Postconditioning by Delayed Administration of Ciclosporin A: Implication for Donation after Circulatory Death (DCD)
| Autor: | René Ferrera, Marie Védère, Megane Lo-Grasso, Lionel Augeul, Christophe Chouabe, Gabriel Bidaux, Delphine Baetz |
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| Přispěvatelé: | Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-18-CE18-0015,LIFEGRAFT,Innovation destinée à diagnostiquer et améliorer la qualité du greffon cardiaque avant transplantation(2018), Ferrera, René, APPEL À PROJETS GÉNÉRIQUE 2018 - Innovation destinée à diagnostiquer et améliorer la qualité du greffon cardiaque avant transplantation - - LIFEGRAFT2018 - ANR-18-CE18-0015 - AAPG2018 - VALID |
| Jazyk: | angličtina |
| Rok vydání: | 2022 |
| Předmět: |
donation after circulatory death (DCD)
heart transplantation ciclosporin A-postconditioning–ischemia reperfusion injury (IRI)-delayed reperfusion-mitochondria-permeability transition pore Mitochondrial Permeability Transition Pore Organic Chemistry Myocardial Reperfusion Injury General Medicine Catalysis Rats Heart Arrest [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Computer Science Applications Inorganic Chemistry Necrosis [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system Cyclosporine Animals Physical and Theoretical Chemistry Molecular Biology Spectroscopy |
| Zdroj: | International Journal of Molecular Sciences; Volume 23; Issue 21; Pages: 12858 International Journal of Molecular Sciences International Journal of Molecular Sciences, 2022, 23 (21), pp.12858. ⟨10.3390/ijms232112858⟩ |
| ISSN: | 1422-0067 1661-6596 |
| DOI: | 10.3390/ijms232112858 |
| Popis: | Heart transplantation is facing a shortage of grafts. Donation after Circulatory Death (DCD) would constitute a new potential of available organs. In the present work, we aimed to evaluate whether Postconditioning (ischemic or with ciclosporin-A (CsA)) could reduce ischemia-reperfusion injury in a cardiac arrest model when applied at the start of reperfusion or after a delay. An isolated rat heart model was used as a model of DCD. Hearts were submitted to a cardiac arrest of 40 min of global warm ischemia (37 °C) followed by 3 h of 4 °C-cold preservation, then 60 min reperfusion. Hearts were randomly allocated into the following groups: control, ischemic postconditioning (POST, consisting of two episodes each of 30 s ischemia and 30 s reperfusion at the onset of reperfusion), and CsA group (CsA was perfused at 250 nM for 10 min at reperfusion). In respective subgroups, POST and CsA were applied after a delay of 3, 10, and 20 min. Necrosis was lower in CsA and POST versus controls (p < 0.01) whereas heart functions were improved (p < 0.01). However, while the POST lost its efficacy if delayed beyond 3 min of reperfusion, CsA treatment surprisingly showed a reduction of necrosis even if applied after a delay of 3 and 10 min of reperfusion (p < 0.01). This cardioprotection by delayed CsA application correlated with better functional recovery and higher mitochondrial respiratory index. Furthermore, calcium overload necessary to induce mitochondrial permeability transition pore (MPTP) opening was similar in all cardioprotection groups, suggesting a crucial role of MPTP in this delayed protection of DCD hearts. |
| Databáze: | OpenAIRE |
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