Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death
Background Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current...
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| Materiálatiipa: | Artihkal |
| Giella: | English |
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Wiley
2024-04-01
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| Ráidu: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Fáttát: | |
| Liŋkkat: | https://www.ahajournals.org/doi/10.1161/JAHA.123.033503 |
| _version_ | 1826988221307813888 |
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| author | Manuel Egle Natalia Mendez‐Carmona Adrian Segiser Selianne Graf Matthias Siepe Sarah Longnus |
| author_facet | Manuel Egle Natalia Mendez‐Carmona Adrian Segiser Selianne Graf Matthias Siepe Sarah Longnus |
| author_sort | Manuel Egle |
| collection | DOAJ |
| description | Background Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects. Methods and Results Using a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω‐nitro‐L‐arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω‐nitro‐L‐arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω‐nitro‐L‐arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels. Conclusions HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts. |
| first_indexed | 2024-04-24T08:52:18Z |
| format | Article |
| id | doaj.art-8cd6540704ec4cbd927212595a468bbf |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2025-02-18T07:48:24Z |
| publishDate | 2024-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-8cd6540704ec4cbd927212595a468bbf2024-11-05T14:14:55ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-04-0113810.1161/JAHA.123.033503Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory DeathManuel Egle0Natalia Mendez‐Carmona1Adrian Segiser2Selianne Graf3Matthias Siepe4Sarah Longnus5Department of Cardiac Surgery Inselspital, Bern University Hospital, University of Bern SwitzerlandDepartment of Cardiac Surgery Inselspital, Bern University Hospital, University of Bern SwitzerlandDepartment of Cardiac Surgery Inselspital, Bern University Hospital, University of Bern SwitzerlandDepartment of Cardiac Surgery Inselspital, Bern University Hospital, University of Bern SwitzerlandDepartment of Cardiac Surgery Inselspital, Bern University Hospital, University of Bern SwitzerlandDepartment of Cardiac Surgery Inselspital, Bern University Hospital, University of Bern SwitzerlandBackground Cardiac donation after circulatory death is a promising option to increase graft availability. Graft preservation with 30 minutes of hypothermic oxygenated perfusion (HOPE) before normothermic machine perfusion may improve cardiac recovery as compared with cold static storage, the current clinical standard. We investigated the role of preserved nitric oxide synthase activity during HOPE on its beneficial effects. Methods and Results Using a rat model of donation after circulatory death, hearts underwent in situ ischemia (21 minutes), were explanted for a cold storage period (30 minutes), and then reperfused under normothermic conditions (60 minutes) with left ventricular loading. Three cold storage conditions were compared: cold static storage, HOPE, and HOPE with Nω‐nitro‐L‐arginine methyl ester (nitric oxide synthase inhibitor). To evaluate potential confounding effects of high coronary flow during early reperfusion in HOPE hearts, bradykinin was administered to normalize coronary flow to HOPE levels in 2 additional groups (cold static storage and HOPE with Nω‐nitro‐L‐arginine methyl ester). Cardiac recovery was significantly improved in HOPE versus cold static storage hearts, as determined by cardiac output, left ventricular work, contraction and relaxation rates, and coronary flow (P<0.05). Furthermore, HOPE attenuated postreperfusion calcium overload. Strikingly, the addition of Nω‐nitro‐L‐arginine methyl ester during HOPE largely abolished its beneficial effects, even when early reperfusion coronary flow was normalized to HOPE levels. Conclusions HOPE provides superior preservation of ventricular and vascular function compared with the current clinical standard. Importantly, HOPE's beneficial effects require preservation of nitric oxide synthase activity during the cold storage. Therefore, the application of HOPE before normothermic machine perfusion is a promising approach to optimize graft recovery in donation after circulatory death cardiac grafts.https://www.ahajournals.org/doi/10.1161/JAHA.123.033503donation after circulatory deathex vivo/ex situ heart perfusionheart failureheart transplantationhypothermic oxygenated perfusion |
| spellingShingle | Manuel Egle Natalia Mendez‐Carmona Adrian Segiser Selianne Graf Matthias Siepe Sarah Longnus Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease donation after circulatory death ex vivo/ex situ heart perfusion heart failure heart transplantation hypothermic oxygenated perfusion |
| title | Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death |
| title_full | Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death |
| title_fullStr | Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death |
| title_full_unstemmed | Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death |
| title_short | Hypothermic Oxygenated Perfusion Improves Vascular and Contractile Function by Preserving Endothelial Nitric Oxide Production in Cardiac Grafts Obtained With Donation After Circulatory Death |
| title_sort | hypothermic oxygenated perfusion improves vascular and contractile function by preserving endothelial nitric oxide production in cardiac grafts obtained with donation after circulatory death |
| topic | donation after circulatory death ex vivo/ex situ heart perfusion heart failure heart transplantation hypothermic oxygenated perfusion |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.123.033503 |
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