Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD)
Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase. We hypothesized that the DCD-relevant pre-ischemic lactate levels negatively affec...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-06-01
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| Series: | Frontiers in Cardiovascular Medicine |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcvm.2021.669205/full |
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| author | Maria Arnold Maria Arnold Adrian Segiser Adrian Segiser Selianne Graf Selianne Graf Natalia Méndez-Carmona Natalia Méndez-Carmona Maria N. Sanz Maria N. Sanz Rahel K. Wyss Rahel K. Wyss Nina Kalbermatter Nina Kalbermatter Nino Keller Nino Keller Thierry Carrel Thierry Carrel Sarah Longnus Sarah Longnus |
| author_facet | Maria Arnold Maria Arnold Adrian Segiser Adrian Segiser Selianne Graf Selianne Graf Natalia Méndez-Carmona Natalia Méndez-Carmona Maria N. Sanz Maria N. Sanz Rahel K. Wyss Rahel K. Wyss Nina Kalbermatter Nina Kalbermatter Nino Keller Nino Keller Thierry Carrel Thierry Carrel Sarah Longnus Sarah Longnus |
| author_sort | Maria Arnold |
| collection | DOAJ |
| description | Introduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase. We hypothesized that the DCD-relevant pre-ischemic lactate levels negatively affect the post-ischemic functional and mitochondrial recovery in an isolated rat heart model of DCD.Methods: Isolated, working rat hearts underwent 28.5′ of global ischemia and 60′ of reperfusion. Prior to ischemia, hearts were perfused with one of three pre-ischemic lactate levels: no lactate (0 Lac), physiologic lactate (0.5 mM; 0.5 Lac), or DCD-relevant lactate (1 mM; 1 Lac). In a fourth group, an inhibitor of the mitochondrial calcium uniporter was added in reperfusion to 1 Lac hearts (1 Lac + Ru360).Results: During reperfusion, left ventricular work (heart rate-developed pressure product) was significantly greater in 0.5 Lac hearts compared to 0 Lac or 1 Lac. In 1 vs. 0.5 Lac hearts, in parallel with a decreased function, cellular and mitochondrial damage was greater, tissue calcium content tended to increase, while oxidative stress damage tended to decrease. The addition of Ru360 to 1 Lac hearts partially abrogated the negative effects of the DCD-relevant pre-ischemic lactate levels (greater post-ischemic left ventricular work and less cytochrome c release in 1 Lac+Ru360 vs. 1 Lac).Conclusion: DCD-relevant levels of pre-ischemic lactate (1 mM) reduce contractile, cellular, and mitochondrial recovery during reperfusion compared to physiologic lactate levels. Inhibition of mitochondrial calcium uptake during early reperfusion improves the post-ischemic recovery of 1 Lac hearts, indicating calcium overload as a potential therapeutic reperfusion target for DCD hearts. |
| first_indexed | 2024-12-21T02:12:11Z |
| format | Article |
| id | doaj.art-8e63ddca9a93462b8d6b6640f82a0a72 |
| institution | Directory Open Access Journal |
| issn | 2297-055X |
| language | English |
| last_indexed | 2024-12-21T02:12:11Z |
| publishDate | 2021-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cardiovascular Medicine |
| spelling | doaj.art-8e63ddca9a93462b8d6b6640f82a0a722022-12-21T19:19:20ZengFrontiers Media S.A.Frontiers in Cardiovascular Medicine2297-055X2021-06-01810.3389/fcvm.2021.669205669205Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD)Maria Arnold0Maria Arnold1Adrian Segiser2Adrian Segiser3Selianne Graf4Selianne Graf5Natalia Méndez-Carmona6Natalia Méndez-Carmona7Maria N. Sanz8Maria N. Sanz9Rahel K. Wyss10Rahel K. Wyss11Nina Kalbermatter12Nina Kalbermatter13Nino Keller14Nino Keller15Thierry Carrel16Thierry Carrel17Sarah Longnus18Sarah Longnus19Department of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandDepartment of Cardiovascular Surgery, Inselspital, Bern University Hospital, Bern, SwitzerlandDepartment for BioMedical Research, University of Bern, Bern, SwitzerlandIntroduction: Donation after circulatory death (DCD) could substantially improve donor heart availability. In DCD, the heart is not only exposed to a period of warm ischemia, but also to a damaging pre-ischemic phase. We hypothesized that the DCD-relevant pre-ischemic lactate levels negatively affect the post-ischemic functional and mitochondrial recovery in an isolated rat heart model of DCD.Methods: Isolated, working rat hearts underwent 28.5′ of global ischemia and 60′ of reperfusion. Prior to ischemia, hearts were perfused with one of three pre-ischemic lactate levels: no lactate (0 Lac), physiologic lactate (0.5 mM; 0.5 Lac), or DCD-relevant lactate (1 mM; 1 Lac). In a fourth group, an inhibitor of the mitochondrial calcium uniporter was added in reperfusion to 1 Lac hearts (1 Lac + Ru360).Results: During reperfusion, left ventricular work (heart rate-developed pressure product) was significantly greater in 0.5 Lac hearts compared to 0 Lac or 1 Lac. In 1 vs. 0.5 Lac hearts, in parallel with a decreased function, cellular and mitochondrial damage was greater, tissue calcium content tended to increase, while oxidative stress damage tended to decrease. The addition of Ru360 to 1 Lac hearts partially abrogated the negative effects of the DCD-relevant pre-ischemic lactate levels (greater post-ischemic left ventricular work and less cytochrome c release in 1 Lac+Ru360 vs. 1 Lac).Conclusion: DCD-relevant levels of pre-ischemic lactate (1 mM) reduce contractile, cellular, and mitochondrial recovery during reperfusion compared to physiologic lactate levels. Inhibition of mitochondrial calcium uptake during early reperfusion improves the post-ischemic recovery of 1 Lac hearts, indicating calcium overload as a potential therapeutic reperfusion target for DCD hearts.https://www.frontiersin.org/articles/10.3389/fcvm.2021.669205/fullcardiac ischemia reperfusion injurydonation after circulatory deathheart transplantationlactatecontractile function |
| spellingShingle | Maria Arnold Maria Arnold Adrian Segiser Adrian Segiser Selianne Graf Selianne Graf Natalia Méndez-Carmona Natalia Méndez-Carmona Maria N. Sanz Maria N. Sanz Rahel K. Wyss Rahel K. Wyss Nina Kalbermatter Nina Kalbermatter Nino Keller Nino Keller Thierry Carrel Thierry Carrel Sarah Longnus Sarah Longnus Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD) Frontiers in Cardiovascular Medicine cardiac ischemia reperfusion injury donation after circulatory death heart transplantation lactate contractile function |
| title | Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD) |
| title_full | Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD) |
| title_fullStr | Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD) |
| title_full_unstemmed | Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD) |
| title_short | Pre-ischemic Lactate Levels Affect Post-ischemic Recovery in an Isolated Rat Heart Model of Donation After Circulatory Death (DCD) |
| title_sort | pre ischemic lactate levels affect post ischemic recovery in an isolated rat heart model of donation after circulatory death dcd |
| topic | cardiac ischemia reperfusion injury donation after circulatory death heart transplantation lactate contractile function |
| url | https://www.frontiersin.org/articles/10.3389/fcvm.2021.669205/full |
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