine aminotransferase (ALT) release, and improved histopathology upon reperfusion as compared to only cold-stored livers, without significant differences between COR20 and COR35. Parameters obtained during COR, especially during COR35, also allowed for prediction of hepatic recovery upon reperfusion. For instance, ulterior bile production upon reperfusion was found closely correlated to bile flow observed already during COR35 (R-2=0.91). COR significantly improved liver quality after static cold storage. Elevation of machine perfusion temperature up to 35 degrees C may prove promising to refine ex vivo evaluation of the graft prior to transplantation.

Published
2017

31. Renal auto-transplantation promotes cortical microvascular network remodeling in a preclinical porcine model

Author

Maïga, Souleymane, Allain, Geraldine, Hauet, Thierry, Roumy, Jerome, Baulier, Edouard, Scepi, Michel, Dierick, Manuel, van Hoorebeke, Luc, Hannaert, Patrick, Guy, Franck, Favreau, Frédéric, Camussi, Giovanni, Pinet, Nicolas, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, CHU de Bordeaux Pellegrin [Bordeaux], CHU Poitiers, Service de chirurgie cardio-thoracique, Poitiers, 86000, France, Service de Biochimie [Poitiers], Centre hospitalier universitaire de Poitiers (CHU Poitiers), Génétique, Expérimentation et Système Innovants (GenESI), Institut National de la Recherche Agronomique (INRA), Fédération Hospitalo-universitaire SUrvival oPtimization in ORgan Transplantation (FHU SUPORT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours (UT)-Université de Tours (UT)-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universiteit Gent = Ghent University (UGENT), Center for X-ray Tomography [Ghent] (UGCT), Department of Physics and Astronomy [Ghent], Universiteit Gent = Ghent University (UGENT)-Universiteit Gent = Ghent University (UGENT), Institut International de Paléoprimatologie, Paléontologie Humaine : Evolution et Paléoenvironnement (IPHEP), Université de Poitiers-Centre National de la Recherche Scientifique (CNRS), Università degli studi di Torino = University of Turin (UNITO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Ciblage individuel et prévention des risques de traitements immunosupresseurs et de la transplantation (IPPRITT), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut National de la Santé et de la Recherche Médicale (INSERM)- Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Cellules Dendritiques, Immunomodulation et Greffes, Université de Tours-Université de Tours, Ghent University [Belgium] (UGENT), Ghent University [Belgium] (UGENT)-Ghent University [Belgium] (UGENT), Centre National de la Recherche Scientifique (CNRS)-Université de Poitiers, Università degli studi di Torino (UNITO), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM)-Cellules Dendritiques, Immunomodulation et Greffes, Universiteit Gent = Ghent University [Belgium] (UGENT), Universiteit Gent = Ghent University [Belgium] (UGENT)-Universiteit Gent = Ghent University [Belgium] (UGENT), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Anti-infectieux : supports moléculaires des résistances et innovations thérapeutiques (RESINFIT), and Université de Tours (UT)-Université de Tours (UT)

Subjects
modèle animal, Physiology, Swine, lcsh:Medicine, Kidney, Vascular Medicine, HYPERCHOLESTEROLEMIA, Ischemia, Animal Cells, Blood Flow, Medicine and Health Sciences, Renal Transplantation, FAILURE, lcsh:Science, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Graft Survival, rein, transplantation d'organe, cochon, Organ Preservation, Body Fluids, Blood, Reperfusion Injury, PIG KIDNEYS, Anatomy, Cellular Types, Renal Ischemia, Research Article, LONG-TERM, Excretion, Surgical and Invasive Medical Procedures, Transplantation, Autologous, Urinary System Procedures, Animals, Humans, ALLOGRAFT-REJECTION, ENDOTHELIAL INJURY, Transplantation, Blood Cells, TRANSPLANTATION, lcsh:R, Biology and Life Sciences, Kidneys, Renal System, Organ Transplantation, Cell Biology, X-Ray Microtomography, MICROCIRCULATION, Fibrosis, Kidney Transplantation, COLD ISCHEMIA/REPERFUSION, DYSFUNCTION, Disease Models, Animal, Microvessels, lcsh:Q, Physiological Processes, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Developmental Biology
Abstract

International audience; The vascular network is a major target of ischemia-reperfusion, but has been poorly investigated in renal transplantation. The aim of this study was to characterize the remodeling of the renal vascular network that follows ischemia-reperfusion along with the most highly affected cortex section in a preclinical renal transplantation model. There were two experimental groups. The first was a grafted kidney group consisting of large white pigs for which the left kidney was harvested, cold flushed, preserved for 24 h in the University of Wisconsin’s preservation solution, and then auto-transplanted (n = 5); the right kidney was removed to mimic the situation of human kidney transplantation. The second group (uni-nephrectomized kidney group) consisted of animals that underwent only right nephrectomy, but not left renal transplantation (n = 5). Three months after autotransplantation, the kidneys were studied by X-ray microcomputed tomography. Vessel morphology and density and tortuosity of the network were analyzed using a 3D image analysis method. Cortical blood flow was determined by laser doppler analysis and renal function and tissue injury assessed by plasma creatinine levels and histological analysis. Renal ischemia-reperfusion led to decreased vascular segment volume associated with fewer vessels of less than 30 μm, particularly in the inner cortex:0.79 ± 0.54% in grafted kidneys vs. 7.06 ± 1.44% in uni-nephrectomized kidneys, p < 0.05. Vessels showed higher connectivity throughout the cortex (the arborescence factor of the whole cortex was less in grafted than uni-nephrectomized kidneys 0.90 ± 0.04 vs. 1.07 ± 0.05, p < 0.05, with an increase in the number of bifurcations). Furthermore, cortical blood flow decreased early in kidney grafts and remained low three months after auto-transplantation. The decrease in microvasculature correlated with a deterioration of renal function, proteinuria, and tubular dysfunction, and was associated with the development of fibrous tissue. This work provides new evidence concerning the impact of ischemia-reperfusion injuries on the spectrum of renal vascular diseases and could potentially guide future therapy to preserve microvessels in transplantation ischemia-reperfusion injury.

Published
2017

32. Efficacy of the Diabeloop closed‐loop system to improve glycaemic control in patients with type 1 diabetes exposed to gastronomic dinners or to sustained physical exercise.

Author

Hanaire, Hélène, Franc, Sylvia, Borot, Sophie, Penfornis, Alfred, Benhamou, Pierre‐Yves, Schaepelynck, Pauline, Renard, Eric, Guerci, Bruno, Jeandidier, Nathalie, Simon, Chantal, Hannaert, Patrick, Xhaard, Ilham, Doron, Maeva, Huneker, Erik, Charpentier, Guillaume, and Reznik, Yves

Subjects
GLYCEMIC control, TYPE 1 diabetes, EXERCISE, CLOSED loop systems, INGESTION
Abstract

Aims: To compare closed‐loop (CL) and open‐loop (OL) systems for glycaemic control in patients with type 1 diabetes (T1D) exposed to real‐life challenging situations (gastronomic dinners or sustained physical exercise). Methods: Thirty‐eight adult patients with T1D were included in a three‐armed randomized pilot trial (Diabeloop WP6.2 trial) comparing glucose control using a CL system with use of an OL device during two crossover 72‐hour periods in one of the three following situations: large (gastronomic) dinners; sustained and repeated bouts of physical exercise (with uncontrolled food intake); or control (rest conditions). Outcomes included time in spent in the glucose ranges of 4.4‐7.8 mmol/L and 3.9‐10.0 mmol/L, and time in hypo‐ and hyperglycaemia. Results: Time spent overnight in the tight range of 4.4 to 7.8 mmol/L was longer with CL (mean values: 63.2% vs 40.9% with OL; P ≤.0001). Time spent during the day in the range of 3.9 to 10.0 mmol/L was also longer with CL (79.4% vs 64.1% with OL; P ≤.0001). Participants using the CL system spent less time during the day with hyperglycaemic excursions (glucose >10.0 mmol/L) compared to those using an OL system (17.9% vs 31.9%; P ≤.0001), and the proportions of time spent during the day with hyperglycaemic excursions of those using the CL system in the gastronomic dinner and physical exercise subgroups were of similar magnitude to those in the control subgroup (18.1 ± 6.3%, 17.2 ± 8.1% and 18.4 ± 12.5%, respectively). Finally, times spent in hypoglycaemia were short and not significantly different among the groups. Conclusions: The Diabeloop CL system is superior to OL devices in reducing hyperglycaemic excursions in patients with T1D exposed to gastronomic dinners, or exposed to physical exercise followed by uncontrolled food and carbohydrate intake. [ABSTRACT FROM AUTHOR]

Published
2020
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33. Dynamic transcriptomic analysis of Ischemic Injury in a Porcine Pre-Clinical Model mimicking Donors Deceased after Circulatory Death

Author

Giraud, Sebastien, primary, Steichen, Clara, additional, Allain, Geraldine, additional, Couturier, Pierre, additional, Labourdette, Delphine, additional, Lamarre, Sophie, additional, Ameteau, Virginie, additional, Tillet, Solenne, additional, Hannaert, Patrick, additional, Thuillier, Raphael, additional, and Hauet, Thierry, additional

Published
2018
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34. Cell atp and viability alterations induced by ischemia-reperfusion in the renal cortex: an agent-based computer model

Author

Aubert, Vivien, Guillaud, Francois, Hauet, Thierry, Hannaert, Patrick, thuillier raphael, ProdInra, Migration, Ischémie Reperfusion en Transplantation d’Organes Mécanismes et Innovations Thérapeutiques ( IRTOMIT), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), U 0967 Plateforme Ibisa, Université de Poitiers, and European Society for Organ Transplantation (ESOT). INT.

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2015

35. Efficacy of the natural oxygen transporter HEMO2life® in cold preservation in a preclinical porcine model of donation after cardiac death.

Author

Kaminski, Jacques, Hannaert, Patrick, Kasil, Abdelsalam, Thuillier, Raphael, Leize, Elisabeth, Delpy, Eric, Steichen, Clara, Goujon, Jean Michel, Zal, Franck, and Hauet, Thierry

Subjects
*OXYGEN carriers, *TRANSPLANTATION of organs, tissues, etc., *COST functions, *AUTOTRANSPLANTATION, *OXYGEN
Abstract

Summary: The growing use of marginal organs for transplantation pushes current preservation methods toward their limits, and the need for improvement is pressing. We previously demonstrated the benefits of M101, a natural extracellular oxygen carrier compatible with hypothermia, for the preservation of healthy renal grafts in a porcine model of autotransplantation. Herein, we use a variant of this preclinical model to evaluate M101 potential benefits both in static cold storage (CS) and in machine perfusion (MP) preservation in the transplantation outcomes for marginal kidneys. In the CS arm, despite the absence of obvious benefits within the first 2 weeks of follow‐up, M101 dose‐dependently improved long‐term function, normalizing creatininemia after 1 and 3 months. In the MP arm, M101 improved short‐ and long‐term functional outcomes as well as tissue integrity. Importantly, we provide evidence for the additivity of MP and M101 functional effects, showing that the addition of the compound further improves organ preservation, by reducing short‐term function loss, with no loss of function or tissue integrity recorded throughout the follow‐up. Extending previous observations with healthy kidneys, the present results point at the M101 oxygen carrier as a viable strategy to improve current organ preservation methods in marginal organ transplantation. [ABSTRACT FROM AUTHOR]

Published
2019
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36. Cold flush after dynamic liver preservation protects against ischemic changes upon reperfusion – an experimental study.

Author

Horn, Charlotte, Paul, Andreas, Minor, Thomas, Hannaert, Patrick, Hauet, Thierry, and Leuvenink, Henri

Abstract

Summary: Ex vivo machine perfusion of the liver after cold storage has found to be most effective if combined with controlled oxygenated rewarming up to (sub)‐normothermia. On disconnection of the warm graft from the machine, most surgeons usually perform a cold flush of the organ as protection against the second warm ischemia incurred upon implantation. Experimental evidence, however, is lacking and protective effect of deep hypothermia has been challenged for limited periods of liver ischemia in other models. A first systematic test was carried out on porcine livers, excised 30 min after cardiac arrest, subjected to 18 h of cold storage in UW and then machine perfused for 90 min with Aqix‐RSI solution. During machine perfusion, livers were gradually rewarmed up to 20 °C. One group (n = 6) was then reflushed with 4 °C cold Belzer UW solution whereas the second group (n = 6) remained without cold flush. All livers were exposed to 45 min warm ischemia at room temperature to simulate the surgical implantation period. Organ function was evaluated in an established reperfusion model using diluted autologous blood. Cold reflush after disconnection from the machine resulted in a significant increase in bile production upon blood reperfusion, along with a significant reduction in transaminases release alanine aminotransferase and of the intramitochondrial enzyme glutamate dehydrogenase. Interestingly, free radical‐mediated lipid peroxidation was also found significantly lower after cold reflush. No differences between the groups could be evidenced concerning histological injury and recovery of hepatic energy metabolism (tissue content of adenosine triphosphate). Post‐machine preservation cold reflush seems to be beneficial in this particular setting, even if the organs are warmed up only to 20 °C, without notion of adverse effects, and should therefore be implemented in the protocol. [ABSTRACT FROM AUTHOR]

Published
2019
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39. From channelopathies to hypertension: A multi-mode modeling approach for exploration of heterogeneous systems spanning many scales and involving multiple organ systems

Author

Thomas, S. Randall, Baconnier, Pierre, Hannaert, Patrick, Hernandez, Alfredo, Informatique, Biologie Intégrative et Systèmes Complexes (IBISC), Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS), Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Ischémie - Reperfusion en transplatation rénale, Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), SFBT - French Society for Mathematical Biology, and Davesne, Frédéric

Subjects
[SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-GT]Computer Science [cs]/Computer Science and Game Theory [cs.GT], [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [SCCO.COMP]Cognitive science/Computer science, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.UN] Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, [SDV.MHEP.UN]Life Sciences [q-bio]/Human health and pathology/Urology and Nephrology, [SCCO.COMP] Cognitive science/Computer science, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [INFO.INFO-GT] Computer Science [cs]/Computer Science and Game Theory [cs.GT], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], [INFO.INFO-BI] Computer Science [cs]/Bioinformatics [q-bio.QM]
Abstract

Despite the development of ever more sophisticated models at many scales, from the level of gene regulation or intra-cellular signal transduction or cellular metabolism, through models of tissue function, epithelial transport, or even whole organ physiology, there is presently, to our knowledge, no comprehensive, organism-level modeling environment that allows exploration of the whole chain of regulatory influences brought into play by a local perturbation such as a defect in a cell membrane ion transport protein. To fill this need, we are developing a comprehensive, modular, interactive modeling environment centered on overall regulation of blood pressure and body fluids. We rely on state-of-the-art multi-scale, multi-mode simulation methods. The core model will give succinct input-output (reduced-dimension) descriptions of all relevant organ systems and regulatory processes, and it will be modular, multi-resolution, and extensible, in the sense that detailed sub-modules of any process(es) can be "plugged-in" to the basic model in order to explore, e.g., system-level implications of local perturbations. The goal is to keep the basic core model compact enough to insure fast execution time (in view of eventual use in the clinic) and yet to allow elaborate detailed modules of target tissues or organs in order to focus on the problem area while maintaining the system-level regulatory compensations. We will present the core model, inspired by Guyton's classic 1972 model of overall regulation of blood pressure, and several aspects of the renal, cardiac, and lung modules to be included in the initial development.

Published
2006

44. SAPHIR: a collaborative multi‐scale, multi‐resolution Core Model Environment for the Physiome—with a prototype core model of blood pressure regulation and fluid homeostasis

Author

Thomas, S. Randall, primary, Hannaert, Patrick, additional, Baconnier, Pierre, additional, Fontecave, Julie, additional, Guillaud, François, additional, Le Rolle, Virginie, additional, Maziere, Pierre, additional, Tahi, Fariza, additional, Zehraoui, Farida, additional, Abchiche, Nadia, additional, and Hernandez, Alfredo, additional

Published
2008
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45. SAPHIR - a multi-scale, multi-resolution modeling environment targeting blood pressure regulation and fluid homeostasis

Author

Thomas, S. Randall, primary, Abdulhay, Enas, additional, Baconnier, Pierre, additional, Fontecave, Julie, additional, Francoise, Jean-Pierre, additional, Guillaud, Francois, additional, Hannaert, Patrick, additional, Hernandez, Alfredo, additional, Le Rolle, Virginie, additional, Maziere, Pierre, additional, Tahi, Fariza, additional, and Zehraoui, Farida, additional

Published
2007
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