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Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts

A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or r...

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Autores principales: Hjortbak, Marie V., Jespersen, Nichlas R., Jensen, Rebekka V., Lassen, Thomas R., Hjort, Johanne, Povlsen, Jonas A., Støttrup, Nicolaj B., Hansen, Jakob, Hausenloy, Derek J., Bøtker, Hans Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801421/
https://www.ncbi.nlm.nih.gov/pubmed/33431942
http://dx.doi.org/10.1038/s41598-020-79449-x
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author Hjortbak, Marie V.
Jespersen, Nichlas R.
Jensen, Rebekka V.
Lassen, Thomas R.
Hjort, Johanne
Povlsen, Jonas A.
Støttrup, Nicolaj B.
Hansen, Jakob
Hausenloy, Derek J.
Bøtker, Hans Erik
author_facet Hjortbak, Marie V.
Jespersen, Nichlas R.
Jensen, Rebekka V.
Lassen, Thomas R.
Hjort, Johanne
Povlsen, Jonas A.
Støttrup, Nicolaj B.
Hansen, Jakob
Hausenloy, Derek J.
Bøtker, Hans Erik
author_sort Hjortbak, Marie V.
collection PubMed
description A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia.
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spelling pubmed-78014212021-01-12 Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts Hjortbak, Marie V. Jespersen, Nichlas R. Jensen, Rebekka V. Lassen, Thomas R. Hjort, Johanne Povlsen, Jonas A. Støttrup, Nicolaj B. Hansen, Jakob Hausenloy, Derek J. Bøtker, Hans Erik Sci Rep Article A multitargeted strategy to treat the consequences of ischemia and reperfusion (IR) injury in acute myocardial infarction may add cardioprotection beyond reperfusion therapy alone. We investigated the cardioprotective effect of mild hypothermia combined with local ischemic preconditioning (IPC) or remote ischemic conditioning (RIC) on IR injury in isolated rat hearts. Moreover, we aimed to define the optimum timing of initiating hypothermia and evaluate underlying cardioprotective mechanisms. Compared to infarct size in normothermic controls (56 ± 4%), mild hypothermia during the entire or final 20 min of the ischemic period reduced infarct size (34 ± 2%, p < 0.01; 35 ± 5%, p < 0.01, respectively), while no reduction was seen when hypothermia was initiated at reperfusion (51 ± 4%, p = 0.90). In all groups with effect of mild hypothermia, IPC further reduced infarct size. In contrast, we found no additive effect on infarct size between hypothermic controls (20 ± 3%) and the combination of mild hypothermia and RIC (33 ± 4%, p = 0.09). Differences in temporal lactate dehydrogenase release patterns suggested an anti-ischemic effect by mild hypothermia, while IPC and RIC preferentially targeted reperfusion injury. In conclusion, additive underlying mechanisms seem to provide an additive effect of mild hypothermia and IPC, whereas the more clinically applicable RIC does not add cardioprotection beyond mild hypothermia. Nature Publishing Group UK 2021-01-11 /pmc/articles/PMC7801421/ /pubmed/33431942 http://dx.doi.org/10.1038/s41598-020-79449-x Text en © The Author(s) 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Hjortbak, Marie V.
Jespersen, Nichlas R.
Jensen, Rebekka V.
Lassen, Thomas R.
Hjort, Johanne
Povlsen, Jonas A.
Støttrup, Nicolaj B.
Hansen, Jakob
Hausenloy, Derek J.
Bøtker, Hans Erik
Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_full Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_fullStr Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_full_unstemmed Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_short Cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
title_sort cardioprotective effect of combination therapy by mild hypothermia and local or remote ischemic preconditioning in isolated rat hearts
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801421/
https://www.ncbi.nlm.nih.gov/pubmed/33431942
http://dx.doi.org/10.1038/s41598-020-79449-x
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